Publications

European Network of Pregnancy Registers in Rheumatology (EuNeP)-an overview of procedures and data collection

Abstract (Expand)

BACKGROUND: The collaborative initiative of the European Network of Pregnancy Registers in Rheumatology (EuNeP) aims to combine data available in nationwide pregnancy registers to increase knowledge … on pregnancy outcomes in women with inflammatory rheumatic diseases (IRD) and on drug safety during pregnancy and lactation. The objective of this study was to describe the similarities and differences of the member registers. METHODS: From all registers, information about their structure and design was collected, as well as which parameters regarding demographics, maternal outcomes, treatment, course and outcome of pregnancy, and development of the child were available in the respective datasets. Furthermore, the current recruitment status was reported. RESULTS: The four registers (EGR2 (France), RePreg (Switzerland), RevNatus (Norway), and Rhekiss (Germany)) collect information prospectively and nationwide. Patients can be enrolled before conception or during pregnancy. To date, more than 3500 patients in total have been included, and data on 2200 pregnancies with an outcome are available. The distribution of diagnoses in the respective registers varies considerably, and only three entities (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) are captured by all the registers. Broad consistency was found in non-disease-specific data items, but differences regarding instruments and categories as well as frequency of data collection were revealed. Disease-specific data items are less homogeneously collected. CONCLUSION: Although the registers in this collaboration have similar designs, we found numerous differences in the variables collected. This survey of the status quo of current pregnancy registers is the first step towards identifying data collected uniformly across registers in order to facilitate joint analyses. TRIAL REGISTRATION: Not applicable.

Authors: Y. Meissner, A. Strangfeld, N. Costedoat-Chalumeau, F. Forger, D. Goll, A. Molto, R. Ozdemir, M. Wallenius, R. Fischer-Betz

Date Published: 2019

Publication Type: Journal

Pregnancy and neonatal outcomes in women with axial spondyloarthritis: pooled data analysis from the European Network of Pregnancy Registries in Rheumatology (EuNeP)

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OBJECTIVE: To investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology. METHODS: Prospectively … followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed. RESULTS: In a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points. CONCLUSIONS: Pooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

Authors: Y. Meissner, A. Strangfeld, A. Molto, F. Forger, M. Wallenius, N. Costedoat-Chalumeau, H. Bjorngaard, M. Couderc, R. M. Flipo, G. Guettrot-Imbert, I. Haase, B. Jakobsen, H. S. S. Koksvik, C. Richez, J. Sellam, A. Weiss, A. Zbinden, R. Fischer-Betz, P. collaborator group EuNe

Date Published: 2022

Publication Type: Journal

Mobile Responsive App-A Useful Additional Tool for Data Collection in the German Pregnancy Register Rhekiss?

Abstract (Expand)

Background: The German pregnancy register Rhekiss is designed as a nationwide, web-based longitudinal observational cohort established in 2015. The register follows women with inflammatory rheumatic … disease prospectively from child wish or early pregnancy until 2 years post-partum. Information on clinical and laboratory parameters, drug treatment, and (adverse) pregnancy outcomes are documented in pre-specified intervals. Physicians and patients report data for the same time periods via separated accounts and forms into a web-based application (app). As data entry on mobile devices might improve response rates of patients, a responsive app as a further convenient documentation option was developed. Methods: The Rhekiss-app is available for self-reported data retrieval since August 2017 from the App stores. For the current analysis, Rhekiss register data were used from the start of the register until 30 September 2020. The analyses were performed for forms containing information on devices. Outcome parameters were compared for mobile and desktop users for the quantity and quality of filled forms. Results: In total, 5,048 forms were received and submitted by 966 patients. About 57% of forms were sent from mobile devices with the highest numbers in patients with child wishes (63%). Users of mobile devices were slightly younger and often had less high-education level (62 vs. 79%) compared with desktop users. The proportion of forms submitted via mobile devices increased steadily from 48% in the fourth quarter of 2018 to 64% in the third quarter of 2020. The proportion of forms received before and after the Rhekiss-app implementation increased with the highest increase of 12% for forms filled at time point 12 months post-partum. Mobile users submitted significantly more forms than desktop users (2.9 vs. 2.1), data sent via desktops were more often complete (88 vs. 86%). Conclusion: The responsive app is a valuable additional tool for data collection and is well-accepted by patients as indicated by its increasing use in Rhekiss. Apart from desktop/browser developments, the technological adoptions within observational cohorts and registries should take smartphone requirements and developments into account, especially when patient-reported data in young, mobile patients are collected, bearing in mind that data quality could be compromised and concepts for improving data quality should be implemented.

Authors: J. G. Richter, A. Weiss, C. Bungartz, R. Fischer-Betz, A. Zink, M. Schneider, A. Strangfeld

Date Published: 2021

Publication Type: Journal

Rhekiss-The German Register for Child Wish and Pregnancies in Inflammatory Rheumatic Diseases

Abstract (Expand)

In pharmacoepidemiology, robust data are needed to judge the impact of drug treatment on pregnancy, pregnancy outcomes and breast-fed infants. As pregnant and breastfeeding women are usually excluded … from randomised clinical trials, observational studies are required. One of those data sources are pregnancy registers specifically developed to focus on certain diseases or disease groups. The German Rhekiss register investigates pregnancies in women with chronic inflammatory rheumatic diseases (IRD). Rhekiss is a nationwide, multicentre, longitudinal study, in which women aged 18 years or older with an underlying IRD can be enrolled by a rheumatologist either when planning a pregnancy or in the first half of pregnancy. Data are collected prospectively at regular follow-up visits. Rheumatologists and patients provide information in a web-based system before conception (if enrolment was at the time of pregnancy planning), during and after pregnancy. A smartphone app is available for patients. Maternal and clinical information, general laboratory markers, treatment with antirheumatic and other drugs, adverse events, items related to course and outcome of pregnancy and the health of the child are uniformly assessed for all diseases. Individual information on the IRD includes classification criteria, diagnosis-specific laboratory parameters, clinical parameters and validated instruments to measure disease activity or damage. Furthermore, patient-reported outcome measures are captured. A total of 2013 individual patients have been enrolled in the register, and data on 1801 completed pregnancies are available. In summary, Rhekiss is a comprehensive and complex register that can answer various research questions about pregnancy in women with chronic IRDs.

Authors: A. Strangfeld, Y. Meissner, A. Weiss, T. Rudi, A. Zink, T. Ellmann, T. Filla, P. Aries, X. Baraliakos, C. Bungartz, C. Glaser, J. Henes, H. M. Lorenz, M. Schneider, S. Spathling-Mestekemper, C. Specker, J. G. Richter, R. Fischer-Betz

Date Published: 2024

Publication Type: Journal

[Comparative evaluation of a German version of the Health Assessment Questionnaire and the Hannover Functional Capacity Questionnaire]

Abstract (Expand)

OBJECTIVE: To translate the Health Assessment Questionnaire Disability Index (HAQ) into a German version, to validate and to compare its properties with two different versions of the Hannover Functional … Ability Questionnaire (HFAQ) in a German speaking population. METHODS: The test-retest reliability was tested by Pearson correlation in 32 outpatients of the Department of Rheumatology of the Medizinische Hochschule Hannover. For retesting, the questionnaire was mailed to them 1 week later. To validate the questionnaire it was administered to 110 inpatients in three different hospitals. All patients fulfilled the American College of Rheumatology 1987 revised criteria of rheumatoid arthritis (RA) or the Rome criteria of definitive inactive RA. The internal consistency was measured by Cronbach’s coefficient alpha (CCA). To assess criterion validity we compared the HAQ and the two versions of the HFAQ with Keitel’s test (KT) and the modified Steinbrocker classification (mSC). Construct validity was assessed by comparing these instruments with different clinical and laboratory variables. A multivariate analysis was used to identify the most important factors that are influencing the HAQ- and HFAQ-scores. RESULTS: Test-retest reliability of the HAQ was r = 0.94. CCA was 0.91 (HAQ), 0.90 (HFAQ-P) and 0.93 (HFAQ-PR). The KT Pearson correlation coefficients reached r = -0.73 (HAQ), r = +0.74 (HFAQ-P) and r = +0.71 (HFAQ-PR). The mSC correlated r = +0.75 (HAQ), r = -0.72 (HFAQ-P) and r = -0.70 (HFAQ-PR). The correlation coefficients of HAQ/HFAQ-P was r = -0.87 and of HAQ/HFAQ-PR r = -0.88. The correlations between other clinical and laboratory variables reached from r = +/-0.58 (pain/HAQ) to r = +/-0.11 (number of swollen joints/HFAQ-PR). In backward multiple regression analysis 59-64% of the variance of disability measured by the questionnaires was explained predominantly by pain (32-33%) and by range of motion (16-21%). CONCLUSION: The German version of the HAQ presented here and the two versions of the HFAQ are reliable and valid instruments for measuring functional disability in a German-speaking population with RA. The construct measured by the HAQ and both versions of the HFAQ showed a high degree of correspondence.

Authors: J. Lautenschlager, W. Mau, T. Kohlmann, H. H. Raspe, F. Struve, W. Bruckle, H. Zeidler

Date Published: 1997

Publication Type: Misc

[Contribution of databases to regional and supra-regional quality improvement in rheumatologic treatment and patient management. Professional Society of Regional Cooperative Rheumatic Disease Centers]

Abstract (Expand)

The uniform database of the German Collaborative Arthritis Centers is an important instrument for health services research, the observation of outcomes of daily rheumatological care, and for quality … assessment in rheumatology. Deficits concerning modern medical and comprehensive therapy in non-specialized outpatient care were shown. The data give evidence of the benefits of the initiation of rheumatological care. Data of practice variation in rheumatology are used for internal quality assessment.

Author: A. Zink

Date Published: 1998

Publication Type: Journal

The national database of the German Collaborative Arthritis Centres: I. Structure, aims, and patients

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OBJECTIVE: To describe the aims, principles, and content of the German rheumatological database and to present data on patient mix and healthcare provision for the year 1998. METHODS: The German … rheumatological database contains clinical and patient derived data of the outpatients with inflammatory rheumatic diseases seen at one of the 24 collaborative arthritis centres. The case mix, institutional context, and demographic features of 25 653 patients from the year 1998 were analysed. RESULTS: 51% of the patients had rheumatoid arthritis, 23% seronegative spondyloarthropathies, including ankylosing spondylitis, psoriatic arthritis, and reactive arthritis, and 19% had vasculitis, including SLE (5%). The distribution of the age at onset of patients with RA with < or = 2 years’ disease duration was comparable with recent incidence data from population studies. The case mix differed between university departments and rheumatology hospitals as well as individual practices. 65% of the male and 46% of the female patients at ages 18-60 were still in gainful employment, the rates of employment were 14% below the population rates for women, and 11% below those for men. 62% of all patients had seen a rheumatologist within the first year of disease, 73% within the first two years. Ankylosing spondylitis was seen in rheumatological care much later than all other diseases (only 39% within the first year). The mean number of contacts with a rheumatologist was five a year; rheumatologists in individual practices saw their patients seven times a year on the average. Together with visits to the non-specialist doctor mainly treating the patient, the mean number of visits to the doctor for a rheumatic condition was 20 a year. CONCLUSION: Large databases like this one give information about the patient case mix in different healthcare settings, about treatment practice, and about the consequences of disease. Patients treated in specialised rheumatology units in Germany are referred earlier than in the past, which probably reflects better regional cooperation due to the implementation of arthritis centres. University departments and outpatient clinics of rheumatology hospitals contribute considerably to the specialised care of patients with arthritis and connective tissue diseases.

Authors: A. Zink, J. Listing, C. Klindworth, H. Zeidler, Centres German Collaboratrive Arthritis

Date Published: 2001

Publication Type: Journal

The national database of the German Collaborative Arthritis Centres: II. Treatment of patients with rheumatoid arthritis

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OBJECTIVE: To describe current treatment of patients with rheumatoid arthritis (RA) in German rheumatology. METHODS: Data from the German rheumatological database of 1998, comprising clinical and patient … questionnaire data of 12 992 outpatients with RA seen at 24 collaborative arthritis centres in Germany, were analysed. RESULTS: At the time of documentation, 88% of the patients with RA were undergoing disease modifying antirheumatic drug (DMARD) treatment. Methotrexate (MTX) was prescribed to 56% of the patients (61% with seropositive and 45% with seronegative RA). Combination treatment was used in 15%. MTX was the drug of first choice even in patients with up to one year’s disease duration (49%), followed by antimalarial drugs (21%). Patients treated by non-rheumatologists within the previous year had received DMARD treatment in only 33% of the cases. In steroid treatment, low doses (< or = 7.5 mg/day) were used by rheumatologists much more often (44%) than higher doses (12%). 16% of the patients had been inpatients during the previous year, with a median length of stay accumulated over the year of 21 days. Together with stays in inpatient rehabilitation, 22% of all patients had had some form of inpatient treatment. Comprehensive measures such as occupational therapy and patient education were prescribed to fewer than 12% of the patients, mostly during their hospital stay. CONCLUSION: German rheumatologists do follow recent recommendations about early and effective treatment. However, there are still deficits in outpatient care with non-medicinal measures like occupational therapy and patient education, which may partly explain the high hospital admission rates.

Authors: A. Zink, J. Listing, M. Niewerth, H. Zeidler, Centres German Collaborative Arthritis

Date Published: 2001

Publication Type: Journal

Practice variation in the treatment of rheumatoid arthritis among German rheumatologists

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OBJECTIVE: To describe practice variation in the treatment of rheumatoid arthritis (RA) among German rheumatologists with regard to drug and non-drug therapy. METHODS: We used data of 7,326 patients … with RA registered in a national German rheumatological database in 1998. In the database, every patient with an inflammatory rheumatic disease seen at one of the German Collaborative Arthritis Centres is registered once a year with a standard clinical data form and a patient questionnaire. We compared health care provided by 29 rheumatological outpatient units. For drug and non-drug treatment unit prescription rates, ranges and outliers were calculated. Logistic regression analysis was used for case mix adjustment and for the identification of practice patterns. RESULTS: We observed variation concerning the frequency of use of single disease modifying antirheumatic drugs (DMARD). The median of the prescription rates in the 29 units for methotrexate (MTX) was 55% in 1998 (1st quartile: 51%, 3rd quartile: 63%); sulfasalazine had a median of 15% (quartiles: 10%/19%), antimalarials a median of 8% (quartiles: 5%/21%). Combination DMARD therapy was used in 11% (quartiles: 6%/18%). Prescriptions of low dose steroids (< or = 7.5 mg) had a median of 45% (quartiles: 35%/55%), and nonsteroidal antiinflammatory drugs (NSAID) had a median prescription rate of 58% (quartiles: 50%/70%). High variation was also found concerning active physiotherapy (median: 41%; quartiles 34%/55%) and passive physical measures (median 14%, quartiles 9%/37%). Differences in case mix (age, sex, rheumatoid factor, disease duration, severity, disability) only explained a small proportion of the total variation. When the units were grouped according to the frequency of prescription of DMARD combination therapy, treatment patterns could be identified. Units with higher rates of DMARD combination therapy used more drugs for the prevention and treatment of osteoporosis, more active physiotherapy but fewer NSAID and fewer passive physical therapies. CONCLUSION: Variation in drug and non-drug treatment indicates significant differences in health care provision. Trends in the drug management of RA are adopted differentially by the members of the rheumatology community. The large variability in non-drug therapies may, apart from differences in availability, suggest a lack of agreement on therapeutic effectiveness.

Authors: A. Zink, J. Listing, S. Ziemer, H. Zeidler, Centres German Collaborative Arthritis

Date Published: 2001

Publication Type: Journal

Health care and burden of illness in systemic lupus erythematosus compared to rheumatoid arthritis: results from the National Database of the German Collaborative Arthritis Centres

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During the past 20 years, outcome studies in the rheumatic diseases have, on the one hand, given increasing evidence of the unfavourable long-term prognosis of rheumatoid arthritis (RA) and on the other … hand determined continuous improvement of prognosis in systemic lupus erythematosus (SLE). The aim of the study was to investigate how this translates into the current spectrum of patients with rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) seen by rheumatologists in Germany and to compare aspects of the burden of disease, disease outcomes and treatment between these two important rheumatic diseases using a large clinical database. Current health care was analysed with data from the German rheumatological database of 10 068 patients with RA and 1248 patients with SLE seen by rheumatologists in 2001. In addition, of a total of 3546 patients with SLE and 24 969 patients with RA seen at the German Collaborative Arthritis Centres between 1994 and 2001, 3465 cases of SLE were matched by age, sex, disease duration and referral status with a corresponding RA case. There were considerable differences in treatment of patients before referral to a rheumatologist and in rheumatologic care. In 2001, patients with SLE were treated by their rheumatologists mainly with antimalarials (AM, 37%), azathioprine (29%) and nonselective NSAIDs (16%). Of them, 61% received at least one immunosuppressive drug (including AM) plus glucocorticoids. In RA, methotrexate was the predominant medication (63%), and 56% received at least one immunosuppressive drug plus glucocorticoids. Matched pairs analysis showed that SLE patients with a short disease duration were almost equally burdened by pain, functional limitations and reduced health status as RA patients. After a disease duration of >10 years, however, patients with RA showed poorer outcomes than those with SLE: RA patients reported significantly more often severe pain (30% in RA versus 17% in SLE) and poor global health status (52 versus 38%), and their disease activity as well as severity was rated higher by the rheumatologists. In conclusion, comparing large groups of RA and SLE patients we found a similar burden in early but not in late disease. Taking into account limitations as to the generalizability of the results (recruitment in rheumatologic care, cross-sectional data, underestimation of SLE-specific outcomes), the discrepancy between the high increase in disease-related negative outcomes with longer disease duration in RA but not in SLE indicates a better long-term prognosis in SLE concerning the items observed. The great disparity in treatment intensity between rheumatologists and nonrheumatologists shows that the involvement of a specialist is needed equally in both diseases.

Authors: A. Zink, R. Fischer-Betz, K. Thiele, J. Listing, D. Huscher, E. Gromnica-Ihle, C. Specker, M. Schneider, Centers German Collaborative Arthritis

Date Published: 2004

Publication Type: Journal

Employment across chronic inflammatory rheumatic diseases and comparison with the general population

Abstract (Expand)

OBJECTIVE: To compare labor force participation across chronic inflammatory rheumatic diseases in order to assess the influence of the disease, disease duration, sex, education, and labor market … conditions on employment. METHODS: Data from the German rheumatological database on outpatients of working age (20-59 yrs) between 1993 and 2001 were analyzed. The patients had rheumatoid arthritis (RA; n = 26,071), ankylosing spondylitis (AS; n = 5564), psoriatic arthritis (PsA; n = 6041), systemic lupus erythematosus (SLE; n = 4603), systemic sclerosis (SSc; n = 802), or Wegener’s granulomatosis (WG; n = 385). Using population data, standardized employment ratios (SER) and part-time employment ratios of observed versus expected cases with 95% CI were calculated by means of indirect standardization for age and year of documentation. RESULTS: Across all diseases the overall employment rates were significantly lower than in the general population. Significant differences in SER were found between the diseases. The lowest SER of 0.76 to 0.81 (1.0 = population) were found in patients with RA, SLE, SSc, and WG. Higher SER were seen in AS (0.94) and PsA (0.92). In patients with a disease duration > 10 years the relative risk of being employed compared to RA, was 1.42 for AS, 1.26 for PsA, and 1.15, 1.03, 0.62 for PsA, SLE, SSc and WG, respectively. Comparing areas with low and high unemployment rates, a highly significant influence of labor market conditions on the SER was observed. The SER were significantly lower in patients with < 10 years of school education. CONCLUSION: Differences between employment rates in the population and the rates for the diseases under study are smaller than assumed by most clinical studies, especially in AS and PsA. However, these differences increase with longer disease duration. Specific measures to prevent patients from losing their job are needed, especially in areas with overall high unemployment.

Authors: W. Mau, J. Listing, D. Huscher, H. Zeidler, A. Zink

Date Published: 2005

Publication Type: Journal

Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data

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OBJECTIVES: Implementation of the International Statistical Classification of Disease and Related Health Problems, 10th Revision (ICD-10) coding system presents challenges for using administrative data. … Recognizing this, we conducted a multistep process to develop ICD-10 coding algorithms to define Charlson and Elixhauser comorbidities in administrative data and assess the performance of the resulting algorithms. METHODS: ICD-10 coding algorithms were developed by "translation" of the ICD-9-CM codes constituting Deyo’s (for Charlson comorbidities) and Elixhauser’s coding algorithms and by physicians’ assessment of the face-validity of selected ICD-10 codes. The process of carefully developing ICD-10 algorithms also produced modified and enhanced ICD-9-CM coding algorithms for the Charlson and Elixhauser comorbidities. We then used data on in-patients aged 18 years and older in ICD-9-CM and ICD-10 administrative hospital discharge data from a Canadian health region to assess the comorbidity frequencies and mortality prediction achieved by the original ICD-9-CM algorithms, the enhanced ICD-9-CM algorithms, and the new ICD-10 coding algorithms. RESULTS: Among 56,585 patients in the ICD-9-CM data and 58,805 patients in the ICD-10 data, frequencies of the 17 Charlson comorbidities and the 30 Elixhauser comorbidities remained generally similar across algorithms. The new ICD-10 and enhanced ICD-9-CM coding algorithms either matched or outperformed the original Deyo and Elixhauser ICD-9-CM coding algorithms in predicting in-hospital mortality. The C-statistic was 0.842 for Deyo’s ICD-9-CM coding algorithm, 0.860 for the ICD-10 coding algorithm, and 0.859 for the enhanced ICD-9-CM coding algorithm, 0.868 for the original Elixhauser ICD-9-CM coding algorithm, 0.870 for the ICD-10 coding algorithm and 0.878 for the enhanced ICD-9-CM coding algorithm. CONCLUSIONS: These newly developed ICD-10 and ICD-9-CM comorbidity coding algorithms produce similar estimates of comorbidity prevalence in administrative data, and may outperform existing ICD-9-CM coding algorithms.

Authors: H. Quan, V. Sundararajan, P. Halfon, A. Fong, B. Burnand, J. C. Luthi, L. D. Saunders, C. A. Beck, T. E. Feasby, W. A. Ghali

Date Published: 2005

Publication Type: Journal

[Prescription of glucocorticoids by rheumatologists in patients with rheumatoid arthritis in Germany]

Abstract (Expand)

Systemic GCs are among the most important therapeutic options in modern rheumatology. Due to their fast clinical effects and their high anti-inflammatory potential, they are indispensable in a large … number of cases. This applies despite the well-known spectrum of adverse events and despite limited evidence from randomized clinical trials. In this situation, the results of observational studies gain additional importance. They provide information on therapeutic decisions of rheumatologists concerning GC therapy and their combination with other drugs as well as concerning the prevention of adverse events such as GC induced osteoporosis. The data gathered in the national database of the German Collaborative Arthritis Centers show that at the time of documentation 60% of all RA patients were under therapy with GCs, 85% of these were treated with a dosage of up to 7.5 mg/d. GCs are especially frequently used in combination with new or highly potent DMARDs. This underlines that rheumatologists take activity and severity into account in deciding both about GCs and DMARDs. However, there is high practice variation regarding the frequency of GC use among the rheumatological facilities which demonstrates the lack of good evidence.Rheumatologists are aware of various patient risks when prescribing GCs and adapt their therapies to these risks. Two thirds of all patients under GCs were receiving therapy for the prevention or treatment of osteoporosis at documentation, high risk groups such as women over 50 even more frequently. The data emphasize the high importance of GCs in modern rheumatology.

Authors: K. Thiele, F. Buttgereit, D. Huscher, A. Zink, Rheumazentren Arbeitsgemeinschaft Regionaler Kooperativer

Date Published: 2005

Publication Type: Journal

Current use of glucocorticoids in patients with rheumatoid arthritis in Germany

Abstract (Expand)

OBJECTIVE: To describe the current use of glucocorticoids in German patients with rheumatoid arthritis (RA). METHODS: We analyzed clinical and patient-derived data from 10,068 outpatients with RA from … the national database of the German Collaborative Arthritis Centres for the year 2001 collected by more than 80 rheumatologists in hospitals and private practices. RESULTS: Systemic glucocorticoid therapy was prescribed for 60% of all patients with RA in rheumatologic care. The proportion of patients receiving systemic glucocorticoids in addition to disease-modifying antirheumatic drug (DMARD) therapy ranged from 53% to 81% of the patients for the various DMARDs. Glucocorticoid therapy was administered more often in combination with tumor necrosis factor inhibitors (81%), cyclosporin A (80%), or leflunomide (77%) than with more traditional DMARDs such as methotrexate (63%) or sulfasalazine (55%). Regarding the prevention and treatment of osteoporosis, 63% of patients taking systemic glucocorticoids were also receiving some type of osteoporosis therapy, as opposed to only 26% of those not taking glucocorticoids. CONCLUSION: Glucocorticoids play a pivotal role in the management of RA. This is reflected in the extensive use of low-dose glucocorticoids by German rheumatologists. Even if highly effective DMARDs are prescribed, they are accompanied by glucocorticoids, at least in the initial phase. High-dose glucocorticoids are prescribed for only a small proportion of the patients. There is increasing awareness of the risk of osteoporosis in long-term glucocorticoid treatment, demonstrated by the fact that osteoporosis medication is prescribed for a large proportion of patients taking glucocorticoids.

Authors: K. Thiele, F. Buttgereit, D. Huscher, A. Zink, Centres German Collaborative Arthritis

Date Published: 2005

Publication Type: Journal

Cost of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and systemic lupus erythematosus in Germany

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OBJECTIVE: To estimate and compare the direct and indirect costs of illness in rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis (PsA) and systemic lupus erythematosus (SLE), and to … evaluate the effect of sex, disease duration and functional status on the various cost domains. METHODS: Data of outpatients, aged 18-65, with rheumatoid arthritis (n = 4351), ankylosing spondylitis (n = 827), PsA (n = 908) or SLE (n = 844), who were enrolled in the national database of the German collaborative arthritis centres in 2002, were analysed. Data on healthcare consumption, out-of-pocket expenses and productivity losses were derived from doctors and patients. For the calculation of indirect costs, the human capital approach (HCA) and the friction cost approach (FCA) were applied. RESULTS: Mean direct costs amounted to 4737 euros a year in rheumatoid arthritis, 3676 euros in ankylosing spondylitis, 3156 euros in PsA and 3191 euros in SLE. By using the HCA, total costs were calculated at 15,637 euros in rheumatoid arthritis, 13,513 euros in ankylosing spondylitis, 11,075 euros in PsA and 14,411 euros in SLE, whereas with the FCA the numbers were 7899 euros, 7204 euros, 5570 euros and 6518 euros, respectively. Costs increased with disease duration and were strongly dependent on functional status. In patients with the highest disability (<50% of full function), the total costs on applying the HCA were 34,915 euros in rheumatoid arthritis, 29,647 euros in alkylosing spondylitis, 37,440 euros in PsA and 32,296 euros in SLE. CONCLUSION: The costs of illness are high in all four diseases, with a strong effect of functional status on total costs. Indirect costs differ by the factor 3, based on whether the HCA or the FCA is used.

Authors: D. Huscher, S. Merkesdal, K. Thiele, H. Zeidler, M. Schneider, A. Zink, Centres German Collaborative Arthritis

Date Published: 2006

Publication Type: Journal

[The National Database of the German Arthritis Centres–a 12 year balance]

Abstract (Expand)

The National Database of the German Collaborative Arthritis Centres is the most important source for the evaluation of current health care for German rheumatology patients. Since 1993, all outpatients … with inflammatory rheumatic diseases treated in one of 24 arthritis centres have been recorded once a year using a clinical record form and a patient questionnaire. The aim is to gain knowledge on the outcomes and the medical, social and economic consequences of inflammatory rheumatic diseases in the real world, and to monitor continuously the current state and trends in health care. Data from more than 200,000 patients with inflammatory rheumatic diseases from 11 years (1993-2003) are available, making it possible to analyse even very rare diseases with a sufficient numbers of cases. Selected results on the health care situation, practice variation in rheumatology and the burden of illness in various diseases are reported.

Authors: A. Zink, D. Huscher, M. Schneider

Date Published: 2006

Publication Type: Journal

Healthcare and burden of disease in psoriatic arthritis. A comparison with rheumatoid arthritis and ankylosing spondylitis

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OBJECTIVE: To compare quality of life and treatment among patients with psoriatic arthritis (PsA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS) treated by German rheumatologists. METHODS: … Data for outpatients with PsA (n = 1863), RA (n = 9627), or AS (n = 1378) enrolled in the national database of the German collaborative arthritis centers in the year 2002 were analyzed. Among those with PsA, 2 subgroups with predominantly peripheral arthritis (n = 1612) and predominantly axial disease (n = 251) were distinguished. RESULTS: We found a high burden of illness in patients with PsA treated by rheumatologists. Among the 2 subgroups, those with axial PsA had worse outcomes (pain, function) than those with peripheral PsA. However, compared with RA and AS, physician ratings of disease activity and severity were lower in PsA. Concerning access to rheumatology care, there were similarities between AS and axial PsA, with very long disease duration at first visit (mean of about 6 yrs), versus RA and peripheral PsA, with shorter duration (1.6 and 2.5 yrs, respectively). A majority (84%) of patients with PsA were treated with disease modifying antirheumatic drugs. Thirty percent of the patients with PsA currently were under therapy with glucocorticoids, mainly (89%) with a dose < 7.5 mg. CONCLUSION: Patients with PsA seen in rheumatologic care have a burden of illness comparable to that of patients with RA or AS.

Authors: A. Zink, K. Thiele, D. Huscher, J. Listing, J. Sieper, A. Krause, E. Gromnica-Ihle, U. von Hinueber, S. Wassenberg, E. Genth, M. Schneider, Centres German Collaborative Arthritis

Date Published: 2006

Publication Type: Journal

[Validation of secondary data. Strengths and limitations]

Abstract (Expand)

Medical records databases (such as the General Practice Research Database-GPRD) and administrative databases (such as German Statutory Health Insurance (SHI) claims data) are useful sources for … pharmacoepidemiology and health services research. However, these data are not primarily collected for research purposes. Validation studies are needed to examine their completeness and accuracy depending on the corresponding research question. This article reviews strategies for checks of internal consistency within the data from one SHI as well as between data from several SHIs and possibilities of internal data validation. Descriptive analyses of consistency can help to determine the integrity of data. The aim of internal validation is to separate uncertain from true cases based on information from secondary data alone or to reproduce known associations within the database. In addition external validation of secondary data is desirable using original prescriptions, medical records, hospital discharge letters and/or patient or physician interviews as a gold standard. A considerable number of external validation studies of diagnostic coding have been conducted within the GPRD. In contrast, such validation studies of German SHI claims data are mostly lacking and are urgently needed in the near future.

Authors: F. Hoffmann, F. Andersohn, K. Giersiepen, E. Scharnetzky, E. Garbe

Date Published: 2008

Publication Type: Journal

[Burden of illness. First routine report on socio-medical consequences of inflammatory rheumatic disease in Germany]

Abstract (Expand)

A synopsis of different socio-medical consequences of inflammatory rheumatic diseases is not yet available for Germany. Therefore, the data reported during the past decade for rheumatoid arthritis, … ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematodes, and Wegener’s granulomatosis are summarized in this article. Apart from clinical studies, relevant data sources were the national data base of the German collaborative arthritis centres, statistical figures from the compulsory health insurance and the national pension insurance scheme. Data were mainly available for sick leave and work disability showing limitations, which frequently occurred during the early course of diseases and increased with disease duration. Furthermore, different risk factors were identified. Measures to maintain continued participation in the labour force, such as part-time employment, partial work disability instead of full work disability, were not being adequately utilized. Only few data regarding the need of help and care were available. The proportion of patients in need of help and care increased with the duration of rheumatoid arthritis to more than 50% after more than 2 decades. This review presents detailed information concerning aspects of the burden of rheumatic diseases, which are frequently not adequately taken into account. They may be useful for the advice and care of individual patients as well as for decision processes concerning the health care system.

Authors: W. Mau, W. Beyer, I. Ehlebracht-Konig, M. Engel, E. Genth, B. Greitemann, W. H. Jackel, A. Zink

Date Published: 2008

Publication Type: Journal

[Rheumatoid arthritis in the elderly]

Abstract

Not specified

Authors: D. Huscher, C. Sengler, S. Ziegler, E. Gromnica-Ihle

Date Published: 2009

Publication Type: Journal

Dose-related patterns of glucocorticoid-induced side effects

Abstract (Expand)

OBJECTIVE: To identify patterns of self-reported health problems relating to dose and duration of glucocorticoid intake in unselected patients with rheumatoid arthritis from routine practice. METHODS: … Data from 1066 patients were analysed. The clinical status and drug treatment were reported by the physician, health problems during the past 6 months by the patient using a comprehensive list of symptoms. Patients with ongoing glucocorticoid treatment for more than 6 months and current doses of less than 5, 5-7.5 and over 7.5 mg/day prednisone equivalent were compared with a group without any glucocorticoid treatment for at least 12 months. RESULTS: The frequency of self-reported health problems was lowest in the group without glucocorticoid exposition and increased with dosage. Two distinct dose-related patterns of adverse events were observed. A "linear" rising with increasing dose was found for cushingoid phenotype, ecchymosis, leg oedema, mycosis, parchment-like skin, shortness of breath and sleep disturbance. A "threshold pattern" describing an elevated frequency of events beyond a certain threshold value was observed at dosages of over 7.5 mg/day for glaucoma, depression/listlessness and increase in blood pressure. Dosages of 5 mg/day or more were associated with epistaxis and weight gain. A very low threshold was seen for eye cataract (<5 mg/day). CONCLUSION: The associations found are in agreement with biological mechanisms and clinical observations. As there is a paucity of real-life data on adverse effects of glucocorticoids prescribed to unselected groups of patients, these data may help the clinician to adapt therapy with glucocorticoids accordingly and improve the benefit-risk ratio.

Authors: D. Huscher, K. Thiele, E. Gromnica-Ihle, G. Hein, W. Demary, R. Dreher, A. Zink, F. Buttgereit

Date Published: 2009

Publication Type: Journal

Advance and unmet need of health care for patients with rheumatoid arthritis in the German population–results from the German Rheumatoid Arthritis Population Survey (GRAPS)

Abstract (Expand)

OBJECTIVES: To assess the quality of health care for RA patients in the general population of Germany. METHODS: A three-stage population survey was conducted to identify individuals with RA using a … health care access panel (18-79 years; n = 70,112). A 20-item postal screening questionnaire of musculoskeletal symptoms and diagnoses was followed by a detailed questionnaire for those who indicated the possibility of having RA. Respondents who fulfilled the modified ACR decision tree, who reported an RA diagnosis, care by a rheumatologist or the use of DMARDs were asked to participate in a clinical examination by rheumatologists who diagnosed the participants and rated the adequacy of treatment. RESULTS: RA could not be ruled out in 1177 cases, of which 643 agreed to participate in the clinical examination, which was finally attended by 317 participants. Attendees did not differ with regard to any health or treatment measure from those who did not attend. Forty-one RA patients were detected. Of them, 93% had seen a rheumatologist at least once and 63% within the last 12 months. A total of 73% had received DMARD therapy at some time and 59% were currently receiving it. An unmet need for DMARDs was discovered in 29% of the RA attendees. It pertained almost exclusively to the seronegative cases of which 29% had a need to start and 17% to increase a DMARD therapy according to the opinion of the examining rheumatologist. CONCLUSION: Health care for RA patients has improved significantly since the last German RA survey in 1989. However, DMARD prescription still does not meet clinical recommendations, specifically in RF-negative patients. Since seronegative RA is a treatable disease, this group should not be overlooked.

Authors: G. Westhoff, M. Schneider, H. Raspe, H. Zeidler, C. Runge, T. Volmer, A. Zink

Date Published: 2009

Publication Type: Journal

Long-term outcome of patients with polymyositis/ dermatomyositis and anti-PM-Scl antibody

Abstract (Expand)

BACKGROUND: To date, no series has analysed long-term outcome in patients with polymyositis/dermatomyositis (PM/DM) with anti-PM-Scl antibody. OBJECTIVES: The aims of the present study were: (i) to … assess clinical features and long-term outcome, including organ complications, functional course and mortality rate, in patients with isolated PM/DM with anti-PM-Scl antibody; and (ii) to evaluate prevalence, characteristics and long-term outcome of interstitial lung disease (ILD) in patients with isolated PM/DM with anti-PM-Scl antibody. METHODS: The medical records of 20 consecutive patients with isolated PM/DM with anti-PM-Scl antibody were reviewed. RESULTS: Two patients (10%) achieved remission of PM/DM, whereas 14 (70%) improved and four (20%) had a worsened clinical status. Short-term recurrences (during tapering of therapy) occurred in nine patients and long-term recurrences (after discontinuation of therapy) in three patients. Moreover, patients with PM/DM with anti-PM-Scl antibody exhibited severe complications, as follows: oesophageal involvement (n = 4) requiring enteral feeding in three cases, ventilatory insufficiency (n = 3) requiring mechanical ventilation in two cases; three other patients had cancer. Interestingly, patients with PM/DM with anti-PM-Scl antibody often presented symptoms that are usually found in antisynthetase syndrome, i.e. hyperkeratotic rhagadiform hand symptoms (n = 2; 10%), Raynaud’s phenomenon (n = 8; 40%), arthralgia/arthritis (n = 7; 35%) and ILD (n = 12; 60%). In our cohort, the associated ILD often required combined therapy of steroids and immunosuppressive agents. CONCLUSIONS: Our series suggests that the presence of anti-PM-Scl antibody is not a good prognostic factor in patients with PM/DM, as there appears to be an association with lung and oesophageal involvement; in addition, anti-PM-Scl antibody may coexist with malignancy in patients with PM/DM. Furthermore, anti-PM-Scl antibody-positive patients with PM/DM often exhibit ’mechanic’s hands’, Raynaud’s phenomenon and joint involvement. Our latter findings raise the possibility that the immunogenetic background influences the autoantibody status of these patients; HLA-DR3 has, in fact, been found in association with antisynthetase syndrome antibodies and with anti-PM-Scl antibodies.

Authors: I. Marie, L. Lahaxe, O. Benveniste, K. Delavigne, D. Adoue, L. Mouthon, E. Hachulla, J. Constans, K. Tiev, E. Diot, H. Levesque, O. Boyer, F. Jouen

Date Published: 2010

Publication Type: Journal

[Epidemiology of primary Sjorgren’s syndrome]

Abstract (Expand)

According to the classification criteria of the American-European Consensus Group (AECG), the prevalence of primary Sjogren’s syndrome (pSS) of about 0.2% in the adult population and a yearly incidence … of 4/100.000 in the general population are far lower than previously assumed. Moreover, the repeatedly reported male/female ratio of 1:9 seems to lie more in the range of 1:20. Male pSS patients show fewer immunological, histopathological or sialographic findings and organ involvement. Information on age at disease onset has also changed over the last decade. Recent studies indicate an onset age of approximately 45 years as compared to 56 in earlier studies of the last decade. Patients with an early disease onset are more frequently positive for rheumatoid factor (RF) and/or anti-Ro/SS-A. These patients also seem to have a higher risk of developing hypocomplementemia or lymphadenopathy. As compared to earlier cohorts, the introduction of the rather specific AECG criteria will probably result in the participation of fewer men, younger patients in general and of more seriously ill patients in future cohorts. The change in the spectrum of pSS patients obviously reflects the altered classification criteria since the AECG criteria require anti-Ro/La positivity and therefore exclude a high number of patients with other immunological markers who also show severe sicca symptoms and organ involvements. About 5%-10% of pSS patients in rheumatological care suffer from severe extraglandular manifestations, which generally occur soon after disease onset. In particular, palpable purpura, hypocomplementemia, cryoglobulinemia and lymphoma are associated with increased mortality. In Germany, approximately one tenth of Sjogren syndrome patients receive specialized rheumatological care. There is still insufficient knowledge about the vast majority of pSS patients who are not treated by rheumatologists. These patients, as well as all those who, according to the AECG criteria, are not classified as having pSS either due to anti-Ro/La negativity or having secondary Sjogren’s syndrome, probably add up to at least 0.4% of the adult population which, at present, suffers from considerable immunopathologic sicca symptoms.

Authors: G. Westhoff, A. Zink

Date Published: 2010

Publication Type: Journal

Trends in treatment and outcomes of rheumatoid arthritis in Germany 1997-2007: results from the National Database of the German Collaborative Arthritis Centres

Abstract (Expand)

BACKGROUND: New strategies and options for the treatment of rheumatoid arthritis (RA) have evolved during the past decade. A study was undertaken to investigate to what extent this influenced daily … rheumatological care and how this translates into clinical and patient-reported outcomes. METHODS: Data from a total of 38 723 outpatients with RA enrolled in the National Database of the German Collaborative Arthritis Centres in the years 1997-2007 were analysed. The cross-sectional annual data were compared to detect time trends. RESULTS: Between 1997 and 2007 the prescription of combinations of traditional disease-modifying antirheumatic drugs (DMARDs) increased from 8% of all patients to 23%; biological agents were prescribed to 16% of patients with RA in 2007. The mean disease activity (DAS28) fell from 4.5 to 3.4 (median 4.5-3.2). The percentage of patients with low disease activity (DAS28 <3.2) increased significantly from 23% to 49%. The proportion of patients with >/=6 swollen joints fell from 43.1% in 1997 to 8.1% in 2007 and, in those with >/=6 tender joints, from 46.3% to 15.8%. There was a large decrease in the total annual number of days of sick leave due to the rheumatic condition from 27.2 to 8.8 days per gainfully employed person. This reduction is far beyond the decline in the general population. There was also a tendency to higher participation in the work force, specifically in older patients, reflecting the trend seen in the general population. CONCLUSIONS: The intensity of drug treatment in patients with RA has increased during the past 7 years. This has been accompanied by not only a decrease in disease activity but also a considerable reduction of economic losses due to sick leave and permanent work disability.

Authors: S. Ziegler, D. Huscher, K. Karberg, A. Krause, S. Wassenberg, A. Zink

Date Published: 2010

Publication Type: Journal

[How closely does rheumatology treatment follow the guidelines?: ambition and reality]

Abstract (Expand)

In 2005, the first evidence-based German guideline on the management of early rheumatoid arthritis (RA) was published. With data from the national database of the German Collaborative Arthritis Centres … and other health care studies we evaluated to what extent current health care is in accordance with the guideline’s recommendations.A total of 66% of all newly referred RA patients seen at the national database centers in 2008 achieved the goal of seeing a rheumatologist within 3 months of symptom onset, while 75% were seen within 6 months. Before referral, 25% of the patients had DMARD therapy and 19% glucocorticoids. Of the patients in rheumatological care, 90% received DMARDs. The availability of early arthritis clinics determines the promptness of access to a rheumatologist.After 6 years of rheumatological care, around 80% of patients continuously seen were still under treatment with a conventional or biological DMARD. The highest continuation rates were seen for methotrexate monotherapy. Biologic agents were given in 2008 to 20% of patients. Of those with "severe" or "very severe" disease, 42% received biologics and 21% DMARD combination therapy. Low-dose glucocorticoids are the standard of care; of patients in rheumatological care, 88% received dosages up to 7.5 mg/d and 74% of up to 5 mg/d.

Authors: A. Zink, D. Huscher, M. Schneider

Date Published: 2010

Publication Type: Journal

Finalisation and validation of the rheumatoid arthritis impact of disease score, a patient-derived composite measure of impact of rheumatoid arthritis: a EULAR initiative

Abstract (Expand)

OBJECTIVE: A patient-derived composite measure of the impact of rheumatoid arthritis (RA), the rheumatoid arthritis impact of disease (RAID) score, takes into account pain, functional capacity, fatigue, … physical and emotional wellbeing, quality of sleep and coping. The objectives were to finalise the RAID and examine its psychometric properties. METHODS: An international multicentre cross-sectional and longitudinal study of consecutive RA patients from 12 European countries was conducted to examine the psychometric properties of the different combinations of instruments that might be included within the RAID combinations scale (numeric rating scales (NRS) or various questionnaires). Construct validity was assessed cross-sectionally by Spearman correlation, reliability by intraclass correlation coefficient (ICC) in 50 stable patients, and sensitivity to change by standardised response means (SRM) in 88 patients whose treatment was intensified. RESULTS: 570 patients (79% women, mean +/- SD age 56 +/- 13 years, disease duration 12.5 +/- 10.3 years, disease activity score (DAS28) 4.1 +/- 1.6) participated in the validation study. NRS questions performed as well as longer combinations of questionnaires: the final RAID score is composed of seven NRS questions. The final RAID correlated strongly with patient global (R=0.76) and significantly also with other outcomes (DAS28 R=0.69, short form 36 physical -0.59 and mental -0.55, p<0.0001 for all). Reliability was high (ICC 0.90; 95% CI 0.84 to 0.94) and sensitivity to change was good (SRM 0.98 (0.96 to 1.00) compared with DAS28 SRM 1.06 (1.01 to 1.11)). CONCLUSION: The RAID score is a patient-derived composite score assessing the seven most important domains of impact of RA. This score is now validated; sensitivity to change should be further examined in larger studies.

Authors: L. Gossec, S. Paternotte, G. J. Aanerud, A. Balanescu, D. T. Boumpas, L. Carmona, M. de Wit, B. A. Dijkmans, M. Dougados, M. Englbrecht, F. Gogus, T. Heiberg, C. Hernandez, J. R. Kirwan, E. M. Mola, M. M. Cerinic, K. Otsa, G. Schett, M. Scholte-Voshaar, T. Sokka, G. von Krause, G. A. Wells, T. K. Kvien

Date Published: 2011

Publication Type: Journal

Patients with polymyositis or dermatomyositis have reduced grip force and health-related quality of life in comparison with reference values: an observational study

Abstract (Expand)

OBJECTIVES: The aims of this study were to investigate hand function in PM and DM patients and compare this with reference values in healthy individuals and also to investigate if hand function correlated … with activity performance and health-related quality of life. METHODS: An observational cross-sectional study was performed in 18 women and 13 men with PM or DM with established disease. Grip force and hand mobility were assessed by Grippit and Escola Paulista de Medicina-Range of Motion scale. Activity performance was measured with myositis activities profile and health-related quality of life by short form-36 (SF-36). RESULTS: Women and men with PM and DM with mean disease duration of 6.8 (5.5) years had a significantly lower grip force than gender- and age-matched healthy individuals (women 71% and men 60%). They also had significantly lower mean values in all dimensions of the health-related quality of life instrument SF-36 compared with the Swedish population. In patients with PM and DM, the grip force correlated significantly with the ability to perform domestic activities. In women with PM and DM, the grip force correlated significantly with the health-related quality of life dimensions vitality and mental health. There were no significant differences between patients with PM and DM regarding grip force, hand mobility, activity performance or health-related quality of life. CONCLUSIONS: Patients with PM or DM have reduced grip force that could influence activity performance and health-related quality of life.

Authors: M. Regardt, E. Welin Henriksson, H. Alexanderson, I. E. Lundberg

Date Published: 2011

Publication Type: Journal

Measures of adult and juvenile dermatomyositis, polymyositis, and inclusion body myositis: Physician and Patient/Parent Global Activity, Manual Muscle Testing (MMT), Health Assessment Questionnaire (HAQ)/Childhood Health Assessment Questionnaire (C-HAQ), Childhood Myositis Assessment Scale (CMAS), Myositis Disease Activity Assessment Tool (MDAAT), Disease Activity Score (DAS), Short Form 36 (SF-36), Child Health Questionnaire (CHQ), physician global damage, Myositis Damage Index (MDI), Quantitative Muscle Testing (QMT), Myositis Functional Index-2 (FI-2), Myositis Activities Profile (MAP), Inclusion Body Myositis Functional Rating Scale (IBMFRS), Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), Cutaneous Assessment Tool (CAT), Dermatomyositis Skin Severity Index (DSSI), Skindex, and Dermatology Life Quality Index (DLQI)

Abstract

Not specified

Authors: L. G. Rider, V. P. Werth, A. M. Huber, H. Alexanderson, A. P. Rao, N. Ruperto, L. Herbelin, R. Barohn, D. Isenberg, F. W. Miller

Date Published: 2011

Publication Type: Journal

Immunosuppressant and immunomodulatory treatment for dermatomyositis and polymyositis

Abstract (Expand)

BACKGROUND: Idiopathic inflammatory myopathies are chronic diseases with significant mortality and morbidity. Whilst immunosuppressive and immunomodulatory therapies are frequently used, the optimal … therapeutic regimen remains unclear. This is an update of a review first published in 2005. OBJECTIVES: To assess the effects of immunosuppressants and immunomodulatory treatments for dermatomyositis and polymyositis. SEARCH METHODS: We searched the Cochrane Neuromuscular Disease Group Specialized Register (August 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3 2011), MEDLINE (January 1966 to August 2011), EMBASE (January 1980 to August 2011) and clinicaltrials.gov (August 2011). We checked the bibliographies of identified trials and wrote to disease experts. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) or quasi-RCTs involving participants with probable or definite dermatomyositis and polymyositis as defined by the criteria of Bohan and Peter, or definite, probable or mild/early by the criteria of Dalakas. In participants without a classical rash of dermatomyositis, inclusion body myositis should have been excluded by muscle biopsy. We considered any immunosuppressant or immunomodulatory treatment. The two primary outcomes were the change in a function or disability scale measured as the proportion of participants improving one grade, two grades etc, predefined based on the scales used in the studies after at least six months, and a 15% or greater improvement in muscle strength compared with baseline after at least six months. Other outcomes were: the International Myositis Assessment and Clinical Studies Group (IMACS) definition of improvement, number of relapses and time to relapse, remission and time-to-remission, cumulative corticosteroid dose and serious adverse effects. DATA COLLECTION AND ANALYSIS: Two authors independently selected papers, extracted data and assessed risk of bias in included studies. They collected adverse event data from the included studies. MAIN RESULTS: The review authors identified fourteen 14 relevant RCTs. They excluded four trials.The 10 included studies, four of which have been added in this update, included a total of 258 participants. Six studies compared an immunosuppressant or immunomodulator with placebo control, and four studies compared two immunosuppressant regimes with each other. Most of the studies were small (the largest had 62 participants) and many of the reports contained insufficient information to assess risk of bias.Amongst the six studies comparing immunosuppressant with placebo, one study, investigating intravenous immunoglobulin (IVIg), showed statistically significant improvement in scores of muscle strength in the IVIg group over three months. Another study investigating etanercept showed some evidence of a steroid sparing effect, a secondary outcome in this review, but no improvement in other assessed outcomes. The other four randomised placebo-controlled trials assessed either plasma exchange and leukapheresis, eculizumab, infliximab or azathioprine against placebo and all produced negative results.Three of the four studies comparing two immunosuppressant regimes (azathioprine with methotrexate, ciclosporin with methotrexate, and intramuscular methotrexate with oral methotrexate plus azathioprine) showed no statistically significant difference in efficacy between the treatment regimes. The fourth study comparing pulsed oral dexamethasone with daily oral prednisolone and found that the dexamethasone regime had a shorter median time to relapse but fewer side effects.Immunosuppressants were associated with significant side effects. AUTHORS’ CONCLUSIONS: This systematic review highlights the lack of high quality RCTs that assess the efficacy and toxicity of immunosuppressants in inflammatory myositis.

Authors: P. A. Gordon, J. B. Winer, J. E. Hoogendijk, E. H. Choy

Date Published: 2012

Publication Type: Journal

Morbidity and mortality in adult polymyositis and dermatomyositis

Abstract (Expand)

Before the use of corticosteroids, the prognosis for polymyositis/dermatomyositis (PM/DM) was extremely poor. To date, although overall prognosis appears to be better, PM and DM are still considered … to be associated with increased morbidity, primarily related to severe muscle weakness and visceral involvement. Recent series underline that only 20% to 40% of treated patients will achieve PM/DM remission, whereas 60% to 80% will experience a polycyclic or chronic, continuous course of the disease. PM/DM further continues to have a great impact on life in medium- and long-term follow-up, as up to 80% of treated patients are still disabled (using Health Assessment Questionnaire scores). The overall mortality ratio in PM/DM patients also remains threefold higher compared with the general population, with cancer, lung, and cardiac complications and infections being the most common causes of deaths. Predictive factors for a poor prognosis in PM/DM patients are older age, involvement of lung and cardiac systems, dysphagia, cancer, and serum myositis-specific antibodies (including coexistent presence of anti-Ro52 and anti-Jo1 antibodies, anti-signal recognition particle antibody, anti-155/140, and anti-CADM-140 antibodies).

Author: I. Marie

Date Published: 2012

Publication Type: Journal

Predictors of survival in a cohort of patients with polymyositis and dermatomyositis: effect of corticosteroids, methotrexate and azathioprine

Abstract (Expand)

INTRODUCTION: The idiopathic inflammatory myopathies are rare diseases for which data regarding the natural history, response to therapies and factors affecting mortality are needed. We performed this … study to examine the effects of treatment and clinical features on survival in polymyositis and dermatomyositis patients. METHODS: A total of 160 consecutive patients (77 with polymyositis and 83 with dermatomyositis) seen at the University of Michigan from 1997 to 2003 were included. Medical records were abstracted for clinical, laboratory and therapeutic data, including initial steroid regimen and immunosuppressive use. State vital records were utilized to derive mortality and cause of death data. Survival was modeled by left-truncated Kaplan-Meier estimation and Cox regression. RESULTS: The 5- and 10-year survival estimates were 77% (95% CI = 66 to 85), and 62% (95% CI = 48 to 73), respectively, and the rates were similar for polymyositis and dermatomyositis. Survival between the sexes was similar through 5 years and significantly lower thereafter for males (10-year survival: 18% male, 73% female; P = 0.002 for 5- to 10-year interval). The sex disparity was restricted to the polymyositis group. Increased age at diagnosis and non-Caucasian race were associated with lower survival. Intravenous versus oral corticosteroid use was associated with a higher risk of death among Caucasians (HR = 10.6, 95% CI = 2.1 to 52.8). Early survival between patients treated with methotrexate versus azathioprine was similar, but survival at 10 years was higher for the methotrexate-treated group (76% vs 52%, P = 0.046 for 5- to 10-year interval). CONCLUSIONS: Patients treated initially with intravenous corticosteroids had higher mortality, which was likely related to disease severity. Both methotrexate and azathioprine showed similar early survival benefits as first-line immunosuppressive drugs. Survival was higher between 5 and 10 years in the methotrexate-treated group, but could not be confirmed in multivariable modeling for the full follow-up period. Other important predictors of long-term survival included younger age, female sex and Caucasian race.

Authors: E. Schiopu, K. Phillips, P. M. MacDonald, L. J. Crofford, E. C. Somers

Date Published: 2012

Publication Type: Journal

Clinical presentation, burden of disease and treatment in young-onset and late-onset rheumatoid arthritis: a matched-pairs analysis taking age and disease duration into account

Abstract (Expand)

OBJECTIVES: The aim of this study is to compare clinical features and treatment of young onset rheumatoid arthritis with late-onset rheumatoid arthritis. METHODS: Nine thousand five hundred forty-one … patients with rheumatoid arthritis (RA) enrolled in the national database of the German Collaborative Arthritis Centres in 2007-2009 were stratified by age at disease onset: up to 65 years (YORA), >65 years (LORA). To enable unbiased comparisons between the two groups despite their systematic differences in age and disease duration, we performed two separate matched-pairs analyses: the impact of current age was assessed by matching YORA and LORA patients for disease duration and sex (n=1,550 pairs). To identify the influence of disease duration, a second sample matched for age and sex (n=1,158 pairs) was drawn. RESULTS: At identical age, YORA patients had higher disease activity (DAS28), worse functional capacity and were less frequently in remission when compared with LORA patients. YORA patients also suffered more frequently from RA-related co-morbidities such as cardiovascular disease, chronic renal disease and osteoporosis. Matched for disease duration, there were no differences between the two groups concerning disease severity and remission rates, global health or pain intensity. Independent of age or disease duration, YORA patients reported more sleep disorders and fatigue. LORA patients received significantly fewer synthetic or biologic DMARDs than YORA patients. CONCLUSIONS: Duration of RA, rather than age, explains differences in disease burden between YORA and LORA patients. The lower prescription rates of synthetic and in particular biologic DMARDs, despite lower remission rates, indicate a potential treatment deficit in older patients.

Authors: D. Huscher, C. Sengler, E. Gromnica-Ihle, S. Bischoff, T. Eidner, W. Ochs, J. Richter, A. Zink

Date Published: 2013

Publication Type: Journal

Measurement properties of the EQ-5D-5L compared to the EQ-5D-3L across eight patient groups: a multi-country study

Abstract (Expand)

PURPOSE: The aim of this study was to assess the measurement properties of the 5-level classification system of the EQ-5D (5L), in comparison with the 3-level EQ-5D (3L). METHODS: Participants (n = … 3,919) from six countries, including eight patient groups with chronic conditions (cardiovascular disease, respiratory disease, depression, diabetes, liver disease, personality disorders, arthritis, and stroke) and a student cohort, completed the 3L and 5L and, for most participants, also dimension-specific rating scales. The 3L and 5L were compared in terms of feasibility (missing values), redistribution properties, ceiling, discriminatory power, convergent validity, and known-groups validity. RESULTS: Missing values were on average 0.8% for 5L and 1.3% for 3L. In total, 2.9% of responses were inconsistent between 5L and 3L. Redistribution from 3L to 5L using EQ dimension-specific rating scales as reference was validated for all 35 3L-5L-level combinations. For 5L, 683 unique health states were observed versus 124 for 3L. The ceiling was reduced from 20.2% (3L) to 16.0% (5L). Absolute discriminatory power (Shannon index) improved considerably with 5L (mean 1.87 for 5L versus 1.24 for 3L), and relative discriminatory power (Shannon Evenness index) improved slightly (mean 0.81 for 5L versus 0.78 for 3L). Convergent validity with WHO-5 was demonstrated and improved slightly with 5L. Known-groups validity was confirmed for both 5L and 3L. CONCLUSIONS: The EQ-5D-5L appears to be a valid extension of the 3-level system which improves upon the measurement properties, reducing the ceiling while improving discriminatory power and establishing convergent and known-groups validity.

Authors: M. F. Janssen, A. S. Pickard, D. Golicki, C. Gudex, M. Niewada, L. Scalone, P. Swinburn, J. Busschbach

Date Published: 2013

Publication Type: Journal

Performance of the 2011 ACR/EULAR preliminary remission criteria compared with DAS28 remission in unselected patients with rheumatoid arthritis

Abstract (Expand)

OBJECTIVE: To compare the performance of the preliminary American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) remission criteria with the 28-joint count Disease Activity Score … (DAS28) remission in unselected ’real-life’ patients. METHODS: Remission was calculated according to the DAS28 and to both versions of the ACR/EULAR criteria (Boolean or Simplified Disease Activity Index (SDAI)-based) for 6864 patients with rheumatoid arthritis (RA) who were enrolled in the national database of the German Collaborative Arthritis Centres between 2007 and 2009. Logistic regression analyses identified factors that were responsible for patients in DAS28 remission to miss the new criteria. In addition, the functional status of patients who fulfilled the different remission criteria was compared with that of an age- and sex-matched population sample. RESULTS: Of all patients, 28% were in DAS28, 7% in Boolean and 11% in SDAI remission. Of those in DAS28 remission, 21.0% were also in Boolean and 34% also in SDAI remission. Higher scores for pain and fatigue, the presence of degenerative spine disease, longer disease duration and male gender were significantly associated with missing the new criteria despite being in DAS28 remission. Compared with age- and sex-matched samples from the general population, patients in DAS28 remission had a similar functional ability while patients in remission according to the new criteria had better functional scores. CONCLUSIONS: Patients fulfilling the new remission criteria tend to be not only free from active RA, but also from other disabling diseases. If these criteria are applied in clinical practice to guide treatment decisions, the impact of comorbidity should be taken into account.

Authors: K. Thiele, D. Huscher, S. Bischoff, S. Spathling-Mestekemper, M. Backhaus, M. Aringer, T. Kohlmann, A. Zink, Centres German Collaborative Arthritis

Date Published: 2013

Publication Type: Journal

[Gender-specific differences in comorbidities of rheumatoid arthritis]

Abstract (Expand)

BACKGROUND: Comorbidities play an important role in the course and therapy of rheumatoid arthritis (RA). Sex-specific aspects are observed with regard to prevalence and manifestation of RA-related … comorbidities. AIM: A summary of current insights into sex and gender-related aspects of frequent comorbidities in RA is given. MATERIAL AND METHODS: National data were analyzed and literature findings from meta-analyses, observational studies and reviews with regard to gender and RA-associated comorbidities are presented. RESULTS: There are gender-specific differences in the prevalence of comorbidities of RA. Depression, fibromyalgia and hypothyroidism are more frequent in women than in men, whereas cardiovascular diseases and diabetes are more common in men. Osteoarthritis and osteoporosis are frequent in both sexes. CONCLUSION: Sex and gender-specific aspects should be taken into consideration in the diagnostics and treatment of RA-related comorbidities.

Author: K. Albrecht

Date Published: 2014

Publication Type: Journal

Changes in referral, treatment and outcomes in patients with systemic lupus erythematosus in Germany in the 1990s and the 2000s

Abstract (Expand)

OBJECTIVE: To evaluate trends in the referral, treatment and outcome of patients with systemic lupus erythematosus (SLE) in Germany over two decades. METHODS: From 1993 to 2012, approximately 1200 … patients with SLE were recorded annually in the national database of the German Collaborative Arthritis Centres. Treatment patterns, healthcare use and outcomes, such as disease activity, function and work participation, were evaluated over time. Furthermore, two distinct cohorts of patients (enrolment 1994-1998, n=467; and 2004-2008, n=376) observed over 5 years were assessed for changes in outcomes. RESULTS: The mean disease duration at the first visit to a rheumatologist decreased from 2.6 (1994) to 1.5 (2012) years. Glucocorticoids (69%), antimalarials (56%), azathioprine (22%), non-steroidal anti-inflammatory drugs (23%) and mycophenolate mofetil (15%) were the most frequently used treatments in 2012. A significant increase was observed in the use of antimalarials and mycophenolate mofetil. The use of glucocorticoids at >7.5 mg/day decreased from 27% (1994) to 10% (2012). The average length of sick leave taken due to SLE declined from 9 weeks (1997) to 6 weeks (2012). When comparing the two longitudinal cohorts, in the cohort from the 2000s, the intraindividual decline of disease activity was significantly stronger (p<0.001), and fewer patients retired early (36% vs 46%). CONCLUSIONS: The disease activity and resource use declined considerably over the observation period, and more patients remained in the labour force. Earlier treatment onset, faster modification of the treatment regimen and more intensive use of anti-inflammatory therapy may account for the improved outcomes in patients with SLE across the years.

Authors: K. Albrecht, D. Huscher, J. Richter, M. Backhaus, S. Bischoff, I. Kotter, K. Thiele, A. Zink

Date Published: 2014

Publication Type: Journal

Patient-reported outcomes and adult patients’ disease experience in the idiopathic inflammatory myopathies. report from the OMERACT 11 Myositis Special Interest Group

Abstract (Expand)

The newly formed Outcome Measures in Rheumatology (OMERACT) Myositis Special Interest Group (SIG) was established to examine patient-reported outcome measures (PROM) in myositis. At OMERACT 11, a … literature review of PROM used in the idiopathic inflammatory myopathies (IIM) and other neuromuscular conditions was presented. The group examined in more detail 2 PROM more extensively evaluated in patients with IIM, the Myositis Activities Profile, and the McMaster-Toronto Arthritis Patient Preference Disability Questionnaire, through the OMERACT filter of truth, discrimination, and feasibility. Preliminary results from a qualitative study of patients with myositis regarding their symptoms were discussed that emphasized the range of symptoms experienced: pain, physical tightness/stiffness, fatigue, disease effect on emotional life and relationships, and treatment-related side effects. Following discussion of these results and following additional discussions since OMERACT 11, a research agenda was developed. The next step in evaluating PROM in IIM will require additional focus groups with a spectrum of patients with different myositis disease phenotypes and manifestations across a range of disease activity, and from multiple international settings. The group will initially focus on dermatomyositis and polymyositis in adults. Qualitative analysis will facilitate the identification of commonalities and divergent patient-relevant aspects of disease, insights that are critical given the heterogeneous manifestations of these diseases. Based on these qualitative studies, existing myositis PROM can be examined to more thoroughly assess content validity, and will be important to identify gaps in domain measurement that will be required to develop a preliminary core set of patient-relevant domains for IIM.

Authors: H. Alexanderson, M. Del Grande, C. O. Bingham, A. M. Orbai, C. Sarver, K. Clegg-Smith, I. E. Lundberg, Y. W. Song, L. Christopher-Stine

Date Published: 2014

Publication Type: Journal

Diagnosis, pathogenesis and treatment of myositis: recent advances

Abstract (Expand)

Dermatomyositis (DM), polymyositis (PM), necrotizing myopathy (NM) and inclusion body myositis (IBM) are four distinct subtypes of idiopathic inflammatory myopathies - in short myositis. Recent studies … have shed some light on the unique pathogenesis of each entity. Some of the clinical features are distinct, but muscle biopsy is indispensable for making a reliable diagnosis. The use of magnetic resonance imaging of skeletal muscles and detection of myositis-specific autoantibodies have become useful additions to our diagnostic repertoire. Only few controlled trials are available to substantiate current treatment approaches for myositis and hopes are high that novel modalities will become available within the next few years. In this review we provide an up-to-date overview of the pathogenesis and diagnostic approach of myositis. We aim to present a guide towards therapeutic and general management.

Authors: P. O. Carstens, J. Schmidt

Date Published: 2014

Publication Type: Journal

[Trends in rehabilitation of patients with rheumatic diseases in Germany]

Abstract (Expand)

Recent Deutsche Gesellschaft fur Rheumatologie (DGRh, German Society of Rheumatology) guidelines emphasized the significance of coordinated multidisciplinary care and rehabilitation of patients with … inflammatory rheumatic diseases. Nationwide data from the German pension insurance funds showed that inpatient rehabilitation due to rheumatoid arthritis (RA) varied by a factor of 2.6 between the different German states. From 2000 to 2012 rehabilitation measures were reduced by one third, most significantly in men with ankylosing spondylitis (AS). Rehabilitation measures because of RA or AS were provided up to 14 times more frequently by the German statutory pension insurance scheme compared with a large compulsory health insurance which is responsible for rehabilitation measures after retirement. In rehabilitation centers with high numbers of patients with inflammatory rheumatic diseases, higher structural and process quality were demonstrated. In 2011 a total of 40 % of RA patients in the national database of the collaborative arthritis centers showed medium or severe functional limitations. Among these disabled RA patients inpatient rehabilitation was reduced by about 50 % between 1995 and 2011. Out of all RA patients from outpatient rheumatology care with severe functional limitations 38 % had no functional restoration therapy within the previous 12 months with a high variation between rheumatologists. Experiences from other European countries may inspire German rheumatologists and other involved health professionals to initiate a wider range of rehabilitative interventions in the future.

Authors: W. Mau, W. Beyer, I. Ehlebracht-Konig, J. M. Engel, E. Genth, W. H. Jackel, U. Lange, K. Thiele

Date Published: 2014

Publication Type: Journal

[Trends of work force participation of patients with rheumatic diseases : results from German social insurance data and the national database of the German collaborative arthritis centers]

Abstract (Expand)

Positive therapeutic effects on the work force participation derived from international clinical trials may not be directly transferable to the community based care in Germany. Therefore recent changes … of data regarding sick leave (SL), work disability pension (WDP) and employment from the social insurance and from the national database of the German collaborative arthritis centers were analyzed covering a time period of at least 10 years. Health insurance data showed a steeper decline in the average duration of SL caused by rheumatoid arthritis (RA), ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) compared with all other diseases. In RA patients from the collaborative arthritis centers the mean duration of SL was much more reduced than the average duration of SL for members of the compulsory health insurance. The proportion of gainfully employed RA patients in collaborative arthritis centers has particularly increased in women. According to data from the pension insurance fund less incident cases of WDP due to RA, AS, and SLE have been observed than WDP caused by all other diseases. Thus different nationwide data show positive changes of the work force participation of individuals suffering from inflammatory rheumatic diseases in Germany.

Authors: W. Mau, K. Thiele, J. Lamprecht

Date Published: 2014

Publication Type: Journal

The epidemiology of Sjogren’s syndrome

Abstract (Expand)

Sjogren’s syndrome is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands. It can present as an entity by itself, primary Sjogren’s syndrome (pSS), or in … addition to another autoimmune disease, secondary Sjogren’s syndrome (sSS). pSS has a strong female propensity and is more prevalent in Caucasian women, with the mean age of onset usually in the 4th to 5th decade. Clinical presentation varies from mild symptoms, such as classic sicca symptoms of dry eyes and dry mouth, keratoconjunctivitis sicca, and xerostomia, to severe systemic symptoms, involving multiple organ systems. Furthermore, a range of autoantibodies can be present in Sjogren’s syndrome (anti-SSA/Ro and anti-SSB/La antibodies, rheumatoid factor, cryoglobulins, antinuclear antibodies), complicating the presentation. The heterogeneity of signs and symptoms has led to the development of multiple classification criteria. However, there is no accepted universal classification criterion for the diagnosis of Sjogren’s syndrome. There are a limited number of studies that have been published on the epidemiology of Sjogren’s syndrome, and the incidence and prevalence of the disease varies according to the classification criteria used. The data is further confounded by selection bias and misclassification bias, making it difficult for interpretation. The aim of this review is to understand the reported incidence and prevalence on pSS and sSS, the frequency of autoantibodies, and the risk of malignancy, which has been associated with pSS, taking into account the different classification criteria used.

Authors: R. Patel, A. Shahane

Date Published: 2014

Publication Type: Journal

[Healthcare research in rheumatology. Current state]

Abstract (Expand)

Health services research in rheumatology investigates the healthcare needs, the quality of care and trends in healthcare for patients with musculoskeletal disorders. Using rheumatoid arthritis (RA) as … an example, key results of health services research during the last 25 years are summarized. There are currently approximately 540,000 persons with RA in Germany of which some two thirds are regularly seen by rheumatologists. The data from the national database of the German collaborative arthritis centres show that patients are now seen earlier and to a greater extent. The intensity of drug treatment with synthetic or biological disease-modifying antirheumatic drugs (DMARDs) has increased continuously. At the same time, the mean disease activity (DAS28) has decreased from 4.7 to 3.3 and approximately 50 % of patients treated early achieve remission. Physician-rated disease severity has considerably improved and fewer patients suffer from erosive disease. This corresponds with improvements in functional capacity and work participation. Health services research impressively shows the advances in rheumatological care. Further improvements at the population level are limited by the low numbers of rheumatologists in outpatient care.

Author: A. Zink

Date Published: 2014

Publication Type: Journal

Is primary Sjogren’s syndrome an orphan disease? A critical appraisal of prevalence studies in Europe

Abstract

Not specified

Authors: D. Cornec, L. Chiche

Date Published: 2015

Publication Type: Journal

The Differential Diagnosis of Dry Eyes, Dry Mouth, and Parotidomegaly: A Comprehensive Review

Abstract (Expand)

Primary Sjogren’s syndrome (pSS) is a frequent autoimmune systemic disease, clinically characterized by eyes and mouth dryness in all patients, salivary gland swelling or extraglandular systemic … manifestations in half of the patients, and development of lymphoma in 5 to 10 % of the patients. However, patients presenting with sicca symptoms or salivary gland swelling may have a variety of conditions that may require very different investigations, treatments, or follow-up. Eye and/or mouth dryness is a frequent complaint in clinical setting, and its frequency increases with age. When evaluating a patient with suspected pSS, the first step is to rule out its differential diagnoses, before looking for positive arguments for the disease. Knowledge of normal and abnormal lachrymal and salivary gland physiology allows the clinician to prescribe the most adapted procedures for evaluating their function and structure. New tests have been developed in recent years for evaluating these patients, notably new ocular surface staining scores or salivary gland ultrasonography. We describe the different diagnoses performed in our monocentric cohort of 240 patients with suspected pSS. The most frequent diagnoses are pSS, other systemic autoimmune diseases, idiopathic sicca syndrome and drug-induced sicca syndrome. However, other diseases are important to rule out due to their specific management, such as sarcoidosis, granulomatosis with polyangeitis, IgG4-related disease, chronic hepatitis C virus or human immunodeficiency virus infections, graft-versus-host disease, and head and neck radiation therapy. At the light of these data, we propose a core of minimal investigations to be performed when evaluating a patient with suspected pSS.

Authors: D. Cornec, A. Saraux, S. Jousse-Joulin, J. O. Pers, S. Boisrame-Gastrin, Y. Renaudineau, Y. Gauvin, A. M. Roguedas-Contios, S. Genestet, M. Chastaing, B. Cochener, V. Devauchelle-Pensec

Date Published: 2015

Publication Type: Journal

Evolution of cost structures in rheumatoid arthritis over the past decade

Abstract (Expand)

OBJECTIVE: To estimate the changes in direct and indirect costs induced by patients with rheumatoid arthritis (RA) in German rheumatology, between 2002 and 2011. To examine the impact of functional … status on various cost domains. To compare the direct costs incurred by patients at working age (18-64 years) to patients at an age of retirement (>/=65 years). METHODS: We analysed data from the National Database of the German Collaborative Arthritis Centres with about 3400 patients each year. Costs were calculated using fixed prices as well as annually updated cost factors. Indirect costs were calculated using the human capital as well as the friction cost approaches. RESULTS: There was a considerable increase in direct costs: from euro4914 to euro8206 in patients aged 18-64, and from euro4100 to euro6221 in those aged >/=65, attributable to increasing prescription of biologic agents (18-64 years from 5.6% to 31.2%, >/=65 years from 2.8% to 19.2%). This was accompanied by decreasing inpatient treatment expenses and indirect costs due to sick leave and work disability. The total growth of cost, on average, was euro2437-2981 for patients at working age, and euro2121 for patients at retirement age. CONCLUSIONS: The increase in treatment costs for RA over the last decade was associated with lower hospitalisation rates, better functional status and a lower incidence of work disability, offsetting a large proportion of risen drug costs. Since the rise in drug costs has manifested a plateau from 2009 onwards, no relevant further increase in total costs for patients with RA treated in German rheumatology is expected.

Authors: D. Huscher, T. Mittendorf, U. von Hinuber, I. Kotter, G. Hoese, A. Pfafflin, S. Bischoff, A. Zink, Centres German Collaborative Arthritis

Date Published: 2015

Publication Type: Journal

Trends in treatment and outcomes of ankylosing spondylitis in outpatient rheumatological care in Germany between 2000 and 2012

Abstract (Expand)

OBJECTIVES: To describe changes in drug treatment and clinical outcomes of ankylosing spondylitis (AS) during the past decade. METHODS: The national database of the German collaborative arthritis centres … collects clinical and patient-derived data from unselected outpatients with inflammatory rheumatic diseases. Cross-sectional data from 2000 to 2012 of around 1000 patients with AS per year were compared with regard to clinical presentation and quality of life indicators. RESULTS: Non-steroidal anti-inflammatory drugs (NSAIDs) have been the predominant treatment choice in AS over the years with a prescription rate of 67% of patients in 2012. Currently, almost half of the patients with AS in German rheumatology centres are treated with tumour necrosis factor inhibitors (TNFi). Often, both treatments are used in combination (33%), followed by combinations of NSAIDs and synthetic disease modifying antirheumatic drugs (sDMARDs) with 23% or TNFi alone (21%). In 2012, 10% of patients each received NSAID or sDMARD monotherapy. Methotrexate, sulfasalazine, glucocorticoids and analgaesics alone or in combination with other treatments were given to 10% of patients, respectively. Over the years, we have seen remarkable improvements in disease control and patient reported outcomes. These developments are consistent with enhanced functional status, increasing employment rates and decreasing sick leave, hospitalisation and work disability. CONCLUSIONS: In the German rheumatology secondary/tertiary care setting, routine care of patients with AS has changed tremendously during the past decade. Increasingly, more efficacious treatment options are reflected in improved clinical outcomes, quality of life and participation in the labour force.

Authors: D. Huscher, K. Thiele, M. Rudwaleit, K. C. Albrecht, S. Bischoff, A. Krause, K. Karberg, S. Wassenberg, A. Zink

Date Published: 2015

Publication Type: Journal

Epidemiology of primary Sjogren’s syndrome: a systematic review and meta-analysis

Abstract (Expand)

OBJECTIVE: Epidemiological studies of primary Sjogren’s syndrome (pSS) are crucial for describing the burden to society and the public medical system and for shedding light on aetiology. Previous reports … of the epidemiology of pSS show variable outcomes. We conducted a systematic review of the epidemiology of pSS to assess the prevalence rates (PRs) and incidence rates (IRs), and to investigate possible geographic variations in pSS. METHODS: A systematic literature search of PubMed and Embase (updated to 22 October 2013) was performed to identify all published reports on the epidemiology of pSS. The incidence and prevalence rates of pSS were summarised with IRs or PRs and 95% CIs. RESULTS: The literature search yielded 1880 related citations. Only 21 fulfilled the inclusion criteria. According to a random-effects model, the pooled IR for pSS was 6.92 (95% CI 4.98 to 8.86) per 100 000 person-years. The overall PR was 60.82 (95% CI 43.69 to 77.94) cases per 100 000 inhabitants with a slightly lower estimate of Baodong Qin is BDQ, Jiaqi Wang is JQW, Zaixing Yang is ZXY, Renqian Zhong is RQZ. 43.03 (25.74 to 60.31) cases per 100 000 inhabitants when only considering population-based studies. The female/male ratio in incidence data was 9.15 (95% CI 3.35 to 13.18). The female/male ratio in prevalence data was 10.72 (95% CI 7.35 to 15.62). The overall age of pSS patients was 56.16 years (95% CI 52.54 to 59.78). CONCLUSIONS: Incidence and prevalence rates of pSS vary widely around the world. The results help us better understand the global epidemiology of pSS. Large population-based studies combining meticulous case-finding and case-ascertainment strategies are needed.

Authors: B. Qin, J. Wang, Z. Yang, M. Yang, N. Ma, F. Huang, R. Zhong

Date Published: 2015

Publication Type: Journal

Patients’ Experience of Myositis and Further Validation of a Myositis-specific Patient Reported Outcome Measure - Establishing Core Domains and Expanding Patient Input on Clinical Assessment in Myositis. Report from OMERACT 12

Abstract (Expand)

OBJECTIVE: The Outcome Measures in Rheumatology (OMERACT) myositis working group was established to examine patient-reported outcomes (PRO) as well as to validate patient-reported outcome measures … (PROM) in myositis. METHODS: Qualitative studies using focus group interviews and cognitive debriefing of the myositis-specific Myositis Activities Profile (MAP) were used to explore the experience of adults living with polymyositis (PM) and dermatomyositis (DM). RESULTS: Preliminary results underscore the importance of patient input in the development of PROM to ensure content validity. Results from multicenter focus groups indicate the range of symptoms experienced including pain, fatigue, and impaired cognitive function, which are not currently assessed in myositis. Preliminary cognitive debriefing of the MAP indicated that while content was deemed relevant and important, several activities were not included; and that questionnaire construction and wording may benefit from revision. A research agenda was developed to continue work toward optimizing PRO assessment in myositis with 2 work streams. The first would continue to conduct and analyze focus groups until saturation in the thematic analysis was achieved to develop a framework that encompassed the patient-relevant aspects of myositis. The second would continue cognitive debriefing of the MAP to identify potential areas for revision. There was agreement that further work would be needed for inclusion body myositis and juvenile dermatomyositis, and that the inclusion of additional contributors such as caregivers and individuals from the pharmaceutical/regulatory spheres would be desirable. CONCLUSIONS: The currently used PROM do not assess symptoms or the effects of disease that are most important to patients; this emphasizes the necessity of patient involvement. Our work provides concrete examples for PRO identification.

Authors: M. Regardt, P. Basharat, L. Christopher-Stine, C. Sarver, A. Bjorn, I. E. Lundberg, Y. Wook Song, C. O. Bingham, H. Alexanderson

Date Published: 2015

Publication Type: Journal

[Clinical remission in rheumatoid arthritis. Data from the early arthritis cohort study CAPEA]

Abstract (Expand)

OBJECTIVE: To evaluate remission rates and therapeutic strategies in the routine care of early rheumatoid arthritis. METHODS: Between 2010 and 2013, a total of 1,301 patients with early arthritis were … followed by 89 rheumatologists for up to 2 years in an early arthritis cohort (CAPEA). Complete 2-year data are available for 669 patients with rheumatoid arthritis. RESULTS: Ninety-three percent of patients were diagnosed with a moderate or high disease activity score (DAS28 > 3.2). Within 6 months, 40 % were in clinical remission (DAS28 < 2.6) and 21 % reached a low disease activity score (DAS28 > 2.6 to < 3.2). This proportion did not substantially increase during the 2-year follow-up. Methotrexate was the standard first-line treatment in 82 % of patients. During follow-up, 10 % were treated with a combination of disease-modifying antirheumatic drugs (DMARDs) and 12 % with biological agents. In 60 % of the patients who did not reach remission within 3 months (and 54 % of patients without remission by 6 months), treatment was not changed. At the beginning, 77 % of patients were treated with glucocorticoids at different starting doses (26 % < 7.5 mg, 29 % 7.5-20 mg, and 45 % >/= 20 mg of prednisolone per day). After 2 years, 47 % remained on glucocorticoids. CONCLUSION: While 40 % of patients achieved clinical remission through standard care within 6 months, disease activity remained moderate to high in 37 % of patients at 2 years. In these patients a more consistent application of treatment may have increased the response rates.

Authors: K. Albrecht, J. Callhoff, E. Edelmann, G. Schett, M. Schneider, A. Zink

Date Published: 2016

Publication Type: Journal

Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three large German rheumatoid arthritis databases

Abstract (Expand)

BACKGROUND: METARTHROS (Metabolic impact on joint and bone disease) is a nationwide German network to investigate the overlap between inflammatory and metabolic diseases. The objective of this study … was to compare the body mass index (BMI) distribution in patients with early and established rheumatoid arthritis (RA) with data from the general population, and to evaluate the association of BMI with patient characteristics and clinical markers. METHODS: The BMI distribution was examined with data collected at inclusion of patients in the early arthritis cohort CAPEA, the biologics register RABBIT, and the National database of the German Collaborative Arthritis Centers. A data source with a representative sample of the German population (German Ageing Survey) was used as a comparator. BMI categories of <18.5 kg/m(2) (underweight), 18.5 to <25 kg/m(2) (normal weight), 25 to <30 kg/m(2) (overweight), and >/=30 kg/m(2) (obese) were used. Patients were stratified by age and sex, and compared to controls from the German Ageing Survey. Associations between BMI and markers of disease activity were analysed with non-parametric tests and linear models. RESULTS: Data from 1207 (CAPEA), 12,230 (RABBIT), and 3424 (National database) RA patients and 6202 population controls were evaluated. The mean age was 56, 56, 62, and 62 years, respectively, the mean disease duration was 13 weeks, 9.9 years, and 13.5 years, respectively, and the mean disease activity score (DAS28) was 5.1, 5.2, and 3.1, respectively. In all RA cohorts, obesity was more frequent (23.8 %, 23.4 %, 21.4 %, respectively) than in controls (18.2 %). This applied to all age groups <70 years, was independent of disease duration, and was more pronounced in females. In all cohorts, the age at RA onset was associated with BMI, being higher in overweight/obese patients compared to normal-weight patients. Current smoking was negatively associated with BMI. Linear analyses revealed increased erythrocyte sedimentation rate (ESR) values in underweight and obese females, and an increasing disparity between tender joint counts (TJCs) and swollen joint counts (SJCs) in higher BMI categories. CONCLUSIONS: Compared to the general population, a higher prevalence of obesity was observed in all RA cohorts. The dominance of obesity in females and the different behaviour of disease activity markers in relation to the BMI in females indicate that additional parameters need to be considered when analysing the impact of obesity on inflammation in RA.

Authors: K. Albrecht, A. Richter, J. Callhoff, D. Huscher, G. Schett, A. Strangfeld, A. Zink

Date Published: 2016

Publication Type: Journal

Health-Related Quality of Life (HRQoL) in Idiopathic Inflammatory Myopathy: A Systematic Review

Abstract (Expand)

Health-related quality of life (HRQoL) is a research priority in chronic diseases. We undertook a systematic review (registration #CRD42015024939) to identify, appraise and synthesize the evidence … relating to HRQoL in idiopathic inflammatory myopathies (IIM). A comprehensive search was conducted in August 2015 using CINAHL, EMBase and Pubmed to identify studies reporting original data on HRQoL in IIM using generic HRQoL instruments. Characteristics of samples and results from selected studies were extracted and appraised using a standardized approach. Qualitative synthesis of the results was performed. Ten studies including a total of 654 IIM subjects were included in this systematic review. HRQoL was significantly impaired in all subsets of IIM compared with the general population. Disease activity, disease damage and chronic disease course were associated with poorer HRQoL. Insufficient or conflicting results were found in associations between clinical features, treatment, disease duration and mood or illness perception, and HRQoL in IIM. This study suggests that HRQoL is impaired in IIM. However, due to the paucity and heterogeneity of the evidence to date, robust estimates are lacking and significant knowledge gaps persist. There is a need for studies that systematically investigate the correlates and trajectory of HRQoL in IIM.

Authors: V. Leclair, M. Regardt, S. Wojcik, M. Hudson, Study Canadian Inflammatory Myopathy

Date Published: 2016

Publication Type: Journal

[Medical treatment of rheumatoid arthritis in 2014 : Current data from the German Collaborative Arthritis Centers]

Abstract (Expand)

BACKGROUND: Since the introduction of biologic treatment in rheumatoid arthritis (RA), disease activity and treatment modalities have changed substantially. The current provision and developments in … recent years are analyzed with annual data from the National Database of the Collaborative Arthritis Centers in Germany. METHODS: To analyze disease activity, diagnostics and treatment in RA patients in 2014 with regard to seropositivity and disease duration. Time trends from 2007-2014 are reported for disease activity (DAS28) distribution and biologic treatment. RESULTS: In 2014, a total of 8,084 RA patients were analyzed: 72 % were rheumatoid factor and/or ACPA positive, the mean age was 62 years and the mean disease duration 12 years. According to DAS28, 35.9 % were in remission, 19.2 % had low, 37.1 % moderate and 7.8 % high disease activity. An increase since 2007 was only observed in patients with a disease duration >2 years. Synthetic DMARDS were used for treatment in 78 %. Biologic treatment increased from 16 % (2007) to 27 % (2014). Especially those patients with a disease duration >5 years were treated more frequently with biologics. Seronegative patients had slightly less severe mean disease activity parameters. They were treated equally frequent with DMARDS but only half as often with biologics compared to seropositive patients. CONCLUSION: The use of biologics in RA patients has increased since 2007; however this was not observed in patients with short disease duration. Early intensive treatment adaption seems justified to improve disease activity in the large portion of patients who do not reach low disease activity under conventional DMARDs.

Authors: K. Albrecht, D. Huscher, T. Eidner, S. Kleinert, S. Spathling-Mestekemper, S. Bischoff, A. Zink

Date Published: 2017

Publication Type: Journal

[How frequent are poor prognostic markers in rheumatoid arthritis? : An estimate based on three epidemiologic cohorts]

Abstract (Expand)

BACKGROUND: Unfavorable prognostic factors-high disease activity, early erosions, and autoantibodies-should be considered when making treatment decisions in rheumatoid arthritis (RA). There are little … data on the frequency of individual poor prognostic factors among RA patients in daily care. METHODS: Disease activity (Disease Activity Score, DAS28), erosions, antibodies against citrullinated peptides or rheumatoid factor (ACPA/RF+), previous treatment failure, inflammation markers, and functional disability (FFbH < 70) were defined as prognostic factors. Different treatment decision making situations were evaluated in disease-modifying antirheumatic drug (DMARD)-naive patients from the early RA CAPEA cohort (n = 1059), and in patients from the biologics register RABBIT after failure of one (n = 2217) or more (n = 3280) conventional synthetic (cs)DMARDs or one (n = 1134) or more (n = 795) biologic (b)DMARDs. With the national database of German arthritis centers (NDB), the frequency of these factors was analyzed according to treatment strata (no/1(st)/2(nd)/3(rd) DMARD; n = 5707). RESULTS: In DMARD-naive patients (CAPEA), 50% presented with DAS28 > 5.1, 64% were ACPA/RF+, 13% had erosions, and 37% functional disability (FFbH < 70). In RABBIT, 63 (1(st) csDMARD failure) to 81% (>/=2 bDMARD failures) were ACPA/RF+, 29 to 70% had erosions, 33 to 52% DAS28 > 5.1, and 41 to 66% had FFbH < 70, respectively. In the NDB, between 47 (DMARD-naive) and 82% (>/=2 previous DMARDs) were ACPA/RF+, 5 to 11%, had high disease activity under treatment (DAS28 > 5.1), and 26 to 50% had functional disability (FFbH < 70), respectively. CONCLUSION: With growing numbers of previous DMARD therapies, increasing proportions of patients have poor prognostic factors. This underlines the importance of these factors for a difficult-to-treat disease course.

Authors: K. Albrecht, A. Richter, Y. Meissner, D. Huscher, L. Baganz, K. Thiele, M. Schneider, A. Strangfeld, A. Zink

Date Published: 2017

Publication Type: Journal

Verordnen wir ausreichend Physikalische Medizin? Aktuelle Daten aus der Kerndokumentation der Arbeitsgemeinschaft Regionaler Kooperativer Rheumazentren

Abstract

Not specified

Authors: K. Albrecht, D. Huscher

Date Published: 2017

Publication Type: Journal

Predictors of Reduced Health-Related Quality of Life in Adult Patients With Idiopathic Inflammatory Myopathies

Abstract (Expand)

OBJECTIVE: Extensive studies on health-related quality of life (HRQoL) in idiopathic inflammatory myopathies (IIMs) are lacking. Our objective was to document HRQoL and to identify factors associated … with a reduced HRQoL in patients with IIM. METHODS: A total of 1,715 patients (median age 49.9 years, 70% female, 87% white) who met probable or definite Bohan and Peter criteria or Griggs criteria for myositis were included from the Myovision registry. HRQoL was ascertained using the Short Form 12 (SF-12) health survey questionnaire. HRQoL physical component summary (PCS) and mental component summary (MCS) scores in relation to different patient and disease characteristics were compared to scores from matched normative data from the US general population and rheumatoid arthritis (RA) patients. Bivariate and multiple linear regression analyses were performed to assess the association between HRQoL and patient and disease parameters. RESULTS: The mean SF-12 summary scores were significantly lower in IIM patients than in the normative and RA populations. A diagnosis of inclusion body myositis, older age, patient-reported negative effect of disease on work, presence of another co-occurring autoimmune disease, polypharmacy, and IIM-associated lung disease and joint involvement were significantly associated with lower PCS scores. Lower MCS scores were associated with joint involvement and a negative effect of disease on work. CONCLUSION: In this large study of patient-reported outcomes in IIM, an association was found between multiple disease characteristics and reduced HRQoL, mostly in the physical domain. In the US, the HRQoL of IIM patients was found to be lower than that of the general population and RA patients.

Authors: M. Feldon, P. N. Farhadi, H. I. Brunner, L. Itert, B. Goldberg, A. Faiq, J. Wilkerson, K. M. Rose, L. G. Rider, F. W. Miller, E. H. Giannini

Date Published: 2017

Publication Type: Journal

2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups

Abstract (Expand)

OBJECTIVE: To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. METHODS: Candidate variables were assembled … from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria. RESULTS: Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of >/=90%, corresponding to a score of >/=7.5 (>/=8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of >/=50-<55% as "possible IIM." CONCLUSION: The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

Authors: I. E. Lundberg, A. Tjarnlund, M. Bottai, V. P. Werth, C. Pilkington, M. de Visser, L. Alfredsson, A. A. Amato, R. J. Barohn, M. H. Liang, J. A. Singh, R. Aggarwal, S. Arnardottir, H. Chinoy, R. G. Cooper, K. Danko, M. M. Dimachkie, B. M. Feldman, I. Garcia-De La Torre, P. Gordon, T. Hayashi, J. D. Katz, H. Kohsaka, P. A. Lachenbruch, B. A. Lang, Y. Li, C. V. Oddis, M. Olesinska, A. M. Reed, L. Rutkowska-Sak, H. Sanner, A. Selva-O’Callaghan, Y. W. Song, J. Vencovsky, S. R. Ytterberg, F. W. Miller, L. G. Rider, the Euromyositis Register International Myositis Classification Criteria Project Consortium, Study the Juvenile Dermatomyositis Cohort Biomarker, Repository

Date Published: 2017

Publication Type: Journal

Incidence and Mortality of Physician-Diagnosed Primary Sjogren Syndrome: Time Trends Over a 40-Year Period in a Population-Based US Cohort

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OBJECTIVE: To estimate the incidence and mortality rates, and their evolution over time, of physician-diagnosed primary Sjogren syndrome (pSS) in residents of Olmsted County, Minnesota. PATIENTS AND … METHODS: Medical records of patients with a diagnosis or suspicion of SS in Olmsted County from January 1, 2006, through December 31, 2015, were reviewed to identify incident cases of pSS (defined by physician diagnosis). These cases were combined with those from a 1976 through 2005 incident cohort (n=111) from the same population. Incidence rates were age and sex adjusted to the 2010 US white population. Survival rates were compared with the expected rates in the population of Minnesota. RESULTS: With 61 incident cases of pSS diagnosed in Olmsted County from 2006 through 2015, the total cohort included 172 patients with incident pSS from 1976 through 2015. Of the 172 patients, 151 (88%) were women and 161 (94%) were white, with a mean +/- SD age at diagnosis of 58.3+/-16.7 years. The average age- and sex-adjusted annual incidence for 2006 through 2015 was 5.9 per 100,000 population (95% CI, 4.4-7.4 per 100,000 population), and the overall incidence for the entire period was 5.8 per 100,000 (95% CI, 4.9-6.6 per 100,000). The incidence increased with calendar time over the 40-year period (P=.005). There was no difference in mortality in the pSS cohort compared with expected (standardized mortality ratio, 1.15; 95% CI, 0.86-1.50). CONCLUSION: The average annual incidence of pSS in this population-based cohort was 5.8 per 100,000, with a progressive increase over the 40 years of the study. Overall survival of patients with pSS was not different from that of the general population.

Authors: G. Maciel, C. S. Crowson, E. L. Matteson, D. Cornec

Date Published: 2017

Publication Type: Journal

Prevalence of Primary Sjogren’s Syndrome in a US Population-Based Cohort

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OBJECTIVE: To report the point prevalence of primary Sjogren’s syndrome (SS) in the first US population-based study. METHODS: Cases of all potential primary SS patients living in Olmsted County, … Minnesota, on January 1, 2015, were retrieved using Rochester Epidemiology Project resources, and ascertained by manual medical records review. Primary SS cases were defined according to physician diagnosis. The use of diagnostic tests was assessed and the performance of classification criteria was evaluated. The number of prevalent cases in 2015 was also projected based on 1976-2005 incidence data from the same source population. RESULTS: A total of 106 patients with primary SS were included in the study: 86% were female, with a mean +/- SD age of 64.6 +/- 15.2 years, and a mean +/- SD disease duration of 10.5 +/- 8.4 years. A majority were anti-SSA positive (75%) and/or anti-SSB positive (58%), but only 22% met American-European Consensus Group or American College of Rheumatology criteria, because the other tests required for disease classification (ocular dryness objective assessment, salivary gland functional or morphologic tests, or salivary gland biopsy) were rarely performed in clinical practice. According to the physician diagnosis, the age- and sex-adjusted prevalence of primary SS was 10.3 per 10,000 inhabitants, but according to classification criteria, this prevalence was only 2.2 per 10,000. The analysis based on previous incidence data projected a similar 2015 prevalence rate of 11.0 per 10,000. CONCLUSION: The prevalence of primary SS in this geographically well-defined population was estimated to be between 2 and 10 per 10,000 inhabitants. Physicians rarely used tests included in the classification criteria to diagnose the disease in this community setting.

Authors: G. Maciel, C. S. Crowson, E. L. Matteson, D. Cornec

Date Published: 2017

Publication Type: Journal

Physical activity but not sedentary activity is reduced in primary Sjogren’s syndrome

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The aim of the study was to evaluate the levels of physical activity in individuals with primary Sjogren’s syndrome (PSS) and its relationship to the clinical features of PSS. To this cross-sectional … study, self-reported levels of physical activity from 273 PSS patients were measured using the International Physical Activity Questionnaire-short form (IPAQ-SF) and were compared with healthy controls matched for age, sex and body mass index. Fatigue and other clinical aspects of PSS including disease status, dryness, daytime sleepiness, dysautonomia, anxiety and depression were assessed using validated tools. Individuals with PSS had significantly reduced levels of physical activity [median (interquartile range, IQR) 1572 (594-3158) versus 3708 (1732-8255) metabolic equivalent of task (MET) x min/week, p < 0.001], but similar levels of sedentary activity [median (IQR) min 300 (135-375) versus 343 (223-433) (MET) x min/week, p = 0.532] compared to healthy individuals. Differences in physical activity between PSS and controls increased at moderate [median (IQR) 0 (0-480) versus 1560 (570-3900) MET x min/week, p < 0.001] and vigorous intensities [median (IQR) 0 (0-480) versus 480 (0-1920) MET x min/week, p < 0.001]. Correlation analysis revealed a significant association between physical activity and fatigue, orthostatic intolerance, depressive symptoms and quality of life. Sedentary activity did not correlate with fatigue. Stepwise linear regression analysis identified symptoms of depression and daytime sleepiness as independent predictors of levels of physical activity. Physical activity is reduced in people with PSS and is associated with symptoms of depression and daytime sleepiness. Sedentary activity is not increased in PSS. Clinical care teams should explore the clinical utility of targeting low levels of physical activity in PSS.

Authors: W. F. Ng, A. Miller, S. J. Bowman, E. J. Price, G. D. Kitas, C. Pease, P. Emery, P. Lanyon, J. Hunter, M. Gupta, I. Giles, D. Isenberg, J. McLaren, M. Regan, A. Cooper, S. A. Young-Min, N. McHugh, S. Vadivelu, R. J. Moots, D. Coady, K. MacKay, B. Dasgupta, N. Sutcliffe, M. Bombardieri, C. Pitzalis, B. Griffiths, S. Mitchell, S. T. Miyamoto, M. Trenell, U. K. Primary Sjogren’s Syndrome Registry

Date Published: 2017

Publication Type: Journal

Advancing the Development of Patient-reported Outcomes for Adult Myositis at OMERACT 2016: An International Delphi Study

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OBJECTIVE: To define a set of core patient-reported domains and respective instruments for use in idiopathic inflammatory myopathies (IIM). Previously, we reported a systematic literature review on … patient-reported outcomes (PRO) in IIM followed by conducting international focus groups to elicit patient perspectives of myositis symptoms and effects. METHODS: Based on qualitative content analysis of focus groups, an initial list of 26 candidate domains was constructed. We subsequently conducted an international modified Delphi survey to identify the importance of each of the 26 domains. Participants were asked to rate each domain on a scale of 0-10 (0 = not important, 10 = very important). RESULTS: In this first round of the Delphi survey, 643 patients participated from the United States (n = 543), Sweden (n = 49), and South Korea (n = 51). Of the 26 domains, 19 (73%) were rated of high importance (>/= 7/10). The top 5 domains were muscle symptoms, fatigue, interactions with healthcare, medication side effects, and pain. During Outcome Measures in Rheumatology (OMERACT) 2016, we discussed the goal for ultimate reduction in the number of domains and the importance of considering representation of healthcare providers from other specialties, caregivers, representatives of pharmaceutical industries, and regulatory authorities in the next rounds of Delphi to represent broader perspectives on IIM. CONCLUSION: Further prioritization and a reduction in the number of domains will be needed for the next Delphi. At the next biennial OMERACT meeting, we aim to present and seek voting on a Myositis Preliminary PRO Core Set to enable ultimate measure selection and development.

Authors: J. K. Park, C. A. Mecoli, H. Alexanderson, M. Regardt, L. Christopher-Stine, M. Casal-Dominguez, I. de Groot, C. Sarver, I. E. Lundberg, C. O. Bingham, Y. W. Song

Date Published: 2017

Publication Type: Journal

[The first biologic for rheumatoid arthritis: factors influencing the therapeutic decision]

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BACKGROUND AND AIMS: Biologics (disease modifying antirheumatic drugs, bDMARD) have been in use in Germany for the treatment of rheumatoid arthritis (RA) since 2001, usually after failure of at least … one conventional synthetic (cs)DMARD. We analyzed temporal changes in factors that influence the decision for either a first bDMARD or a further csDMARD. MATERIAL AND METHODS: We analyzed data from 9513 bDMARD-naive RA patients in the German biologics register RABBIT who switched to a new therapy. For three recruitment periods (2001-2003, 2004-2006 and 2009-2015) factors influencing the therapeutic decision were analyzed by means of machine learning methods and logistic regression analysis. RESULTS: In all recruitment periods the number of previous csDMARDs, high dosages of glucocorticoids (>7.5 mg/day) and a higher DAS28 (>5.1) were significantly associated with the decision for a first bDMARD. Over time, the chance of receiving a bDMARD increased in patients with moderate disease activity, moderate glucocorticoid dosages (5-7.5 mg/day) and those with comorbidities, such as congestive heart failure or prior malignancy. Men had a higher chance of receiving a bDMARD than women only in the first recruitment period. Private health insurance, high education and gainful employment were significantly associated with more frequent prescription of bDMARDs in all recruitment periods. DISCUSSION: The time-dependent changes in the impact of disease activity, concomitant drugs, gender and comorbidity on the prescription of bDMARDs mirror the increasing therapeutic options and the growing experience in the application of the new substances in patients at higher risk. The influence of demographic and social factors may reflect safety concerns in patients at increased risk of adverse events but also the need to economize drug costs..

Authors: D. Pattloch, A. Richter, B. Manger, R. Dockhorn, L. Meier, H. P. Tony, A. Zink, A. Strangfeld

Date Published: 2017

Publication Type: Journal

The Diagnosis and Treatment of Sjogren’s Syndrome

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BACKGROUND: Sjogren’s syndrome is one of the more common inflammatory rheumatological diseases, with a prevalence of at least 0.4% in Germany. METHODS: This review is based on pertinent articles retrieved … by a selective search in PubMed. Special attention is drawn to updated classification criteria and current treatment recommendations. RESULTS: Sjogren’s syndrome has a wide variety of presentations, ranging from the local involvement of exocrine glands with keratoconjunctivitis sicca and xerostomia (the leading signs of the disease) to the systemic, extraglandular involvement of multiple organs. Fatigue also markedly worsens the patients’ quality of life. Serologic testing reveals antinuclear auto-antibodies (anti-Ro/ SSA and anti-La/SSB) as well as rheumatoid factors. The histological hallmark of the disease is focal lymphocytic infiltration in otherwise normal-appearing glandular acini. The disease also markedly elevates the risk of non-Hodgkin lymphoma of the B-cell series, which arises in about 5% of patients. Primary Sjogren’s syndrome (pSS) differs from the secondary form (sSS), which appears in the setting of another autoimmune disease, particularly systemic lupus erythematosus (15-36%), rheumatoid arthritis (20-32%), and limited or progressive systemic sclerosis (11-24%). Disease-modifying therapy is reserved for patients with systemic involvement; there is limited evidence for its efficacy. Because of the complexity of this disease, some of its clinical manifestations may require interdisciplinary treatment. CONCLUSION: The main considerations in the interdisciplinary care of patients with Sjogren’s disease are measures to improve quality of life, pharmacological and non-pharmacological treatments to keep disease activity in check, and management of the risk of lymphoma. Future therapeutic approaches must take the heterogeneity of the disease into account.

Authors: A. L. Stefanski, C. Tomiak, U. Pleyer, T. Dietrich, G. R. Burmester, T. Dorner

Date Published: 2017

Publication Type: Journal

Long-term glucocorticoid treatment in patients with polymyalgia rheumatica, giant cell arteritis, or both diseases: results from a national rheumatology database

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The objective of this study was to evaluate glucocorticoid (GC) use in patients with polymyalgia rheumatica (PMR), giant cell arteritis (GCA) or both diseases (PMR + GCA) under rheumatological care. … Data from patients with PMR (n = 1420), GCA (n = 177) or PMR + GCA (n = 261) from the National Database of the German Collaborative Arthritis Centers were analyzed regarding GCs and related comorbidities (osteoporosis, diabetes and cardiovascular disease), stratified by disease duration (DD). Longitudinal data were analyzed for all patients with a DD </= 2 years at database entry (n = 1397). Three-year data were available for 256 patients. Predictors of GC use >/= 3 years were examined by logistic regression analyses. A total of 76% received GCs, and 19% (PMR) to 40% (GCA) received methotrexate. Median GC doses were 12.5 mg (PMR), 11.3 mg (GCA), and 20.0 mg/day (PMR + GCA) in a 0-6-month DD. Median GC doses </= 5 mg/day were reached at a 13-18-month DD in PMR patients and at a 19-24-month DD in GCA or PMR + GCA patients. In the multivariate analysis, baseline methotrexate (OR 2.03, [95% CI 1.27-3.24]), GCs > 10 mg/day (OR 1.65, [1.07-2.55]), higher disease activity (OR 1.12, [1.02-1.23]) (median 0.6 years DD), and female sex (OR 1.63 [1.09-2.43]) were predictive for GC therapy at >/= 3 years. Of the examined comorbidities, only osteoporosis prevalence increased within 3 years. GC use for >/= 3 years was reported in one-fourth of all the patients. A difficult-to-control disease activity within the first year was a good predictor of long-term GC need.

Authors: K. Albrecht, D. Huscher, F. Buttgereit, M. Aringer, G. Hoese, W. Ochs, K. Thiele, A. Zink

Date Published: 2018

Publication Type: Journal

[Outpatient care and disease burden of rheumatoid arthritis : Results of a linkage of claims data and a survey of insured persons]

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BACKGROUND: Healthcare of patients with rheumatoid arthritis (RA) in Germany has mainly been evaluated in the past in RA cohorts from specialized arthritis centers. This study investigated rheumatological … care on a population basis, using claims data from a nationwide statutory health insurance fund (BARMER GEK) in combination with patient-reported outcomes from a questionnaire survey of insured persons with RA. METHODS: Data from insurants aged 18-79 years with M05 (seropositive RA) or M06 (other RA, ICD-10) diagnoses were analyzed concerning diagnostics, medication and prescribing physician. A 31-item questionnaire covering patient reported diagnosis, healthcare utilization and burden of illness was sent to a stratified random sample of 6193 insured persons. Data from the respondents regarding rheumatological care and disease status were evaluated. RESULTS: In 2013 and 2014, a total of 96,921 adults with M05 or M06 diagnosis were insured. The questionnaire was answered by 51% of the sample and of these 81% confirmed the RA diagnosis. RA had been diagnosed by a rheumatologist in 59% of the cases, 70% reported moderate to severe pain and 46% had functional disability. Between at least 40% (claims data) and up to 68% (respondents) were in specialized rheumatological care. Treatment with disease-modifying antirheumatic drugs (DMARDs) was 61% (claims data) and 63% (respondents) in persons in rheumatological care but only 18% outside rheumatological care. CONCLUSION: The results indicate that specialized rheumatological care is required to provide adequate treatment for patients with RA in Germany. Patients with higher age and patients with M06 diagnosis had less drug prescriptions and were less frequently treated by rheumatologists.

Authors: K. Albrecht, A. Luque Ramos, J. Callhoff, F. Hoffmann, K. Minden, A. Zink

Date Published: 2018

Publication Type: Journal

High prevalence of diabetes in patients with rheumatoid arthritis: results from a questionnaire survey linked to claims data

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OBJECTIVES: To investigate the prevalence of diabetes in patients with RA and the impact of diabetes on self-reported outcomes and health care. METHODS: RA patients between the ages of 18 and 79 years … were randomly selected from a nationwide statutory health insurance fund and were surveyed about rheumatological care and disease burden. Comorbid diabetes (E10-14) was analysed regarding age, sex, BMI and socioeconomic status. Disease burden, comorbidity and prescriptions were compared in RA patients with and without diabetes. Predictors of rheumatological care were identified by multivariate regression. RESULTS: Of the 2535 RA patients, 498 (20%) had diabetes. Diabetes was more frequent in males, in older patients, in patients with a higher BMI and in those with a lower socioeconomic status. All disease outcomes were poorer in RA-diabetes patients and were mainly attributable to a higher BMI. RA-diabetes patients received less DMARDs (40% vs 48%) and had more hospital stays (41% vs 30%) than patients without diabetes (all P < 0.05). Rates of cardiovascular disease (35% vs 15%), depression (39% vs 26%) and renal failure (23% vs 8%) were higher in RA-diabetes patients (all P < 0.0001). They were less frequently treated by rheumatology specialists: 57% vs 67%; odds ratio = 0.64 (95% CI: 0.45, 0.92), after controlling for confounders. CONCLUSION: The prevalence of diabetes in patients with RA is high and is associated with known sociodemographic factors. More than 40% of patients with RA and diabetes were not under rheumatological care even though they reported a high disease burden, were frequently hospitalized and often presented with further comorbidities.

Authors: K. Albrecht, A. Luque Ramos, F. Hoffmann, I. Redeker, A. Zink

Date Published: 2018

Publication Type: Journal

Versorgungssituation der rheumatoiden Arthritis in Deutschland

Abstract

Not specified

Authors: K. Albrecht, A. Zink

Date Published: 2018

Publication Type: Journal

Current Treatment for Myositis

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PURPOSE OF REVIEW: The purpose of this review was to give an update on treatment modalities for patients with idiopathic inflammatory myopathies, or shortly myositis, excluding the subgroup inclusion … body myositis, based on a literature survey on therapies used in myositis. Few controlled trials have been performed in patients with myositis; therefore, we also included a summary of open-label trials, case series, and case reports. RECENT FINDINGS: Glucocorticoid (GC) in high doses is still the first-line treatment of patients with myositis. There is a general recommendation to combine GCs with another immunosuppressive agent in the early phase of disease to better control disease activity and possibly to reduce the risk for GC-related side effects. Furthermore, combining pharmacological treatment with individualized and supervised exercise can be recommended based on evidence. There is some evidence for the effect of rituximab in patients with certain myositis-specific autoantibodies, whereas other biologic agents are currently being tested in clinical trials. SUMMARY: Immunosuppressive treatment in combination with exercise is recommended for patients with myositis to reduce disease activity and improve muscle performance. Subgrouping of patients into clinical and serological subtypes may be a way to identify biomarkers for response to specific immunosuppressive and biological agents and should be considered in future trials.

Authors: S. Barsotti, I. E. Lundberg

Date Published: 2018

Publication Type: Journal

[S2e guideline: treatment of rheumatoid arthritis with disease-modifying drugs]

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BACKGROUND: Medication-based strategies to treat rheumatoid arthritis are crucial in terms of outcome. They aim at preventing joint destruction, loss of function and disability by early and consistent … inhibition of inflammatory processes. OBJECTIVE: Achieving consensus about evidence-based recommendations for the treatment of rheumatoid arthritis with disease-modifying anti-rheumatic drugs in Germany. METHODS: Following a systematic literature research, a structured process among expert rheumatologists was used to reach consensus. RESULTS: The results of the consensus process can be summed up in 6 overarching principles and 10 recommendations. There are several new issues compared to the version of 2012, such as differentiated adjustments to the therapeutic regime according to time point and extent of treatment response, the therapeutic goal of achieving remission as assessed by means of the simplified disease activity index (SDAI) as well as the potential use of targeted synthetic DMARDs (JAK inhibitors) and suggestions for a deescalating in case of achieving a sustained remission. Methotrexate still plays the central role at the beginning of the treatment and as a combination partner in the further treatment course. When treatment response to methotrexate is inadequate, either switching to or combining with another conventional synthetic DMARD is an option in the absence of unfavourable prognostic factors. Otherwise biologic or targeted synthetic DMARDs are recommended according to the algorithm. Rules for deescalating treatment with glucocorticoids and-where applicable-DMARDs give support for the management of patients who have reached a sustained remission. DISCUSSION: The new guidelines set up recommendations for RA treatment in accordance with the treat-to-target principle. Modern disease-modifying drugs, now including also JAK inhibitors, are available in an algorithm.

Authors: C. Fiehn, J. Holle, C. Iking-Konert, J. Leipe, C. Weseloh, M. Frerix, R. Alten, F. Behrens, C. Baerwald, J. Braun, H. Burkhardt, G. Burmester, J. Detert, M. Gaubitz, A. Gause, E. Gromnica-Ihle, H. Kellner, A. Krause, J. Kuipers, H. M. Lorenz, U. Muller-Ladner, M. Nothacker, H. Nusslein, A. Rubbert-Roth, M. Schneider, H. Schulze-Koops, S. Seitz, H. Sitter, C. Specker, H. P. Tony, S. Wassenberg, J. Wollenhaupt, K. Kruger

Date Published: 2018

Publication Type: Journal

Treatment Patterns of Newly Diagnosed Rheumatoid Arthritis Patients from a Commercially Insured Population

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INTRODUCTION: To describe treatment patterns in newly diagnosed rheumatoid arthritis (RA) patients in a large, nationally representative managed-care database. METHODS: Newly diagnosed RA patients were … identified from 07/01/2006-08/31/2014. Patients had >/= 1 RA diagnosis by a rheumatologist, or >/= 2 non-rheumatologist RA diagnoses >/= 30 days apart, or RA diagnosis followed by a disease-modifying antirheumatic drug (DMARD) prescription fill within 1 year. Patients were >/= 18 years old at index (earliest date fulfilling diagnostic criteria) and had >/= 6 and 12 months of pre- and post-index health plan enrollment, respectively. Patterns of DMARD treatment, including conventional synthetic DMARDs (csDMARD), tumor necrosis factor inhibitors (TNFi), non-TNFi, and Janus kinase inhibitors (JAKi), were captured during follow-up. RESULTS: Of the 63,101 RA patients identified, 73% were female; mean age was 57 years. During an average of 3.5 +/- 2.1 years of follow-up, 45% of patients never received a DMARD, 52% received a csDMARD (94 +/- 298 mean +/- SD days from index), 16% a TNFi (315 +/- 448 days), 4% a non-TNFi (757 +/- 660 days), and < 1% a JAKi. Among DMARD recipients, the most common treatment patterns were: receiving csDMARDs only (68%), adding a TNFi as second-line therapy after initiation of a csDMARD (12%), and receiving only a TNFi (6%) during follow-up. Among those not on DMARDs, the all-cause usage of an opioid was 56% and 19% had chronic opioid use (>/= 180 days supplied). CONCLUSIONS: Despite American College of Rheumatology recommendations for DMARD treatment of RA, nearly half of newly diagnosed RA patients received no DMARD therapy during follow-up. These data identify a treatment gap in RA management. FUNDING: Eli Lilly & Company.

Authors: D. M. Kern, L. Chang, K. Sonawane, C. J. Larmore, N. N. Boytsov, R. A. Quimbo, J. Singer, J. T. Hinton, S. J. Wu, A. B. Araujo

Date Published: 2018

Publication Type: Journal

The EuroMyositis registry: an international collaborative tool to facilitate myositis research

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AIMS: The EuroMyositis Registry facilitates collaboration across the idiopathic inflammatory myopathy (IIM) research community. This inaugural report examines pooled Registry data. METHODS: Cross-sectional … analysis of IIM cases from 11 countries was performed. Associations between clinical subtypes, extramuscular involvement, environmental exposures and medications were investigated. RESULTS: Of 3067 IIM cases, 69% were female. The most common IIM subtype was dermatomyositis (DM) (31%). Smoking was more frequent in connective tissue disease overlap cases (45%, OR 1.44, 95% CI 1.09 to 1.90, p=0.012). Smoking was associated with interstitial lung disease (ILD) (OR 1.32, 95% CI 1.06 to 1.65, p=0.013), dysphagia (OR 1.43, 95% CI 1.16 to 1.77, p=0.001), malignancy ever (OR 1.78, 95% CI 1.36 to 2.33, p<0.001) and cardiac involvement (OR 2.40, 95% CI 1.60 to 3.60, p<0.001).Dysphagia occurred in 39% and cardiac involvement in 9%; either occurrence was associated with higher Health Assessment Questionnaire (HAQ) scores (adjusted OR 1.79, 95% CI 1.43 to 2.23, p<0.001). HAQ scores were also higher in inclusion body myositis cases (adjusted OR 3.85, 95% CI 2.52 to 5.90, p<0.001). Malignancy (ever) occurred in 13%, most commonly in DM (20%, OR 2.06, 95% CI 1.65 to 2.57, p<0.001).ILD occurred in 30%, most frequently in antisynthetase syndrome (71%, OR 10.7, 95% CI 8.6 to 13.4, p<0.001). Rash characteristics differed between adult-onset and juvenile-onset DM cases (’V’ sign: 56% DM vs 16% juvenile-DM, OR 0.16, 95% CI 0.07 to 0.36, p<0.001). Glucocorticoids were used in 98% of cases, methotrexate in 71% and azathioprine in 51%. CONCLUSION: This large multicentre cohort demonstrates the importance of extramuscular involvement in patients with IIM, its association with smoking and its influence on disease severity. Our findings emphasise that IIM is a multisystem inflammatory disease and will help inform prognosis and clinical management of patients.

Authors: J. B. Lilleker, J. Vencovsky, G. Wang, L. R. Wedderburn, L. P. Diederichsen, J. Schmidt, P. Oakley, O. Benveniste, M. G. Danieli, K. Danko, N. T. P. Thuy, M. Vazquez-Del Mercado, H. Andersson, B. De Paepe, J. L. deBleecker, B. Maurer, L. J. McCann, N. Pipitone, N. McHugh, Z. E. Betteridge, P. New, R. G. Cooper, W. E. Ollier, J. A. Lamb, N. S. Krogh, I. E. Lundberg, H. Chinoy, contributors all EuroMyositis

Date Published: 2018

Publication Type: Journal

Patterns of the initiation of disease-modifying antirheumatic drugs in incident rheumatoid arthritis: a German perspective based on nationwide ambulatory drug prescription data

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This study aimed at providing a current and nearly complete picture of the patterns of the initiation of disease-modifying antirheumatic drugs (DMARDs) in patients with newly diagnosed RA. Based on … ambulatory drug prescription data and physician billing claims data covering 87% of the German population, we assembled a cohort of incident RA patients aged 15-79 years (n = 54,896) and assessed the prescription frequency of total DMARDs, conventional synthetic (csDMARDs) and biologic DMARDs (bDMARDs) within the first year of disease. Using multiple logistic regression, we estimated the chance of early DMARD receipt based on age, sex, serotype and specialty of prescribing physician while controlling for region of residence. In total, 44% of incident RA patients received a DMARD prescription within the first year of disease. In multiple regression, younger patients (< 35 years) had 1.7-fold higher chances of receiving a csDMARD than patients aged >/= 65 years [odds ratio (OR): 1.65 with 95% confidence interval (CI) 1.51-1.80] and almost tenfold higher chances to receive a bDMARD [OR (95% CI) 9.5 (8.0-11.3)]. Seropositivity and a visit to a rheumatologist were positively associated with DMARD initiation [OR (95% CI) 2.8 (2.6-2.9) and 5.9 (5.6-6.2) for csDMARDs, respectively]. Based on data covering 87% of the German population, the present study revealed that less than half of incident RA patients receive DMARDs within the first year of disease and that marked differences exist according to age. The study highlights the importance of involving a rheumatologist early in the management of RA.

Authors: A. Steffen, J. Holstiege, K. Klimke, M. K. Akmatov, J. Batzing

Date Published: 2018

Publication Type: Journal

[Long-term trends in rheumatology care : Achievements and deficits in 25 years of the German national rheumatology database]

Abstract (Expand)

BACKGROUND: Since 1993, data on the care and quality of life of patients with inflammatory rheumatic diseases have been collected in the German National Database (NDB) of the regional collaborative … rheumatology centers. OBJECTIVE: In this review long-term trends on treatment, disease activity and gainful employment of the most common inflammatory rheumatic diseases are presented and the most important analyses from 25 years of the NDB are summarized. METHODS: Between 15 and 17 rheumatological institutions take part in the core documentation and once a year collect data from a total of more than 10,000 patients. The rheumatologists document the disease status and care, the patients report on their state of health and the effects of the disease. RESULTS: The biologics era at the beginning of the twenty-first century has led to changes in the therapeutic spectrum of most inflammatory rheumatic diseases, especially in rheumatoid arthritis and ankylosing spondylitis. Some basic therapies formerly used are hardly used anymore and glucocorticoids are used less frequently. Methotrexate has remained the standard therapy for rheumatoid arthritis over the years. Nowadays, nearly 30% of patients with rheumatoid arthritis receive treatment with biologics. Disease activity, functional and social restrictions have decreased across all diseases. CONCLUSION: The improved health status of many patients with rheumatic diseases confirms the high level of care provided by the rheumatism centers involved in the NDB. The increasing specification of measuring instruments and the standardization of documentation systems are major challenges that the NDB will have to face in the coming years if it is to remain in the digital age.

Authors: K. Albrecht, J. Callhoff, A. Zink

Date Published: 2019

Publication Type: Journal

Trends in employment and hospitalisation in patients with Sjogren’s syndrome 1996-2016: results from the German National database

Abstract (Expand)

OBJECTIVES: To assess trends in treatments and outcomes in patients with primary Sjogren’s syndrome (pSS), focusing on employment, hospitalisation and medical treatment in the past two decades. METHODS: … From 1996 to 2016, approximately 300 patients with pSS were annually documented in the National Database of the German Collaborative Arthritis Centres. Data on treatment, physicians’ assessments of disease activity, patient-reported outcomes, hospitalisation and employment were collected and compared to patients with rheumatoid arthritis (RA), matched 1:1 for age, sex and disease duration for each calendar year. RESULTS: Patients with pSS (>90% female, age 44 years at disease onset, disease duration 10 years) were more frequently assessed to be in low disease activity in 2016 (93%) than in 1996 (62%), p<0.01. Treatment with antimalarials increased from 1996 to 2016 (31 to 50%, p<0.01) and less patients were on glucocorticosteroids (50 to 34%, p<0.01) but <5% were treated with biologics. Employment (<65 years) increased by 21 percentage points (43 to 64%, p<0.001), exceeding the increase observed for RA patients (+15 percentage points). Early retirement (22 to 10%, p=0.01), hospitalisation/year (13 to 7%, p=0.08) and sick leave (39% in 1997 to 27%, p=0.09) decreased comparably to RA patients. CONCLUSIONS: Overall, similar trends were observed for RA and pSS cohorts despite minor changes in pSS therapy. Work participation has improved significantly over two decades in pSS. A greater perception of pSS without systemic manifestations may have caused a shift towards less severely affected patient cohorts today.

Authors: J. Callhoff, K. Thiele, T. Dorner, A. Zink, J. G. Richter, J. Henes, K. Albrecht

Date Published: 2019

Publication Type: Journal

[Non-drug treatment of rheumatoid arthritis : An analysis of claims data and a survey of insured persons (Project PROCLAIR)]

Abstract (Expand)

BACKGROUND: Only small amounts of data are available on the prescription frequency of physical therapies (PT) for patients with rheumatoid arthritis (RA). OBJECTIVE: The aim of the study was to evaluate … prescription frequencies of PT considering functional status and sociodemographic factors. MATERIAL AND METHODS: A total of 98,963 adults diagnosed with RA in 2013 were identified in claims data from the BARMER health insurance. A questionnaire was sent to a representative sample of 6193 people requesting information on the disease status. Of these 2535 persons were included who agreed to the linking of the questionnaire and claims data and who confirmed a diagnosis of RA. From the routine claims data the prescription of PT and occupational therapy as well as the medical discipline of the prescribing physician were analyzed. Multivariable logistic regression was conducted to determine which variables (age, sex, M05/M06 diagnosis, residential area, income, functional status and rheumatological care) were associated with the use of PT. RESULTS: In 2015 a total of 47% of the study population received PT (35% physiotherapy, 15% thermotherapy, 15% manual therapy, 2% electrotherapy and 6% massage) and 3% occupational therapy. Of the PT prescriptions 37% were issued by general practitioners, 27% by orthopedists and 18% by rheumatologists. Women and persons living in the eastern states of Germany and patients with high functional impairment were prescribed PT more often. Income, educational status, seropositivity and rheumatological care did not have any influence on the frequency of prescription of PT. CONCLUSION: There are deficits in the outpatient prescription of PT but without indications of an undersupply of population groups due to low socioeconomic status. In contrast to the prescription of disease-modifying antirheumatic drug (DMARD) treatment, PT is predominantly prescribed by general practitioners.

Authors: H. Jacobs, J. Callhoff, F. Hoffmann, A. Zink, K. Albrecht

Date Published: 2019

Publication Type: Journal

Comorbidities in Patients with Rheumatoid Arthritis and Their Association with Patient-reported Outcomes: Results of Claims Data Linked to Questionnaire Survey

Abstract (Expand)

OBJECTIVE: To investigate the prevalence of comorbidities in a population-based cohort of persons with rheumatoid arthritis (RA) compared to matched controls and to examine their association with … patient-reported outcomes in a survey sample. METHODS: Data of 96,921 persons with RA [International Classification of Diseases, 10th ed (ICD-10) M05/M06] and 484,605 age- and sex-matched controls without RA of a German statutory health fund were studied regarding 26 selected comorbidities (ICD-10). A self-reported questionnaire, comprising joint counts [(tender joint count (TJC), swollen joint count (SJC)], functional status (Hannover Functional Ability Questionnaire), effect of the disease (Rheumatoid Arthritis Impact of Disease), and well-being (World Health Organization 5-item Well-Being Index; WHO-5) was sent to a random sample of 6193 persons with RA, of whom 3184 responded. For respondents who confirmed their RA (n = 2535), associations between comorbidities and patient-reported outcomes were analyzed by multivariable linear regression. RESULTS: Compared to controls, all investigated comorbidities were more frequent in persons with RA (mean age 63 yrs, 80% female). In addition to cardiovascular risk factors, the most common were osteoarthritis (44% vs 21%), depression (32% vs 20%), and osteoporosis (26% vs 9%). Among the survey respondents, 87% of those with 0-1 comorbidity but only 77% of those with >/= 8 comorbidities were treated by rheumatologists. Increasing numbers of comorbidities were associated with poorer values for TJC, SJC, function, and WHO-5. CONCLUSION: Compared to a matched population, persons with RA present with increased prevalence of numerous comorbidities. Patients with RA and multimorbidity are at risk of insufficient rheumatological care and poorer patient-reported outcomes.

Authors: A. Luque Ramos, I. Redeker, F. Hoffmann, J. Callhoff, A. Zink, K. Albrecht

Date Published: 2019

Publication Type: Journal

Perceptions of Patients, Caregivers, and Healthcare Providers of Idiopathic Inflammatory Myopathies: An International OMERACT Study

Abstract (Expand)

OBJECTIVE: Patient-reported outcome measures (PROM) that incorporate the patient perspective have not been well established in idiopathic inflammatory myopathies (IIM). As part of our goal to develop … IIM-specific PROM, the Outcome Measures in Rheumatology (OMERACT) Myositis special interest group sought to determine which aspects of disease and its effects are important to patients and healthcare providers (HCP). METHODS: Based on a prior qualitative content analysis of focus groups, an initial list of 24 candidate domains was constructed. We subsequently conducted an international survey to identify the importance of each of the 24 domains to be assessed in clinical research. Patients with IIM, their caregivers, and HCP treating IIM completed the survey. RESULTS: In this survey, a total of 638 respondents completed the survey, consisting of 510 patients, 101 HCP, and 27 caregivers from 48 countries. Overall, patients were more likely to rank "fatigue," "cognitive impact," and "difficulty sleeping" higher compared with HCP, who ranked "joint symptoms," "lung symptoms," and "dysphagia" higher. Both patients and providers rated muscle symptoms as their top domain. In general, patients from different countries were in agreement on which domains were most important. One notable exception was that patients from Sweden and the Netherlands ranked lung symptoms significantly higher compared to other countries including the United States and Australia (mean weighted rankings of 2.86 and 2.04 vs 0.76 and 0.80, respectively; p < 0.0001). CONCLUSION: Substantial differences exist in how IIM is perceived by patients compared to HCP, with different domains prioritized. In contrast, patients’ ratings across the world were largely similar.

Authors: C. A. Mecoli, J. K. Park, H. Alexanderson, M. Regardt, M. Needham, I. de Groot, C. Sarver, I. E. Lundberg, B. Shea, M. de Visser, Y. W. Song, C. O. Bingham, L. Christopher-Stine

Date Published: 2019

Publication Type: Journal

OMERACT 2018 Modified Patient-reported Outcome Domain Core Set in the Life Impact Area for Adult Idiopathic Inflammatory Myopathies

Abstract (Expand)

OBJECTIVE: To present and vote on a myositis modified patient-reported outcome core domain set in the life impact area at the Outcome Measures in Rheumatology (OMERACT) 2018. METHODS: Based on results … from international focus groups and Delphi surveys, a draft core set was developed. RESULTS: Domains muscle symptoms, fatigue, level of physical activity, and pain reached >/= 70% consensus and were mandatory to assess in all trials. Domains lung, joint, and skin symptoms were mandatory in specific circumstances. This core set was endorsed by > 85% at OMERACT 2018. CONCLUSION: We propose a life impact core set for patients with idiopathic inflammatory myopathies and will proceed with instrument selections.

Authors: M. Regardt, C. A. Mecoli, J. K. Park, I. de Groot, C. Sarver, M. Needham, M. de Visser, B. Shea, C. O. Bingham, I. E. Lundberg, Y. W. Song, L. Christopher-Stine, H. Alexanderson

Date Published: 2019

Publication Type: Journal

[Sjogren’s syndrome]

Abstract (Expand)

The prevalence of primary Sjogren’s syndrome (pSS) is between 1:100 and 1:1000 and it is therefore the most common connective tissue disease. Nevertheless, it can be difficult to diagnose pSS as the … symptoms are frequently unspecific and diagnostic markers are lacking in many patients. In addition, only few controlled therapeutic studies of pSS have been carried out so that the optimal management is not yet clear. Meanwhile, outcome parameters to monitor clinical improvement have been developed and a large number of therapeutic studies are currently being performed. This review article summarizes the current diagnostic and treatment options for pSS.

Author: T. Witte

Date Published: 2019

Publication Type: Journal

[Is the prevalence of rheumatoid arthritis truly on the rise?]

Abstract (Expand)

A growing number of health insurance data analyses show an increase in the prevalence of rheumatoid arthritis (RA) in Germany. The studies refer to the claims diagnosis of RA, which is more frequent … in recent years compared to earlier periods. Depending on the case definition, the numbers vary between 0.6% and 1.4% of the adult population. In this paper, the different studies are reviewed with regard to their data sources, the case definitions of RA and the frequency of the diagnosis. Due to the lack of clinical validation, the prevalence cannot be precisely determined from claims data.

Authors: K. Albrecht, J. Callhoff, A. Strangfeld

Date Published: 2022

Publication Type: Journal

Body mass index distribution in rheumatoid arthritis: a collaborative analysis from three large German rheumatoid arthritis databases

Abstract (Expand)

BACKGROUND: METARTHROS (Metabolic impact on joint and bone disease) is a nationwide German network to investigate the overlap between inflammatory and metabolic diseases. The objective of this study … was to compare the body mass index (BMI) distribution in patients with early and established rheumatoid arthritis (RA) with data from the general population, and to evaluate the association of BMI with patient characteristics and clinical markers. METHODS: The BMI distribution was examined with data collected at inclusion of patients in the early arthritis cohort CAPEA, the biologics register RABBIT, and the National database of the German Collaborative Arthritis Centers. A data source with a representative sample of the German population (German Ageing Survey) was used as a comparator. BMI categories of <18.5 kg/m(2) (underweight), 18.5 to <25 kg/m(2) (normal weight), 25 to <30 kg/m(2) (overweight), and >/=30 kg/m(2) (obese) were used. Patients were stratified by age and sex, and compared to controls from the German Ageing Survey. Associations between BMI and markers of disease activity were analysed with non-parametric tests and linear models. RESULTS: Data from 1207 (CAPEA), 12,230 (RABBIT), and 3424 (National database) RA patients and 6202 population controls were evaluated. The mean age was 56, 56, 62, and 62 years, respectively, the mean disease duration was 13 weeks, 9.9 years, and 13.5 years, respectively, and the mean disease activity score (DAS28) was 5.1, 5.2, and 3.1, respectively. In all RA cohorts, obesity was more frequent (23.8 %, 23.4 %, 21.4 %, respectively) than in controls (18.2 %). This applied to all age groups <70 years, was independent of disease duration, and was more pronounced in females. In all cohorts, the age at RA onset was associated with BMI, being higher in overweight/obese patients compared to normal-weight patients. Current smoking was negatively associated with BMI. Linear analyses revealed increased erythrocyte sedimentation rate (ESR) values in underweight and obese females, and an increasing disparity between tender joint counts (TJCs) and swollen joint counts (SJCs) in higher BMI categories. CONCLUSIONS: Compared to the general population, a higher prevalence of obesity was observed in all RA cohorts. The dominance of obesity in females and the different behaviour of disease activity markers in relation to the BMI in females indicate that additional parameters need to be considered when analysing the impact of obesity on inflammation in RA.

Authors: K. Albrecht, A. Richter, J. Callhoff, D. Huscher, G. Schett, A. Strangfeld, A. Zink

Date Published: 2016

Publication Type: Journal

[How frequent are poor prognostic markers in rheumatoid arthritis? : An estimate based on three epidemiologic cohorts]

Abstract (Expand)

BACKGROUND: Unfavorable prognostic factors-high disease activity, early erosions, and autoantibodies-should be considered when making treatment decisions in rheumatoid arthritis (RA). There are little … data on the frequency of individual poor prognostic factors among RA patients in daily care. METHODS: Disease activity (Disease Activity Score, DAS28), erosions, antibodies against citrullinated peptides or rheumatoid factor (ACPA/RF+), previous treatment failure, inflammation markers, and functional disability (FFbH < 70) were defined as prognostic factors. Different treatment decision making situations were evaluated in disease-modifying antirheumatic drug (DMARD)-naive patients from the early RA CAPEA cohort (n = 1059), and in patients from the biologics register RABBIT after failure of one (n = 2217) or more (n = 3280) conventional synthetic (cs)DMARDs or one (n = 1134) or more (n = 795) biologic (b)DMARDs. With the national database of German arthritis centers (NDB), the frequency of these factors was analyzed according to treatment strata (no/1(st)/2(nd)/3(rd) DMARD; n = 5707). RESULTS: In DMARD-naive patients (CAPEA), 50% presented with DAS28 > 5.1, 64% were ACPA/RF+, 13% had erosions, and 37% functional disability (FFbH < 70). In RABBIT, 63 (1(st) csDMARD failure) to 81% (>/=2 bDMARD failures) were ACPA/RF+, 29 to 70% had erosions, 33 to 52% DAS28 > 5.1, and 41 to 66% had FFbH < 70, respectively. In the NDB, between 47 (DMARD-naive) and 82% (>/=2 previous DMARDs) were ACPA/RF+, 5 to 11%, had high disease activity under treatment (DAS28 > 5.1), and 26 to 50% had functional disability (FFbH < 70), respectively. CONCLUSION: With growing numbers of previous DMARD therapies, increasing proportions of patients have poor prognostic factors. This underlines the importance of these factors for a difficult-to-treat disease course.

Authors: K. Albrecht, A. Richter, Y. Meissner, D. Huscher, L. Baganz, K. Thiele, M. Schneider, A. Strangfeld, A. Zink

Date Published: 2017

Publication Type: Journal

[Risk profile of disease-modifying antirheumatic drugs: an update from the RABBIT register]

Abstract (Expand)

This article provides an overview of current results from the German biologics register RABBIT on the safety of biologic and targeted synthetic disease-modifying antirheumatic drugs in rheumatoid … arthritis. Collaborative data from the European biologics registries show no evidence for an overall increased risk of malignancy with TNF inhibitors. Venous thromboembolism occurs less frequently under TNF inhibitors than under conventional synthetic DMARDs. Regarding interleukin-6 inhibitors, the incidence of lower intestinal tract perforations is increased with tocilizumab and presents with atypical symptoms. There is no evidence of increased facial paresis with tocilizumab. Janus kinase inhibitors increase the risk for the occurrence of herpes zoster. New data on biosimilars suggest that they can be used with a comparable safety profile to originator drugs.

Authors: K. Albrecht, A. Strangfeld

Date Published: 2021

Publication Type: Journal

[Gender-specific differences in the diagnosis and treatment of inflammatory rheumatic diseases]

Abstract (Expand)

BACKGROUND: Gender differences in the diagnosis and treatment of various diseases are increasingly being researched with the aim of optimizing treatment strategies and improving individual treatment … success. METHODS: This paper summarizes the existing literature for gender differences in inflammatory rheumatic diseases. RESULTS: Many, but not all, inflammatory rheumatic diseases occur more frequently in women than in men. Women more often have a longer duration of symptoms until diagnosis than men, which may be due to different clinical and radiological presentations. Across diseases, women more often have lower remission and treatment response rates to antirheumatic medication compared to men. Discontinuation rates are also higher in women than in men. Whether women are more likely to develop anti-drug antibodies to biologic disease-modifying antirheumatic drugs is still unclear. For Janus kinase inhibitors, there is no evidence of differential treatment response to date. CONCLUSION: Whether individual dosing regimens and gender-adapted remission criteria are also required in rheumatology cannot be deduced from the evidence available to date.

Authors: K. Albrecht, A. Strangfeld

Date Published: 2023

Publication Type: Journal

Consensus statement on blocking interleukin-6 receptor and interleukin-6 in inflammatory conditions: an update

Abstract (Expand)

BACKGROUND: Targeting interleukin (IL)-6 has become a major therapeutic strategy in the treatment of immune-mediated inflammatory disease. Interference with the IL-6 pathway can be directed at the … specific receptor using anti-IL-6Ralpha antibodies or by directly inhibiting the IL-6 cytokine. This paper is an update of a previous consensus document, based on most recent evidence and expert opinion, that aims to inform on the medical use of interfering with the IL-6 pathway. METHODS: A systematic literature research was performed that focused on IL-6-pathway inhibitors in inflammatory diseases. Evidence was put in context by a large group of international experts and patients in a subsequent consensus process. All were involved in formulating the consensus statements, and in the preparation of this document. RESULTS: The consensus process covered relevant aspects of dosing and populations for different indications of IL-6 pathway inhibitors that are approved across the world, including rheumatoid arthritis, polyarticular-course and systemic juvenile idiopathic arthritis, giant cell arteritis, Takayasu arteritis, adult-onset Still’s disease, Castleman’s disease, chimeric antigen receptor-T-cell-induced cytokine release syndrome, neuromyelitis optica spectrum disorder and severe COVID-19. Also addressed were other clinical aspects of the use of IL-6 pathway inhibitors, including pretreatment screening, safety, contraindications and monitoring. CONCLUSIONS: The document provides a comprehensive consensus on the use of IL-6 inhibition to treat inflammatory disorders to inform healthcare professionals (including researchers), patients, administrators and payers.

Authors: D. Aletaha, A. Kerschbaumer, K. Kastrati, C. Dejaco, M. Dougados, I. B. McInnes, N. Sattar, T. A. Stamm, T. Takeuchi, M. Trauner, D. van der Heijde, M. Voshaar, K. L. Winthrop, A. Ravelli, N. Betteridge, G. R. Burmester, J. W. Bijlsma, V. Bykerk, R. Caporali, E. H. Choy, C. Codreanu, B. Combe, M. K. Crow, M. de Wit, P. Emery, R. M. Fleischmann, C. Gabay, M. L. Hetland, K. L. Hyrich, A. Iagnocco, J. D. Isaacs, J. M. Kremer, X. Mariette, P. A. Merkel, E. F. Mysler, P. Nash, M. T. Nurmohamed, K. Pavelka, G. Poor, A. Rubbert-Roth, H. Schulze-Koops, A. Strangfeld, Y. Tanaka, J. S. Smolen

Date Published: 2023

Publication Type: Journal

Integrated proteomics and genomics analysis of paradoxical eczema in psoriasis patients treated with biologics

Abstract (Expand)

BACKGROUND: Few studies have explored the immunology and genetic risk of paradoxical eczema occurring as an adverse event of biologic therapy in patients with psoriasis. OBJECTIVES: We sought to describe … the systemic inflammatory signature of paradoxical eczema using proteomics and explore whether this is genetically mediated. METHODS: This study used the Olink Target 96 Inflammation panel on 256 serum samples from 71 patients with psoriasis and paradoxical eczema, and 75 controls with psoriasis to identify differentially expressed proteins and enriched gene sets. Case samples from 1 or more time points (T1 prebiologic, T2 postbiologic, and T3 postparadoxical eczema) were matched 1:1 with control samples. Genes contributing to enriched gene sets were selected, and functional single nucleotide polymorphisms used to create polygenic risk scores in a genotyped cohort of 88 paradoxical eczema cases and 3124 psoriasis controls. RESULTS: STAMBP expression was lower in cases at T1 than in controls (log-fold change: -0.44; adjusted P = .022); no other proteins reached statistical significance at equivalent time points. Eleven gene sets including cytokine and chemokine pathways were enriched in cases at T2 and 10 at T3. Of the 39 proteins contributing to enriched gene sets, the majority are associated with the atopic dermatitis serum proteome. A polygenic risk score including 38 functional single nucleotide polymorphisms linked to enriched gene sets was associated with paradoxical eczema (adjusted P = .046). CONCLUSIONS: The paradoxical eczema systemic inflammatory proteome trends toward atopic dermatitis at a gene-set level and is detectable before onset of the phenotype. This signature could be genetically determined.

Authors: A. Al-Janabi, P. Martin, A. R. Khan, A. C. Foulkes, C. H. Smith, C. E. M. Griffiths, A. P. Morris, S. Eyre, R. B. Warren, Bstop Study Group, Badbir Study Group the

Date Published: 2023

Publication Type: Journal

Current state of evidence on ’off-label’ therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland–a consensus report

Abstract (Expand)

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only … glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include ’off-label’ use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors’ own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

Authors: M. Aringer, H. Burkhardt, G. R. Burmester, R. Fischer-Betz, M. Fleck, W. Graninger, F. Hiepe, A. M. Jacobi, I. Kotter, H. J. Lakomek, H. M. Lorenz, B. Manger, G. Schett, R. E. Schmidt, M. Schneider, H. Schulze-Koops, J. S. Smolen, C. Specker, T. Stoll, A. Strangfeld, H. P. Tony, P. M. Villiger, R. Voll, T. Witte, T. Dorner

Date Published: 2012

Publication Type: Journal

Characterization of patients with psoriatic arthritis in dermatologic and rheumatologic care: analysis of two registries

Abstract (Expand)

BACKGROUND AND OBJECTIVE: Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease affecting the musculoskeletal system, skin and nails. The aim is to characterize sociodemographic and … clinical patient profiles documented in dermatologic and rheumatologic care. PATIENTS AND METHODS: Data of 704 patients with PsA from the dermatological Psoriasis Registry PsoBest (PB) and 1066 patients from the rheumatological disease registry RABBIT-SpA (RS) were analyzed. Comparable anamnestic and clinical variables were identified and descriptively analyzed. RESULTS: The mean age was 51.7 years in PB and 51.9 in RS. Disease duration of psoriasis was longer, mean cutaneous severity was higher in PB. However, more patients in RS vs. PB had tender joints and swollen joints. Mean Dermatology Life Quality Index was higher in PB and mean Health Assessment Questionnaire in RS. Patient reported global disease activity and pain were lower in PB. IL-23 inhibitors were used more frequently in PB, and TNF inhibitors in RS. CONCLUSIONS: Clinical specialization was associated with different clinical and treatment patterns of PsA. This may indicate a selection by dominant manifestation of psoriatic disease and potentially by effects of health care access. Psoriatic arthritis should be treated in a multidisciplinary approach considering all facets of this complex disease.

Authors: M. Augustin, L. Lindner, L. Kuhl, A. Weiss, S. J. Rustenbach, B. Stephan, M. Feuchtenberger, U. Mrowietz, D. Thaci, P. Staubach, X. Baraliakos, A. Strangfeld, R. von Kiedrowski, F. Behrens, A. C. Regierer

Date Published: 2023

Publication Type: Journal

[Charakterisierung von Patienten mit Psoriasisarthritis in der dermatologischen und rheumatologischen Versorgung: Analyse von zwei Registern: Characterization of patients with psoriatic arthritis in dermatologic and rheumatologic care: analysis of two registries]

Abstract

Not specified

Authors: M. Augustin, L. Lindner, L. Kuhl, A. Weiss, S. J. Rustenbach, B. Stephan, M. Feuchtenberger, U. Mrowietz, D. Thaci, P. Staubach, X. Baraliakos, A. Strangfeld, R. von Kiedrowski, F. Behrens, A. C. Regierer

Date Published: 2023

Publication Type: Journal

Evaluation of discontinuation for adverse events of JAK inhibitors and bDMARDs in an international collaboration of rheumatoid arthritis registers (the ’JAK-pot’ study)

Abstract (Expand)

BACKGROUND: In a clinical trial setting, patients with rheumatoid arthritis (RA) taking the Janus kinase inhibitor (JAKi) tofacitinib demonstrated higher adverse events rates compared with those taking … the tumour necrosis factor inhibitors (TNFi) adalimumab or etanercept. OBJECTIVE: Compare treatment discontinuations for adverse events (AEs) among second-line therapies in an international real-world RA population. METHODS: Patients initiating JAKi, TNFi or a biological with another mode of action (OMA) from 17 registers participating in the ’JAK-pot’ collaboration were included. The primary outcome was the rate of treatment discontinuation due to AEs. We used unadjusted and adjusted cause-specific Cox proportional hazard models to compare treatment discontinuations for AEs among treatment groups by class, but also evaluating separately the specific type of JAKi. RESULTS: Of the 46 913 treatment courses included, 12 523 were JAKi (43% baricitinib, 40% tofacitinib, 15% upadacitinib, 2% filgotinib), 23 391 TNFi and 10 999 OMA. The adjusted cause-specific hazard rate of treatment discontinuation for AEs was similar for TNFi versus JAKi (1.00, 95% CI 0.92 to 1.10) and higher for OMA versus JAKi (1.11, 95% CI 1.01 to 1.23), lower with TNFi compared with tofacitinib (0.81, 95% CI 0.71 to 0.90), but higher for TNFi versus baricitinib (1.15, 95% CI 1.01 to 1.30) and lower for TNFi versus JAKi in patients 65 or older with at least one cardiovascular risk factor (0.79, 95% CI 0.65 to 0.97). CONCLUSION: While JAKi overall were not associated with more treatment discontinuations for AEs, subgroup analyses suggest varying patterns with specific JAKi, such as tofacitinib, compared with TNFi. However, these observations should be interpreted cautiously, given the observational study design.

Authors: R. Aymon, D. Mongin, S. A. Bergstra, D. Choquette, C. Codreanu, D. De Cock, L. Dreyer, O. Elkayam, D. Huschek, K. L. Hyrich, F. Iannone, N. Inanc, L. Kearsley-Fleet, S. S. Koca, T. K. Kvien, B. F. Leeb, G. Lukina, D. C. Nordstrom, K. Pavelka, M. Pombo-Suarez, A. Rodrigues, Z. Rotar, A. Strangfeld, P. Verschueren, R. Westermann, J. Zavada, D. S. Courvoisier, A. Finckh, K. Lauper

Date Published: 2024

Publication Type: Journal

Incidence of Major Adverse Cardiovascular Events in Patients With Rheumatoid Arthritis Treated With JAK Inhibitors Compared With Biologic Disease-Modifying Antirheumatic Drugs: Data From an International Collaboration of Registries

Abstract (Expand)

OBJECTIVE: Our objective was to assess the incidence of major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA) treated with JAK inhibitors (JAKi), tumor necrosis factor … inhibitors (TNFi), or biologic disease-modifying antirheumatic drugs with other modes of action (bDMARD-OMA) in a multicountry, real-world population. METHODS: Patients with RA from 15 registries in the JAK-pot collaboration were included. MACE incidence was analyzed using two approaches: a within-registry analysis aggregating country-specific estimates from registers with >25 incident MACEs through meta-analysis and an individual-level data combined analysis. We used adjusted linear mixed Poisson regression to obtain incidence rate ratios (IRRs) of MACEs between treatment groups, accounting for multiple treatment courses. RESULTS: The study included 73,008 treatment courses (16,417 JAKi, 35,373 TNFi, and 21,218 bDMARD-OMA) and 828 incident MACEs among 51,233 patients. Median follow-up time was 1.3 years, with most of the follow-up concentrated in the first two years of treatment. Incidence rates were 7.0, 7.6, and 11.8 per 1,000 person-years for JAKi, TNFi, and bDMARD-OMA, respectively. Compared to TNFi, JAKi (within-registry adjusted IRR 0.89, 95% confidence interval [CI] 0.63-1.25) had similar incidence rates of MACEs and bDMARD-OMA had higher rates (within-registry adjusted IRR 1.35, 95% CI 1.10-1.66). Combined analysis showed similar results. CONCLUSION: Observational data from the JAK-pot collaboration show no evidence of an increase in cardiovascular events during the first two years of use with JAKi compared to TNFi in the general RA population.

Authors: R. Aymon, D. Mongin, R. Guemara, Z. Salis, J. Askling, D. Choquette, C. Codreanu, D. Di Giuseppe, I. Flouri, D. Huschek, K. L. Hyrich, F. Iannone, T. K. Kvien, B. F. Leeb, D. Nordstrom, L. Otero-Varela, K. Pavelka, M. Pombo-Suarez, A. Rodrigues, Z. Rotar, P. Sidiropoulos, S. A. Provan, A. Strangfeld, T. Nina, J. Zavada, L. Kearsley-Fleet, D. S. Courvoisier, A. Finckh, K. Lauper

Date Published: 2025

Publication Type: Journal

Different risk profiles of biologic agents for new-onset psoriasis in patients with rheumatoid arthritis

Abstract (Expand)

OBJECTIVE: To investigate rates and risk factors for incident and recurrent psoriasis in rheumatoid arthritis (RA) patients treated with different biologic (b) and conventional synthetic (cs) … disease-modifying antirheumatic drugs (DMARDs). METHODS: RA patients enrolled in the German biologics register RABBIT without (n = 14,525) or with a history of psoriasis (n = 375) were analyzed separately. All first events of psoriasis reported until October 2017 were assigned to the treatments prescribed in the previous 3 months. Crude incidence rates (IR) of psoriasis were calculated per 1000 patient-years. To investigate risk factors for psoriasis, cox regressions with and without inverse probability weights were applied to adjust for confounding by indication. RESULTS: 117 incident and 37 recurrent psoriatic events were reported. Patients exposed to TNFi had a significantly higher incidence rate (IR = 3.04/1,000 PY) than those exposed to csDMARDs only (IR = 0.65), whereas IRs for abatacept, rituximab and tocilizumab did not differ significantly from csDMARDs. Adjusted Cox regression confirmed a higher risk for TNFi. Female sex (HR: 1.7) and smoking (HR: 2.1) were significantly associated with incident psoriasis while methotrexate decreased the risk (HR: 0.5). For recurrent psoriasis, IRs for TNFi, abatacept and rituximab were significantly higher than for csDMARDs. CONCLUSIONS: Our data confirm a previously observed increased risk of incident psoriasis in patients exposed to TNFi compared to csDMARDs. However, the overall risk is low and the event is usually non-serious. Comedication of TNFi with methotrexate seems to lower the risk of incident psoriasis. In patients with a history of psoriasis, recurrence as adverse event is rare.

Authors: L. Baganz, J. Listing, J. Kekow, C. Eisterhues, S. Wassenberg, A. Zink, A. Strangfeld

Date Published: 2020

Publication Type: Journal

Are prognostic factors adequately selected to guide treatment decisions in patients with rheumatoid arthritis? A collaborative analysis from three observational cohorts

Abstract (Expand)

OBJECTIVE: To investigate the impact of indicators of unfavorable prognosis ("poor prognostic factors") on the achievement of low disease activity (LDA)/remission in patients with rheumatoid … arthritis (RA). METHODS: Biologic DMARD-naive patients with RA from three observational cohorts were examined. N = 713 patients started their 1st csDMARD, n = 1613 switched to the 2nd csDMARD and n = 388 to the 1st TNF-inhibitor. High disease activity (DAS28 > 5.1), autoantibodies (RF/ACPA positive), prevalent erosions, functional limitation (HAQ >/= 1.2), comorbidities, obesity (BMI > 30 kg/m(2)), and smoking were evaluated as prognostic factors. Generalized regression analyses were applied to investigate prognostic factors regarding the achievement of LDA (DAS28 < 3.2) or remission (DAS28 < 2.6) within six months. RESULTS: At baseline, RF/ACPA positivity was most frequent in all cohorts (60.3-75.3%), followed by DAS28 > 5.1 (35-57.7%), HAQ >/= 1.2 (40.5-52.5%), >/= 2 comorbidities (31.4-54.1%) and erosions (17.1-46.1%). Remission was achieved by 39% (1st-csDMARD), 26% (2nd-csDMARD) and 30% (1st-TNFi). In adjusted regression models DAS28 > 5.1 (OR: 0.41 [0.30;0.56]), HAQ >/= 1.2 (0.56 [0.42;0.74]), current smoking (0.72 [0.53;0.97], obesity (0.66 [0.49;0.89] and >/= 2 comorbidities (0.57 [0.40;0.80]) were independently associated with a lower chance to achieve remission within six months (ORs for 2nd-csDMARD). The proportion of patients in LDA/remission declined by 6-12%-points if DAS28 > 5.1 was present at baseline and by 15-27%-points if functional limitation, comorbidities and obesity were additionally present. In all cohorts RF/ACPA positivity and erosions were not associated with achieving LDA/remission. CONCLUSIONS: While RF/ACPA status and erosions do not affect the achievement of LDA/remission, high disease activity, functional limitation, comorbidities and obesity should be considered as unfavorable prognostic factors in patients starting the 1st or 2nd DMARD strategy.

Authors: L. Baganz, A. Richter, K. Albrecht, M. Schneider, G. R. Burmester, A. Zink, A. Strangfeld

Date Published: 2019

Publication Type: Journal

Long-term effectiveness of tocilizumab in patients with rheumatoid arthritis, stratified by number of previous treatment failures with biologic agents: results from the German RABBIT cohort

Abstract (Expand)

In Germany, Tocilizumab (TCZ) is used for the treatment of rheumatoid arthritis both in biologic-naive patients and those with previous failures of biologic disease-modifying antirheumatic drugs … (bDMARDs). The long-term effectiveness and retention rates of TCZ in patients with different numbers of prior bDMARD failures has rarely been investigated. We included 885 RA patients in the analyses, enrolled with the start of TCZ between 2009 and 2015 in the German biologics register RABBIT. Patients were stratified according to prior bDMARD failures: no prior bDMARD or 1, 2 or >/= 3 bDMARD failures. We applied Kaplan-Meier methods and Cox-regression to examine treatment adherence as well as linear mixed effects models to investigate effectiveness over 3 years of follow-up. Compared to biologic-naive patients, those with prior bDMARD failures at start of TCZ were younger but had significantly longer disease duration and more comorbidities. DAS28 at baseline and loss of physical function were highest in patients with >/= 3 bDMARD failures. During follow-up, patients with up to two bDMARD failures on average reached low disease activity (LDA, DAS28 < 3.2). Those with >/= 3 prior bDMARDs had a slightly lower response. However, after 3 years, nearly 50% of them achieved LDA. Treatment continuation on TCZ therapy was similar in patients with </= 2 bDMARD failures but significantly lower in those with >/= 3 bDMARD failures. TCZ seems to be similarly effective in patients with no, one or two prior bDMARD failures. The majority of patients achieved LDA already after 6 months and maintained it over a period of 3 years. TCZ proved effective even in the high-risk group of patients with more than two prior bDMARD failures.

Authors: L. Baganz, A. Richter, J. Kekow, A. Bussmann, A. Krause, C. Stille, J. Listing, A. Zink, A. Strangfeld

Date Published: 2018

Publication Type: Journal

[Revised version of the statement by the DGRh on biosimilars-update 2017]

Abstract (Expand)

The treatment of rheumatic diseases with bioloics has significantly improved the prognosis of patients. Currently, there are 13 preparations available in Germany for the treatment of patients with … inflammatory rheumatic diseases. These original preparations generally have-depending on the individual country-15 years of patent protection. As soon as the patent has expired, approved biosimilars can be brought into use. For the approval of a biosimilar, authorities such as the European Medical Agency or the American Food and Drug Administration require proof of the best possible comparability with respect to efficacy and safety in comparison to the original or reference product. Since 2015, biosimilars of inifliximab, adalimumab, etanercept and rituximab have been granted approval in the European Union, the USA, Japan and in other countries. Further biosimilar products for these reference products are in development for treatment in rheumatology. From a societal and medical point of view, this opens up the possibility to increase the availability of biopharmaceutical products for patients through lower prices. In Germany, this possibility has already occurred-statutory health insurance physicians have introduced quotas for biosimilars, which will ultimately decrease spending and healthcare costs. This can lead to price reductions of the original products, which has already happened in Germany. Biosimilars can be prescribed for new patients or as a change from the original to the generic drug. When switching, a distinction is made between individual switching (interchangeability), which is made in individual consultation between the physician and the patient, and nonmedical switching (substitution) made at the societal or governmental level, which is made in the context of health care cost containment, and then, for example, implemented at the pharmacy level. Preliminary data from Norway and Denmark are available for substitution on the basis of results from large studies or registries in which systematic changes were made. The previous conclusion was that this does not lead to new problems for the patients. The German Society for Rheumatology recognizes the advantages of introducing biosimilars in Germany, but recommends that their use be based primarily on a joint decision by the treating physician and patient.

Authors: J. Braun, H. M. Lorenz, U. Muller-Ladner, M. Schneider, H. Schulze-Koops, C. Specker, A. Strangfeld, U. Wagner, T. Dorner

Date Published: 2018

Publication Type: Journal

EULAR points to consider when analysing and reporting comparative effectiveness research using observational data in rheumatology

Abstract (Expand)

BACKGROUND: Comparing treatment effectiveness over time in observational settings is hampered by several major threats, among them confounding and attrition bias. OBJECTIVES: To develop European Alliance … of Associations for Rheumatology (EULAR) points to consider (PtC) when analysing and reporting comparative effectiveness research using observational data in rheumatology. METHODS: The PtC were developed using a three-step process according to the EULAR Standard Operating Procedures. Based on a systematic review of methods currently used in comparative effectiveness studies, the PtC were formulated through two in-person meetings of a multidisciplinary task force and a two-round online Delphi, using expert opinion and a simulation study. Finally, feedback from a larger audience was used to refine the PtC. Mean levels of agreement among the task force were calculated. RESULTS: Three overarching principles and 10 PtC were formulated, addressing, in particular, potential biases relating to attrition or confounding by indication. Building on Strengthening the Reporting of Observational Studies in Epidemiology guidelines, these PtC insist on the definition of the baseline for analysis and treatment effectiveness. They also focus on the reasons for stopping treatment as an important consideration when assessing effectiveness. Finally, the PtC recommend providing key information on missingness patterns. CONCLUSION: To improve the reliability of an increasing number of real-world comparative effectiveness studies in rheumatology, special attention is required to reduce potential biases. Adherence to clear recommendations for the analysis and reporting of observational comparative effectiveness studies will improve the trustworthiness of their results.

Authors: D. S. Courvoisier, K. Lauper, J. Kedra, M. de Wit, B. Fautrel, T. Frisell, K. L. Hyrich, F. Iannone, P. M. Machado, L. M. Ornbjerg, Z. Rotar, M. J. Santos, T. A. Stamm, S. R. Stones, A. Strangfeld, S. A. Bergstra, R. B. M. Landewe, A. Finckh

Date Published: 2022

Publication Type: Journal

2018 EULAR recommendations for a core data set to support observational research and clinical care in giant cell arteritis

Abstract (Expand)

Giant cell arteritis (GCA) represents the most common form of primary systemic vasculitis and is frequently associated with comorbidities related to the disease itself or induced by the treatment. … Systematically collected data on disease course, treatment and outcomes of GCA remain scarce. The aim of this EULAR Task Force was to identify a core set of items which can easily be collected by experienced clinicians, in order to facilitate collaborative research into the course and outcomes of GCA. A multidisciplinary EULAR task force group of 20 experts including rheumatologists, internists, epidemiologists and patient representatives was assembled. During a 1-day meeting, breakout groups discussed items from a previously compiled collection of parameters describing GCA status and disease course. Feedback from breakout groups was further discussed. Final consensus was achieved by means of several rounds of email discussions after the meeting. A three-round Delphi survey was conducted to determine a core set of parameters including the level of agreement. 117 parameters were regarded as relevant. Potential items were subdivided into the following categories: General, demographics, GCA-related signs and symptoms, other medical conditions and treatment. Possible instruments and assessment intervals were proposed for documentation of each item. To facilitate implementation of the recommendations in clinical care and clinical research, a minimum core set of 50 parameters was agreed. This proposed core set intends to ensure that relevant items from different GCA registries and databases can be compared for the dual purposes of facilitating clinical research and improving clinical care.

Authors: L. Ehlers, J. Askling, H. W. Bijlsma, M. C. Cid, M. Cutolo, B. Dasgupta, C. Dejaco, W. G. Dixon, N. Feltelius, A. Finckh, K. Gilbert, S. L. Mackie, A. Mahr, E. L. Matteson, L. Neill, C. Salvarani, W. A. Schmidt, A. Strangfeld, R. F. van Vollenhoven, F. Buttgereit

Date Published: 2019

Publication Type: Journal

[Relevant information on reproduction and rheumatism]

Abstract

Not specified

Authors: R. Fischer-Betz, A. Strangfeld, F. Forger

Date Published: 2021

Publication Type: Journal

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

Abstract (Expand)

OBJECTIVES: To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). METHODS: An … international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. RESULTS: Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15-30 mg of prednisolone or equivalent for >2-4 weeks. CONCLUSIONS: These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

Authors: G. E. Fragoulis, E. Nikiphorou, M. Dey, S. S. Zhao, D. S. Courvoisier, L. Arnaud, F. Atzeni, G. M. Behrens, J. W. Bijlsma, P. Bohm, C. A. Constantinou, S. Garcia-Diaz, M. C. Kapetanovic, K. Lauper, M. Luis, J. Morel, G. Nagy, E. Polverino, J. van Rompay, M. Sebastiani, A. Strangfeld, A. de Thurah, J. Galloway, K. L. Hyrich

Date Published: 2023

Publication Type: Journal

[The importance of patient perspective in drug surveillance systems]

Abstract (Expand)

AIMS: using data from the German biologics register RABBIT we investigated which gain in information can be achieved by integrating patient-reported adverse drug reactions (ADRs) into drug surveillance … systems. METHODS: patients with rheumatoid arthritis enrolled in the longitudinal cohort of the German biologics register between May 2001 and September 2006 who had undergone at least one follow-up were included in the study. All ADRs reported to the register either by the treating rheumatologists or the patients were coded with the same coding system (MedDRA(R)). The agreement between patients and physicians was analysed for the most frequently reported ADRs using the patient as gold standard. RESULTS: data from 4246 patients with a mean observation time of 2 years were analysed. Patients reported on average 1.2 ADRs per patient year (PY), while physicians indicated 1 ADR per PY (p<0,001). The ADR most frequently reported by patients was nausea (93.8 per 1000 PY), followed by fatigue (72.5 per 1000 PYs) and alopecia (60.6 per 1000 PYs). These ADRs were significantly less often reported by physicians. Agreement between patients and physicians was higher in more objective symptoms, such as injection site reaction (in 60.0% of cases where the patient reported this symptom, the physician did so too) or rash (53.0%), than in more subjective symptoms such as fatigue (17.4%). Agreement was highest in life-threatening events. CONCLUSIONS: patients report a higher number of ADRs than their treating physicians. Patients report subjective symptoms impacting on quality of life more frequently than physicians. Patient-physician agreement on known or clinically relevant ARDs is high. Integration of patient reports on ADRs into clinical routine could enhance the patient-physician partnership and improve compliance as well as awareness of signs and symptoms of possible ADRs.

Authors: L. Gawert, F. Hierse, A. Zink, A. Strangfeld

Date Published: 2010

Publication Type: Journal

How well do patient reports reflect adverse drug reactions reported by rheumatologists? Agreement of physician- and patient-reported adverse events in patients with rheumatoid arthritis observed in the German biologics register

Abstract (Expand)

OBJECTIVE: To analyse the validity of patient reports on adverse drug reactions (ADRs) compared with the reports given by the treating physician. METHODS: Patients with RA enrolled in the German biologics … register rheumatoid arthritis observation of biologic therapy (RABBIT) between May 2001 and September 2006 were included in the study. We investigated concordance of reporting and level of agreement between physician- and patient-reported ADRs, taking the physician as gold standard. RESULTS: Data from 4246 patients were analysed. Patients reported on average 1.2 ADRs per patient-year (PY) compared with 0.8 ADRs reported by the physicians (P<0.001). Gastrointestinal disorders were the most frequently reported ADRs by patients (277.8/1000 PYs) and physicians (137.8/1000 PYs), infections were reported with considerably higher frequency by physicians (124/1000 PYs) than by patients (72/1000 PYs). Agreement between patients and physicians (same or similar event reported at the same time) differed according to the nature of the reported ADR. High agreement was found for easily observable, known ADRs (such as alopecia, agreement 76.7%) In contrast, even for some serious ADRs, many patients did not see a connection between the event and the drug taken (e.g. pneumonia, agreement 37.7%). CONCLUSIONS: Patient reports on ADRs are a useful source of information on the safety of new therapies. However, drug surveillance cannot rely on patient reports only, since even life-threatening events were not reported as ADRs by the patients who failed to associate them with the therapy. When coding patient reports on ADRs to a standard coding system, the differences in language and terminology between patients and physicians should be taken into account.

Authors: L. Gawert, F. Hierse, A. Zink, A. Strangfeld

Date Published: 2011

Publication Type: Journal

Health-related quality of life in patients with long-standing rheumatoid arthritis in the era of biologics: data from the German biologics register RABBIT

Abstract (Expand)

OBJECTIVE: To compare the 24-month course of health-related quality of life (HRQoL) in patients with long-standing RA treated with a conventional synthetic (cs) or a first, second or third biologic (b) … DMARD in daily rheumatological care. METHODS: Patients enrolled in the German biologics register RABBIT who were observed over at least 12 months were stratified according to the nth bDMARD started at enrolment. HRQoL was captured by the SF36 health survey. Within strata of sequential bDMARD therapy, we examined patients’ HRQoL at baseline and at follow-ups in comparison with the general population, the 24-month course of HRQoL of different bDMARDs and the proportion of patients exceeding the minimal detectable improvement of physical and mental health sum scores. RESULTS: All patients reported remarkably lower scores of physical and mental health than the general population at baseline and month 12. In each stratum of sequential bDMARD therapy, patients improved significantly by month 12 and remained stable until month 24. The improvement of HRQoL was not attributable to a particular bDMARD. The following proportions of patients exceeded the minimal detectable improvement of at least 17.85 Physical Component Scale scores or 22.18 Mental Component Scale score points: csDMARD (n = 1113) 31.1%/22.3%, first bDMARD (n = 1352) 39.9%/29.7%, second bDMARD (n = 730) 37.3%/26.2% and third bDMARD (n = 680) 34.2%/30.9%. CONCLUSION: Lasting improvement of both physical and mental health is achievable even for severely affected RA patients with a history of more than one bDMARD failure. Nevertheless, impairment of HRQoL in RA patients is enormous compared with the general population.

Authors: K. Gerhold, A. Richter, M. Schneider, H. J. Bergerhausen, W. Demary, A. Liebhaber, J. Listing, A. Zink, A. Strangfeld

Date Published: 2015

Publication Type: Journal

Older age, comorbidity, glucocorticoid use and disease activity are risk factors for COVID-19 hospitalisation in patients with inflammatory rheumatic and musculoskeletal diseases

Abstract (Expand)

INTRODUCTION: Whether patients with inflammatory rheumatic and musculoskeletal diseases (RMD) are at higher risk to develop severe courses of COVID-19 has not been fully elucidated. Aim of this analysis … was to describe patients with RMD according to their COVID-19 severity and to identify risk factors for hospitalisation. METHODS: Patients with RMD with PCR confirmed SARS-CoV-2 infection reported to the German COVID-19 registry from 30 March to 1 November 2020 were evaluated. Multivariable logistic regression was used to estimate ORs for hospitalisation due to COVID-19. RESULTS: Data from 468 patients with RMD with SARS-CoV-2 infection were reported. Most frequent diagnosis was rheumatoid arthritis, RA (48%). 29% of the patients were hospitalised, 5.5% needed ventilation. 19 patients died. Multivariable analysis showed that age >65 years (OR 2.24; 95% CI 1.12 to 4.47), but even more>75 years (OR 3.94; 95% CI 1.86 to 8.32), cardiovascular disease (CVD; OR 3.36; 95% CI 1.5 to 7.55), interstitial lung disease/chronic obstructive pulmonary disease (ILD/COPD) (OR 2.79; 95% CI 1.2 to 6.49), chronic kidney disease (OR 2.96; 95% CI 1.16 to 7.5), moderate/high RMD disease activity (OR 1.96; 95% CI 1.02 to 3.76) and treatment with glucocorticoids (GCs) in dosages >5 mg/day (OR 3.67; 95% CI 1.49 to 9.05) were associated with higher odds of hospitalisation. Spondyloarthritis patients showed a smaller risk of hospitalisation compared with RA (OR 0.46; 95% CI 0.23 to 0.91). CONCLUSION: Age was a major risk factor for hospitalisation as well as comorbidities such as CVD, ILD/COPD, chronic kidney disease and current or prior treatment with GCs. Moderate to high RMD disease activity was also an independent risk factor for hospitalisation, underlining the importance of continuing adequate RMD treatment during the pandemic.

Authors: R. Hasseli, U. Mueller-Ladner, B. F. Hoyer, A. Krause, H. M. Lorenz, A. Pfeil, J. Richter, M. Schafer, T. Schmeiser, A. Strangfeld, H. Schulze-Koops, R. E. Voll, C. Specker, A. C. Regierer

Date Published: 2021

Publication Type: Journal

National registry for patients with inflammatory rheumatic diseases (IRD) infected with SARS-CoV-2 in Germany (ReCoVery): a valuable mean to gain rapid and reliable knowledge of the clinical course of SARS-CoV-2 infections in patients with IRD

Abstract (Expand)

OBJECTIVES: Patients with inflammatory rheumatic diseases (IRD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be at risk to develop a severe course of COVID-19. The … influence of immunomodulating drugs on the course of COVID-19 is unknown. To gather knowledge about SARS-CoV-2 infections in patients with IRD, we established a registry shortly after the beginning of the pandemic in Germany. METHODS: Using an online questionnaire (www.COVID19-rheuma.de), a nationwide database was launched on 30 March 2020, with appropriate ethical and data protection approval to collect data of patients with IRD infected with SARS-CoV-2. In this registry, key clinical and epidemiological parameters-for example, diagnosis of IRD, antirheumatic therapies, comorbidities and course of the infection-are documented. RESULTS: Until 25 April 2020, data from 104 patients with IRD infected with SARS-CoV-2 were reported (40 males; 63 females; 1 diverse). Most of them (45%) were diagnosed with rheumatoid arthritis, 59% had one or more comorbidities and 42% were treated with biological disease-modifying antirheumatic drugs. Hospitalisation was reported in 32% of the patients. Two-thirds of the patients already recovered. Unfortunately, 6 patients had a fatal course. CONCLUSIONS: In a short time, a national registry for SARS-CoV2-infected patients with IRD was established. Within 4 weeks, 104 cases were documented. The registry enables to generate data rapidly in this emerging situation and to gain a better understanding of the course of SARS-CoV2-infection in patients with IRD, with a distinct focus on their immunomodulatory therapies. This knowledge is valuable for timely information of physicians and patients with IRD, and shall also serve for the development of guidance for the management of patients with IRD during this pandemic.

Authors: R. Hasseli, U. Mueller-Ladner, T. Schmeiser, B. F. Hoyer, A. Krause, H. M. Lorenz, A. C. Regierer, J. G. Richter, A. Strangfeld, R. E. Voll, A. Pfeil, H. Schulze-Koops, C. Specker

Date Published: 2020

Publication Type: Journal

[German registry www.Covid19-Rheuma.de : Status report after 1 year of the pandemic]

Abstract (Expand)

The COVID-19 registry ( www.covid19-rheuma.de ) of the German Society of Rheumatology was the first registry for the acquisition and systemic evaluation of viral infections in patients with inflammatory … rheumatic diseases (IRD). This has enabled rapid generation of scientific data that will help to improve the care of patients with IRD in the context of the pandemic. In addition to confirming general risk factors, such as patient age and comorbidities (e.g. cardiovascular, chronic lung and kidney diseases), the use of glucocorticoids and the disease activity of the rheumatic disease could be identified as disease-specific independent risk factors for the need of hospitalization due to COVID-19. Evaluations of the continuously growing cohort of patients with IRD and COVID-19 enable recommendations for patient care to be based on better evidence. Cooperation with international rheumatology registries (e.g. European COVID-19 registry for IRD) enables analyses of aggregated cohorts of patients with IRD and COVID-19 for international comparisons and statistically even more reliable statements.

Authors: R. Hasseli, A. Pfeil, B. F. Hoyer, H. M. Lorenz, A. C. Regierer, J. G. Richter, T. Schmeiser, A. Strangfeld, R. E. Voll, A. Krause, H. Schulze-Koops, U. Muller-Ladner, C. Specker

Date Published: 2021

Publication Type: Journal

A survey to evaluate knowledge, perceptions and attitudes toward COVID-19 vaccinations among rheumatologists in Germany

Abstract (Expand)

The objective is to evaluate the attitude of rheumatologists regarding the use of COVID-19 vaccination in patients with inflammatory rheumatic diseases (IRDs). From February 2nd until March 15th, 2021, … rheumatologists from Germany were asked to participate anonymously in a survey addressing their attitude with respect to COVID-19 vaccinations of IRD patients. The survey was completed by 214 participants (107 men, 103 women, 4 unspecified). More than half of the physicians (61%) were working in rheumatologic private practices and 62% had more than 20 years of experience in rheumatology. 90% reported to be at least confidential in handling issues of COVID-19 vaccination and 99% would recommend COVID-19 vaccination for IRD patients. The majority would not recommend to stop or reduce immunomodulatory drugs for vaccination except for rituximab. More than 70% would prefer vaccination with a mRNA vaccine for their IRD patients. This study shows that almost all rheumatologists in Germany support the COVID-19 vaccination for their IRD patients without reducing or terminating the actual immunomodulatory medication to potentially improve the response to the vaccine. This attitude is in accordance with the current recommendations of the German Society of Rheumatology regarding COVID-19 vaccination in IRD patients, and indicates that these have been well accepted and work in everyday clinical practice.

Authors: R. Hasseli, A. Pfeil, A. Krause, H. Schulze-Koops, U. Muller-Ladner, C. Specker, Covid- Task Force of the German Society for Rheumatology

Date Published: 2021

Publication Type: Journal

Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19

Abstract (Expand)

IMPORTANCE: Although tumor necrosis factor (TNF) inhibitors are widely prescribed globally because of their ability to ameliorate shared immune pathways across immune-mediated inflammatory diseases … (IMIDs), the impact of COVID-19 among individuals with IMIDs who are receiving TNF inhibitors remains insufficiently understood. OBJECTIVE: To examine the association between the receipt of TNF inhibitor monotherapy and the risk of COVID-19-associated hospitalization or death compared with other commonly prescribed immunomodulatory treatment regimens among adult patients with IMIDs. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a pooled analysis of data from 3 international COVID-19 registries comprising individuals with rheumatic diseases, inflammatory bowel disease, and psoriasis from March 12, 2020, to February 1, 2021. Clinicians directly reported COVID-19 outcomes as well as demographic and clinical characteristics of individuals with IMIDs and confirmed or suspected COVID-19 using online data entry portals. Adults (age >/=18 years) with a diagnosis of inflammatory arthritis, inflammatory bowel disease, or psoriasis were included. EXPOSURES: Treatment exposure categories included TNF inhibitor monotherapy (reference treatment), TNF inhibitors in combination with methotrexate therapy, TNF inhibitors in combination with azathioprine/6-mercaptopurine therapy, methotrexate monotherapy, azathioprine/6-mercaptopurine monotherapy, and Janus kinase (Jak) inhibitor monotherapy. MAIN OUTCOMES AND MEASURES: The main outcome was COVID-19-associated hospitalization or death. Registry-level analyses and a pooled analysis of data across the 3 registries were conducted using multilevel multivariable logistic regression models, adjusting for demographic and clinical characteristics and accounting for country, calendar month, and registry-level correlations. RESULTS: A total of 6077 patients from 74 countries were included in the analyses; of those, 3215 individuals (52.9%) were from Europe, 3563 individuals (58.6%) were female, and the mean (SD) age was 48.8 (16.5) years. The most common IMID diagnoses were rheumatoid arthritis (2146 patients [35.3%]) and Crohn disease (1537 patients [25.3%]). A total of 1297 patients (21.3%) were hospitalized, and 189 patients (3.1%) died. In the pooled analysis, compared with patients who received TNF inhibitor monotherapy, higher odds of hospitalization or death were observed among those who received a TNF inhibitor in combination with azathioprine/6-mercaptopurine therapy (odds ratio [OR], 1.74; 95% CI, 1.17-2.58; P = .006), azathioprine/6-mercaptopurine monotherapy (OR, 1.84; 95% CI, 1.30-2.61; P = .001), methotrexate monotherapy (OR, 2.00; 95% CI, 1.57-2.56; P < .001), and Jak inhibitor monotherapy (OR, 1.82; 95% CI, 1.21-2.73; P = .004) but not among those who received a TNF inhibitor in combination with methotrexate therapy (OR, 1.18; 95% CI, 0.85-1.63; P = .33). Similar findings were obtained in analyses that accounted for potential reporting bias and sensitivity analyses that excluded patients with a COVID-19 diagnosis based on symptoms alone. CONCLUSIONS AND RELEVANCE: In this cohort study, TNF inhibitor monotherapy was associated with a lower risk of adverse COVID-19 outcomes compared with other commonly prescribed immunomodulatory treatment regimens among individuals with IMIDs.

Editor:

Date Published: 2021

Publication Type: Journal

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study

Abstract (Expand)

BACKGROUND: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate … the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. METHODS: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. FINDINGS: 14 044 patients from 23 countries were included in the analyses. 10 178 (72.5%) individuals were female and 3866 (27.5%) were male, with a mean age of 54.4 years (SD 15.6). Air pollution (odds ratio 1.10 per 10 mug/m(3) [95% CI 1.01-1.17]; p=0.0105), proportion of the population aged 65 years or older (1.19 per 1% increase [1.10-1.30]; p<0.0001), and population mobility (1.03 per 1% increase in number of visits to grocery and pharmacy stores [1.02-1.05]; p<0.0001 and 1.02 per 1% increase in number of visits to workplaces [1.00-1.03]; p=0.032) were independently associated with higher odds of mortality. Number of hospital beds (0.94 per 1-unit increase per 1000 people [0.88-1.00]; p=0.046), human development index (0.65 per 0.1-unit increase [0.44-0.96]; p=0.032), government response stringency (0.83 per 10-unit increase in containment index [0.74-0.93]; p=0.0018), as well as follow-up time (0.78 per month [0.69-0.88]; p<0.0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1.2% [0.1-9.5]; p=0.14). INTERPRETATION: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities. FUNDING: American College of Rheumatology and European Alliance of Associations for Rheumatology.

Authors: Z. Izadi, M. A. Gianfrancesco, G. Schmajuk, L. Jacobsohn, P. Katz, S. Rush, C. Ja, T. Taylor, K. Shidara, M. I. Danila, K. D. Wysham, A. Strangfeld, E. F. Mateus, K. L. Hyrich, L. Gossec, L. Carmona, S. Lawson-Tovey, L. Kearsley-Fleet, M. Schaefer, S. Al-Emadi, J. A. Sparks, T. Y. Hsu, N. J. Patel, L. Wise, E. Gilbert, A. Duarte-Garcia, M. O. Valenzuela-Almada, M. F. Ugarte-Gil, L. Ljung, C. A. Scire, G. Carrara, E. Hachulla, C. Richez, P. Cacoub, T. Thomas, M. J. Santos, M. Bernardes, R. Hasseli, A. Regierer, H. Schulze-Koops, U. Muller-Ladner, G. Pons-Estel, R. Tanten, R. E. Nieto, C. N. Pisoni, Y. S. Tissera, R. Xavier, C. D. Lopes Marques, G. C. S. Pileggi, P. C. Robinson, P. M. Machado, E. Sirotich, J. W. Liew, J. S. Hausmann, P. Sufka, R. Grainger, S. Bhana, M. Gore-Massy, Z. S. Wallace, J. Yazdany, Covid- Global Rheumatology Alliance Registry

Date Published: 2022

Publication Type: Journal

Consensus-based recommendations for the use of biosimilars to treat rheumatological diseases

Abstract (Expand)

The study aimed to develop evidence-based recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases. The task force comprised an expert group of specialists in … rheumatology, dermatology and gastroenterology, and pharmacologists, patients and a regulator from ten countries. Four key topics regarding biosimilars were identified through a process of discussion and consensus. Using a Delphi process, specific questions were then formulated to guide a systematic literature review. Relevant English-language publications through November 2016 were searched systematically for each topic using Medline; selected papers and pertinent reviews were examined for additional relevant references; and abstracts presented at the 2015 and 2016 American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) annual scientific meetings were searched for those about biosimilars. The experts used evidence obtained from these studies to develop a set of overarching principles and consensus recommendations. The level of evidence and grade of recommendation were determined for each. By the search strategy, 490 references were identified. Of these, 29 full-text papers were included in the systematic review. Additionally, 20 abstracts were retrieved from the ACR and EULAR conference abstract databases. Five overarching principles and eight consensus recommendations were generated, encompassing considerations regarding clinical trials, immunogenicity, extrapolation of indications, switching between bio-originators and biosimilars and among biosimilars, and cost. The level of evidence and grade of recommendation for each varied according to available published evidence. Five overarching principles and eight consensus recommendations regarding the evaluation and use of biosimilars to treat rheumatological diseases were developed using research-based evidence and expert opinion.

Authors: J. Kay, M. M. Schoels, T. Dorner, P. Emery, T. K. Kvien, J. S. Smolen, F. C. Breedveld, Diseases Task Force on the Use of Biosimilars to Treat Rheumatological

Date Published: 2018

Publication Type: Journal

Outcomes of SARS-CoV-2 infection among children and young people with pre-existing rheumatic and musculoskeletal diseases

Abstract (Expand)

OBJECTIVES: Some adults with rheumatic and musculoskeletal diseases (RMDs) are at increased risk of COVID-19-related death. Excluding post-COVID-19 multisystem inflammatory syndrome of children, children … and young people (CYP) are overall less prone to severe COVID-19 and most experience a mild or asymptomatic course. However, it is unknown if CYP with RMDs are more likely to have more severe COVID-19. This analysis aims to describe outcomes among CYP with underlying RMDs with COVID-19. METHODS: Using the European Alliance of Associations for Rheumatology COVID-19 Registry, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Registry, and the CARRA-sponsored COVID-19 Global Paediatric Rheumatology Database, we obtained data on CYP with RMDs who reported SARS-CoV-2 infection (presumptive or confirmed). Patient characteristics and illness severity were described, and factors associated with COVID-19 hospitalisation were investigated. RESULTS: 607 CYP with RMDs <19 years old from 25 different countries with SARS-CoV-2 infection were included, the majority with juvenile idiopathic arthritis (JIA; n=378; 62%). Forty-three (7%) patients were hospitalised; three of these patients died. Compared with JIA, diagnosis of systemic lupus erythematosus, mixed connective tissue disease, vasculitis, or other RMD (OR 4.3; 95% CI 1.7 to 11) or autoinflammatory syndrome (OR 3.0; 95% CI 1.1 to 8.6) was associated with hospitalisation, as was obesity (OR 4.0; 95% CI 1.3 to 12). CONCLUSIONS: This is the most significant investigation to date of COVID-19 in CYP with RMDs. It is important to note that the majority of CYP were not hospitalised, although those with severe systemic RMDs and obesity were more likely to be hospitalised.

Authors: L. Kearsley-Fleet, M. L. Chang, S. Lawson-Tovey, R. Costello, S. Fingerhutova, N. Svestkova, A. Belot, F. A. Aeschlimann, I. Melki, I. Kone-Paut, S. Eulert, T. Kallinich, Y. Berkun, Y. Uziel, B. Raffeiner, F. Oliveira Ramos, D. Clemente, C. Dackhammar, N. M. Wulffraat, H. Waite, A. Strangfeld, E. F. Mateus, P. M. Machado, Carra Registry Investigators, Covid- Global Pediatric Rheumatology Database Investigators, M. Natter, K. L. Hyrich

Date Published: 2022

Publication Type: Journal

Incidence and prevalence of juvenile chronic arthritis in East Berlin 1980-88

Abstract (Expand)

OBJECTIVE: To estimate the incidence and prevalence rates of juvenile chronic arthritis (JCA). METHODS: The study population was children under 16 years of age living in the East Berlin area (part of … the former German Democratic Republic). By admission order that was effective up to 1990, all children with symptoms of a rheumatic disease living in the East Berlin area had to be referred to the 2nd Children’s Hospital at Berlin-Buch. This specific condition allowed us to ascertain cases from the clinical records and to calculate population rates. Based upon this data, the results of surveys with different methods of case ascertainment are compared. RESULTS: An incidence rate of 3.5 per 100,000 and a prevalence rate of 2.0 per 10,000 children were calculated. The frequency of JCA is higher for girls, with an incidence of 4.3 per 100,000 and a prevalence of 2.3 per 10,000. The figures for boys are 2.7 per 100,000 and 1.7 per 10,000, respectively. CONCLUSION: Because of the specific prerequisites, the population rates of prevalence and incidence that were based on clinical records can be regarded as valid in this study. Deviant results of other surveys can be explained by differences in the study design or in the diagnostic procedures used.

Authors: U. Kiessling, E. Doring, J. Listing, J. Meincke, M. Schontube, A. Strangfeld, A. Zink

Date Published: 1998

Publication Type: Journal

Multiple morbidities are associated with serious infections in patients with rheumatoid arthritis

Abstract (Expand)

OBJECTIVE: To assess the association between a comprehensive list of morbidities and serious infection (SI) in patients with rheumatoid arthritis (RA). METHODS: This study evaluated SI risk associated … with 55 comorbidities using a population-based inception cohort including all adult patients with incident RA from 1999 through 2014 with follow up through 2021. Morbidities and SI were ascertained using previously validated international classification of disease (ICD)-9 and ICD-10 codes. Conditional frailty models were utilized to analyze the association between each morbidity and SI: Model 1 adjusted for age, sex, and calendar year; Model 2 adjusted for factors in Model 1 and the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score of Infections; and Model 3 adjusted for factors in Model 1 and the Mayo SI Risk Score. RESULTS: 911 patients (70 % female, mean age 56 years, 66 % seropositive) were included. There were 293 SI among 155 patients (17 %), corresponding to an incidence of 3.9 SI per 100 person-years. Eighteen SI were fatal. Risk of SI was significantly increased in 27 of 55 morbidities in Model 1, 11 morbidities in Model 2, and 23 morbidities in Model 3. Additionally, several morbidities included in the RABBIT and Mayo risk scores continued to have large effect sizes despite adjustment. Serious infection risk increased by 11-16 % per morbidity in the three models. CONCLUSIONS: Several morbidities are associated with an increased risk for SI. Future risk scores may include morbidities identified in this study for improved SI risk assessment.

Authors: B. A. Kimbrough, C. S. Crowson, R. J. Lennon, J. M. Davis, A. Strangfeld, E. Myasoedova

Date Published: 2024

Publication Type: Journal

[Does methotrexate influence the efficacy of vaccination against SARS-CoV-2?]

Abstract (Expand)

The question whether an ongoing treatment with methotrexate (MTX) actually impairs the protective immune response after SARS-CoV‑2 vaccination cannot be answered with certainty on the basis of the … available data. However, in view of the fact that a short discontinuation (once or twice) of the weekly MTX treatment in patients with a stable disease situation is probably associated with a comparatively low risk of inducing a flare of the underlying inflammatory rheumatic disease, such a short discontinuation of treatment can be considered according to the individual decision involving the patient and the treating rheumatologist. Nevertheless, discontinuation of MTX treatment does not appear to be absolutely necessary-especially since discontinuation would have to occur twice within a short period of time for most COVID-19 vaccines. Under no circumstances should longer periods of discontinuation of treatment be considered as this could result in a flare of the underlying disease. A more detailed assessment of the data situation and the resulting consequences (also with respect to DMARD) will follow soon in the updated recommendations for action of the German Society for Rheumatology (DGRh) on the management of patients with inflammatory rheumatic diseases in the context of the SARS-CoV‑2 pandemic, especially COVID-19.

Editor:

Date Published: 2021

Publication Type: Journal

Effectiveness of TNF-inhibitors, abatacept, IL6-inhibitors and JAK-inhibitors in 31 846 patients with rheumatoid arthritis in 19 registers from the ’JAK-pot’ collaboration

Abstract (Expand)

BACKGROUND: JAK-inhibitors (JAKi), recently approved in rheumatoid arthritis (RA), have changed the landscape of treatment choices. We aimed to compare the effectiveness of four current second-line … therapies of RA with different modes of action, since JAKi approval, in an international collaboration of 19 registers. METHODS: In this observational cohort study, patients initiating tumour necrosis factor inhibitors (TNFi), interleukin-6 inhibitors (IL-6i), abatacept (ABA) or JAKi were included. We compared the effectiveness of these treatments in terms of drug discontinuation and Clinical Disease Activity Index (CDAI) response rates at 1 year. Analyses were adjusted for patient, disease and treatment characteristics, including lines of therapy and accounted for competing risk. RESULTS: We included 31 846 treatment courses: 17 522 TNFi, 2775 ABA, 3863 IL-6i and 7686 JAKi. Adjusted analyses of overall discontinuation were similar across all treatments. The main single reason of stopping treatment was ineffectiveness. Compared with TNFi, JAKi were less often discontinued for ineffectiveness (adjusted HR (aHR) 0.75, 95% CI 0.67 to 0.83), as was IL-6i (aHR 0.76, 95% CI 0.67 to 0.85) and more often for adverse events (aHR 1.16, 95% CI 1.03 to 1.33). Adjusted CDAI response rates at 1 year were similar between TNFi, JAKi and IL-6i and slightly lower for ABA. CONCLUSION: The adjusted overall drug discontinuation and 1 year response rates of JAKi and IL-6i were similar to those observed with TNFi. Compared with TNFi, JAKi were more often discontinued for adverse events and less for ineffectiveness, as were IL-6i.

Authors: K. Lauper, M. Iudici, D. Mongin, S. A. Bergstra, D. Choquette, C. Codreanu, R. Cordtz, D. De Cock, L. Dreyer, O. Elkayam, E. M. Hauge, D. Huschek, K. L. Hyrich, F. Iannone, N. Inanc, L. Kearsley-Fleet, E. K. Kristianslund, T. K. Kvien, B. F. Leeb, G. Lukina, D. C. Nordstrom, K. Pavelka, M. Pombo-Suarez, Z. Rotar, M. J. Santos, A. Strangfeld, P. Verschueren, D. S. Courvoisier, A. Finckh

Date Published: 2022

Publication Type: Journal

Analysing and reporting of observational data: a systematic review informing the EULAR points to consider when analysing and reporting comparative effectiveness research with observational data in rheumatology

Abstract (Expand)

OBJECTIVES: To evaluate the analysis and reporting of comparative effectiveness research with observational data in rheumatology, informing European Alliance of Associations for Rheumatology points to … consider. METHODS: We performed a systematic literature review searching Ovid MEDLINE for original articles comparing drug effectiveness in longitudinal observational studies, published in key rheumatology journals between 2008 and 2019. The extracted information focused on reporting and types of analyses. We evaluated if year of publication impacted results. RESULTS: From 9969 abstracts reviewed, 211 articles fulfilled the inclusion criteria. Ten per cent of studies did not adjust for confounding factors. Some studies did not explain how they chose covariates for adjustment (9%), used bivariate screening (21%) and/or stepwise selection procedures (18%). Only 33% studies reported the number of patients lost to follow-up and 25% acknowledged attrition (drop-out or treatment cessation). To account for attrition, studies used non-responder imputation, followed by last observation carried forward (LOCF) and complete case (CC) analyses. Most studies did not report the number of missing data on covariates (83%), and when addressed, 49% used CC and 11% LOCF. Date of publication did not influence the results. CONCLUSION: Most studies did not acknowledge missing data and attrition, and a tenth did not adjust for any confounding factors. When attempting to account for them, several studies used methods which potentially increase bias (LOCF, CC analysis, bivariate screening...). This study shows that there is no improvement over the last decade, highlighting the need for recommendations for the assessment and reporting of comparative drug effectiveness in observational data in rheumatology.

Authors: K. Lauper, J. Kedra, M. de Wit, B. Fautrel, T. Frisell, K. L. Hyrich, F. Iannone, P. M. Machado, L. M. Ornbjerg, Z. Rotar, M. J. Santos, T. A. Stamm, S. R. Stones, A. Strangfeld, R. B. Landewe, A. Finckh, S. A. Bergstra, D. S. Courvoisier

Date Published: 2021

Publication Type: Journal

SARS-CoV-2 infection after vaccination in patients with inflammatory rheumatic and musculoskeletal diseases

Abstract

Not specified

Authors: S. Lawson-Tovey, K. L. Hyrich, L. Gossec, A. Strangfeld, L. Carmona, B. Raffeiner, G. K. Yardimci, L. Trefond, N. Roux, A. Rodrigues, C. Papagoras, E. F. Mateus, X. Mariette, P. M. Machado

Date Published: 2022

Publication Type: Journal

SARS-CoV-2 vaccine safety in adolescents with inflammatory rheumatic and musculoskeletal diseases and adults with juvenile idiopathic arthritis: data from the EULAR COVAX physician-reported registry

Abstract (Expand)

BACKGROUND: There is a lack of data on SARS-CoV-2 vaccination safety in children and young people (CYP) with rheumatic and musculoskeletal diseases (RMDs). Current vaccination guidance is based on data … from adults with RMDs or CYP without RMDs. OBJECTIVES: To describe the safety of SARS-COV-2 vaccination in adolescents with inflammatory RMDs and adults with juvenile idiopathic arthritis (JIA). METHODS: We described patient characteristics, flares and adverse events (AEs) in adolescent cases under 18 with inflammatory RMDs and adult cases aged 18 or above with JIA submitted to the European Alliance of Associations for Rheumatology COVAX registry. RESULTS: A total of 110 cases were reported to the registry. Thirty-six adolescent cases were reported from four countries, most with JIA (42%). Over half (56%) reported early reactogenic-like AEs. One mild polyarthralgia flare and one serious AE of special interest (malaise) were reported. No CYP reported SARS-CoV-2 infection postvaccination.Seventy-four adult JIA cases were reported from 11 countries. Almost two-thirds (62%) reported early reactogenic-like AEs and two flares were reported (mild polyarthralgia and moderate uveitis). No serious AEs of special interest were reported among adults with JIA. Three female patients aged 20-30 years were diagnosed with SARS-CoV-2 postvaccination; all fully recovered. CONCLUSIONS: This is an important contribution to research on SARS-CoV-2 vaccine safety in adolescents with RMDs and adults with JIA. It is important to note the low frequency of disease flares, serious AEs and SARS-CoV-2 reinfection seen in both populations, although the dataset is limited by its size.

Authors: S. Lawson-Tovey, P. M. Machado, A. Strangfeld, E. Mateus, L. Gossec, L. Carmona, B. Raffeiner, I. Bulina, D. Clemente, J. Zepa, A. M. Rodrigues, X. Mariette, K. L. Hyrich, Covax Eular

Date Published: 2022

Publication Type: Journal

EULAR COVID-19 registry: lessons learnt and future considerations

Abstract

Not specified

Authors: S. Lawson-Tovey, A. Strangfeld, K. L. Hyrich, L. Carmona, D. Rodrigues, L. Gossec, E. F. Mateus, P. M. Machado

Date Published: 2021

Publication Type: Journal

Implementing an automated monitoring process in a digital, longitudinal observational cohort study

Abstract (Expand)

BACKGROUND: Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort … concentrates on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research. METHODS: An automated digital monitoring system for cohort studies developed by the German Rheumatism Research Centre (DRFZ) was tested within the disease register RABBIT-SpA, a longitudinal observational study including patients with axial spondyloarthritis and psoriatic arthritis. Physicians and patients complete electronic case report forms (eCRF) twice a year for up to 10 years. Automatic plausibility checks were implemented to verify all data after entry into the eCRF. To identify conflicts that cannot be found by this approach, all possible conflicts were compiled into a catalog. This "conflict catalog" was used to create queries, which are displayed as part of the eCRF. The proportion of queried eCRFs and responses were analyzed by descriptive methods. For the analysis of responses, the type of conflict was assigned to either a single conflict only (affecting individual items) or a conflict that required the entire eCRF to be queried. RESULTS: Data from 1883 patients was analyzed. A total of n = 3145 eCRFs submitted between baseline (T0) and T3 (12 months) had conflicts (40-64%). Fifty-six to 100% of the queries regarding eCRFs that were completely missing were answered. A mean of 1.4 to 2.4 single conflicts occurred per eCRF, of which 59-69% were answered. The most common missing values were CRP, ESR, Schober’s test, data on systemic glucocorticoid therapy, and presence of enthesitis. CONCLUSION: Providing high data quality in large observational cohort studies is a major challenge, which requires careful monitoring. An automated monitoring process was successfully implemented and well accepted by the study centers. Two thirds of the queries were answered with new data. While conventional manual monitoring is resource-intensive and may itself create new sources of errors, automated processes are a convenient way to augment data quality.

Authors: L. Lindner, A. Weiss, A. Reich, S. Kindler, F. Behrens, J. Braun, J. Listing, G. Schett, J. Sieper, A. Strangfeld, A. C. Regierer

Date Published: 2021

Publication Type: Journal

Mortality in rheumatoid arthritis: the impact of disease activity, treatment with glucocorticoids, TNFalpha inhibitors and rituximab

Abstract (Expand)

OBJECTIVES: To investigate the impact of disease activity, the course of the disease, its treatment over time, comorbidities and traditional risk factors on survival. METHODS: Data of the German biologics … register RABBIT were used. Cox regression was applied to investigate the impact of time-varying covariates (disease activity as measured by the DAS28, functional capacity, treatment with glucocorticoids, biologic or synthetic disease modifying antirheumatic drugs (DMARDs)) on mortality after adjustment for age, sex, comorbid conditions and smoking. RESULTS: During 31 378 patient-years of follow-up, 463 of 8908 patients died (standardised mortality ratio: 1.49 (95% CI 1.36 to 1.63)). Patients with persistent, highly active disease (mean DAS28 > 5.1) had a significantly higher mortality risk (adjusted HR (HRadj)=2.43; (95% CI 1.64 to 3.61)) than patients with persistently low disease activity (mean DAS28 < 3.2). Poor function and treatment with glucocorticoids > 5 mg/d was significantly associated with an increased mortality, independent of disease activity. Significantly lower mortality was observed in patients treated with tumour necrosis factor alpha (TNFalpha) inhibitors (HRadj=0.64 (95% CI 0.50 to 0.81), rituximab (HRadj=0.57 (95% CI 0.39 to 0.84), or other biologics (HRadj=0.64 (95% CI 0.42 to 0.99), compared to those receiving methotrexate. To account for treatment termination in patients at risk, an HRadj for patients ever exposed to TNFalpha inhibitors or rituximab was calculated. This resulted in an HRadj of 0.77 (95% CI 0.60 to 0.97). CONCLUSIONS: Patients with long-standing high disease activity are at substantially increased risk of mortality. Effective control of disease activity decreases mortality. TNFalpha inhibitors and rituximab seem to be superior to conventional DMARDs in reducing this risk.

Authors: J. Listing, J. Kekow, B. Manger, G. R. Burmester, D. Pattloch, A. Zink, A. Strangfeld

Date Published: 2015

Publication Type: Journal

Infections in patients with rheumatoid arthritis treated with biologic agents

Abstract (Expand)

OBJECTIVE: To estimate the incidence rates of serious and nonserious infections in patients with rheumatoid arthritis (RA) who start treatment with a biologic agent, and to compare these rates with … those in patients with RA who receive conventional treatment. METHODS: Patients enrolled in the German biologics register between May 2001 and September 2003 were included. Treating rheumatologists assessed adverse events and serious adverse events. All adverse events and serious adverse events experienced within 12 months after study entry were analyzed. Propensity score methods were applied to estimate which part of a rate increase was likely to be attributable to differences in patient characteristics. RESULTS: Data were available for 512 patients receiving etanercept, 346 patients receiving infliximab, 70 patients receiving anakinra, and 601 control patients treated with disease-modifying antirheumatic drugs. The total number of adverse events per 100 patient-years was 22.6 (95% confidence interval [95% CI] 18.7-27.2) among patients receiving etanercept, 28.3 (95% CI 23.1-34.7) among patients receiving infliximab, and 6.8 (95% CI 5.0-9.4) among controls (P < 0.0001). Significant differences in the rate of serious adverse events were also observed. For patients receiving etanercept, those receiving infliximab, and controls, the total numbers of serious adverse events per 100 patient-years were 6.4 (95% CI 4.5-9.1), 6.2 (95% CI 4.0-9.5), and 2.3 (95% CI 1.3-3.9), respectively (P = 0.0016). After adjusting for differences in the case patient mix, the relative risks of serious adverse events were 2.2 (95% CI 0.9-5.4) for patients receiving etanercept and 2.1 (95% CI 0.8-5.5) for patients receiving infliximab, compared with controls. CONCLUSION: Patients treated with biologic agents have a higher a priori risk of infection. However, our data suggest that this risk is increased by treatment with tumor necrosis factor inhibitors.

Authors: J. Listing, A. Strangfeld, S. Kary, R. Rau, U. von Hinueber, M. Stoyanova-Scholz, E. Gromnica-Ihle, C. Antoni, P. Herzer, J. Kekow, M. Schneider, A. Zink

Date Published: 2005

Publication Type: Journal

Does tumor necrosis factor alpha inhibition promote or prevent heart failure in patients with rheumatoid arthritis?

Abstract (Expand)

OBJECTIVE: To determine the hazard risk of developing or worsening heart failure in rheumatoid arthritis (RA) patients treated with tumor necrosis factor alpha (TNFalpha) inhibitors. METHODS: RA patients … ages 18-75 years who started treatment with infliximab, etanercept, or adalimumab (n = 2,757), or conventional disease-modifying antirheumatic drugs (controls; n = 1,491) at the time of enrollment in a German biologics register were studied. Cox proportional hazards models were applied to investigate the influence of disease-related and treatment-specific risk factors on the incidence or worsening of heart failure. RESULTS: The 3-year incidence rates of heart failure in patients with and patients without cardiovascular disease at the start of treatment were 2.2% and 0.4%, respectively. After adjustment for traditional cardiovascular risk factors, an increased risk of developing heart failure was found in patients who had a higher 28-joint Disease Activity Score at followup (hazard ratio [HR] 1.47 [95% confidence interval 1.07-2.02], P = 0.019). A residual nonsignificant risk related to treatment with TNFalpha inhibitors remained (adjusted HR 1.66 [95% confidence interval 0.67-4.1], P = 0.28). This residual risk was balanced by the efficacy of the anti-TNF treatment. When only baseline characteristics were taken into account, the HR related to TNFalpha inhibitor treatment decreased to 0.70 (95% confidence interval 0.27-1.84). CONCLUSION: The findings of this study indicate that TNFalpha inhibitor treatment that effectively reduces the inflammatory activity of RA is more likely to be beneficial than harmful with regard to the risk of heart failure, especially if there is no concomitant therapy with glucocorticoids or cyclooxygenase 2 inhibitors. Furthermore, the data suggest that TNFalpha inhibition does not increase the risk of worsening of prevalent heart failure.

Authors: J. Listing, A. Strangfeld, J. Kekow, M. Schneider, A. Kapelle, S. Wassenberg, A. Zink

Date Published: 2008

Publication Type: Journal

Clinical and functional remission: even though biologics are superior to conventional DMARDs overall success rates remain low–results from RABBIT, the German biologics register

Abstract (Expand)

We investigated the frequency of remission according to the disease activity score (DAS28) definition, modified American Rheumatology Association (ARA) criteria, and the frequency of an achievement of … a functional status above defined thresholds (’functional remission’, ’physical independence’) in rheumatoid arthritis (RA) patients treated with either biologics or conventional DMARDs. We used the data of a prospective cohort study, the German biologics register RABBIT (German acronym for Rheumatoid Arthritis–Observation of Biologic Therapy) to investigate the outcomes in RA patients with two or more DMARD failures who received new treatment with biologics (BIOL; n = 818) or a conventional DMARD (n = 265). Logistic regression analysis was applied to adjust for differences in baseline risks. Taking risk indicators such as previous DMARD failures or baseline clinical status into account, we found that biologics doubled the chance of remission compared to conventional DMARD therapies (DAS28 remission, adjusted odds ratio (OR) 1.95 (95% confidenece interval (CI) 1.2-3.2)); ARA remission, OR 2.05 (95% CI 1.2-3.5)). High remission rates (DAS28 remission, 30.6%; ARA remission, 16.9%) were observed in BIOL patients with a moderate disease activity (DAS28, 3.2 to 5.1) at the start of treatment. These rates decreased to 8.5% in patients with DAS28 > 6. Sustained remission at 6 and 12 months was achieved in <10% of the patients. Severely disabled patients (< or = 50% of full function) receiving biologic therapies were significantly more likely to achieve a status indicating physical independence (> or = 67% of full function) than controls (OR 3.88 (95% CI 1.7-8.8)). ’Functional remission’ (> or = 83% of full function) was more often achieved in BIOL than in controls (OR 2.18 (95% CI 1.04-4.6)). In conclusion, our study shows that biologics increase the chance to achieve clinical remission and a status of functional remission or at least physical independence. However, temporary or even sustained remission remain ambitious aims, which are achieved in a minority of patients only.

Authors: J. Listing, A. Strangfeld, R. Rau, J. Kekow, E. Gromnica-Ihle, T. Klopsch, W. Demary, G. R. Burmester, A. Zink

Date Published: 2006

Publication Type: Journal

Safety of vaccination against SARS-CoV-2 in people with rheumatic and musculoskeletal diseases: results from the EULAR Coronavirus Vaccine (COVAX) physician-reported registry

Abstract (Expand)

OBJECTIVES: To describe the safety of vaccines against SARS-CoV-2 in people with inflammatory/autoimmune rheumatic and musculoskeletal disease (I-RMD). METHODS: Physician-reported registry of I-RMD and … non-inflammatory RMD (NI-RMDs) patients vaccinated against SARS-CoV-2. From 5 February 2021 to 27 July 2021, we collected data on demographics, vaccination, RMD diagnosis, disease activity, immunomodulatory/immunosuppressive treatments, flares, adverse events (AEs) and SARS-CoV-2 breakthrough infections. Data were analysed descriptively. RESULTS: The study included 5121 participants from 30 countries, 90% with I-RMDs (n=4604, 68% female, mean age 60.5 years) and 10% with NI-RMDs (n=517, 77% female, mean age 71.4). Inflammatory joint diseases (58%), connective tissue diseases (18%) and vasculitis (12%) were the most frequent diagnostic groups; 54% received conventional synthetic disease-modifying antirheumatic drugs (DMARDs), 42% biological DMARDs and 35% immunosuppressants. Most patients received the Pfizer/BioNTech vaccine (70%), 17% AstraZeneca/Oxford and 8% Moderna. In fully vaccinated cases, breakthrough infections were reported in 0.7% of I-RMD patients and 1.1% of NI-RMD patients. I-RMD flares were reported in 4.4% of cases (0.6% severe), 1.5% resulting in medication changes. AEs were reported in 37% of cases (37% I-RMD, 40% NI-RMD), serious AEs in 0.5% (0.4% I-RMD, 1.9% NI-RMD). CONCLUSION: The safety profiles of SARS-CoV-2 vaccines in patients with I-RMD was reassuring and comparable with patients with NI-RMDs. The majority of patients tolerated their vaccination well with rare reports of I-RMD flare and very rare reports of serious AEs. These findings should provide reassurance to rheumatologists and vaccine recipients and promote confidence in SARS-CoV-2 vaccine safety in I-RMD patients.

Authors: P. M. Machado, S. Lawson-Tovey, A. Strangfeld, E. F. Mateus, K. L. Hyrich, L. Gossec, L. Carmona, A. Rodrigues, B. Raffeiner, C. Duarte, E. Hachulla, E. Veillard, E. Strakova, G. R. Burmester, G. K. Yardimci, J. A. Gomez-Puerta, J. Zepa, L. Kearsley-Fleet, L. Trefond, M. Cunha, M. Mosca, M. Cornalba, M. Soubrier, N. Roux, O. Brocq, P. Durez, R. Conway, T. Goulenok, J. W. Bijlsma, I. B. McInnes, X. Mariette

Date Published: 2022

Publication Type: Journal

EULAR recommendations for a core data set for pregnancy registries in rheumatology

Abstract (Expand)

BACKGROUND AND OBJECTIVE: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes … or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD. METHODS: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items. RESULTS: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering ’maternal information’, ’pregnancy’ and ’treatment’. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed. CONCLUSION: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.

Authors: Y. Meissner, R. Fischer-Betz, L. Andreoli, N. Costedoat-Chalumeau, D. De Cock, Rjem Dolhain, F. Forger, D. Goll, A. Molto, C. Nelson-Piercy, R. Ozdemir, L. Raio, S. C. Rodriguez-Garcia, S. Sciascia, M. Wallenius, A. Zbinden, A. Zink, A. Strangfeld

Date Published: 2021

Publication Type: Journal

Response to: ’Correspondence on ’EULAR recommendations for a core data set for pregnancy registries in rheumatology" by De Cock et al

Abstract

Not specified

Authors: Y. Meissner, R. Fischer-Betz, A. Zink, A. Strangfeld

Date Published: 2023

Publication Type: Journal

[Register and cohort studies : Overview of the most important data sources at the German Rheumatism Research Center]

Abstract (Expand)

Over the past 28 years the German Rheumatism Research Center in Berlin has initiated various epidemiological studies in which data on patients with inflammatory rheumatic diseases are collected nationwide … and multicentric. The spectrum ranges from rheumatoid arthritis and spondylarthritis to connective tissue diseases and rheumatic diseases in childhood. Based on the respective scientific question, studies of different types were established. The German National Databases for adults and children annually collect cross-sectional data to map the care of patients. In two inception cohorts, adults with early arthritis and patients with juvenile idiopathic arthritis are investigated from disease onset. The long-term observational cohorts/registries RABBIT, RABBIT-SpA and JuMBO focus on the long-term efficacy and safety of biologic drugs and other targeted treatments. Rhekiss investigates women with inflammatory rheumatic diseases when trying to become pregnant, during pregnancy and postpartum. This article highlights each of these observational studies with its characteristics as well as national and international collaborations.

Authors: Y. Meissner, F. Milatz, J. Callhoff, K. Minden, A. Regierer, A. Strangfeld

Date Published: 2020

Publication Type: Journal

Serious adverse events and the risk of stroke in patients with rheumatoid arthritis: results from the German RABBIT cohort

Abstract (Expand)

OBJECTIVE: In the general population, the incidence of stroke is increased following other serious events and hospitalisation. We investigated the impact of serious adverse events on the risk of stroke … in patients with rheumatoid arthritis (RA), taking risk factors and treatment into account. METHODS: Using data of the German biologics register RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) with 12354 patients with RA, incidence rates (IRs) and risk factors for stroke were investigated using multi-state and Cox proportional hazard models. In addition, in a nested case-control study, all patients with stroke were matched 1:2 to patients with identical baseline risk profile and analysed using a shared frailty model. RESULTS: During follow-up, 166 strokes were reported. The overall IR was 3.2/1000 patient-years (PY) (95% CI 2.7 to 3.7). It was higher after a serious adverse event (IR: 9.0 (7.3 to 11.0)), particularly within 30 days after the event (IR: 94.9 (72.6 to 121.9)). The adjusted Cox model showed increased risks of age per 5 years (HR: 1.4 (1.3 to 1.5)), hyperlipoproteinaemia (HR: 1.6 (1.0 to 2.5)) and smoking (HR: 1.9 (1.3 to 2.6)). The risk decreased with better physical function (HR: 0.9 (0.8 to 0.96)). In the case-control study, 163 patients were matched to 326 controls. Major risk factors for stroke were untreated cardiovascular disease (HR: 3.3 (1.5 to 7.2)) and serious infections (HR:4.4 (1.6 to 12.5)) or other serious adverse events (HR: 2.6 (1.4 to 4.8)). CONCLUSIONS: Incident adverse events, in particular serious infections, and insufficient treatment of cardiovascular diseases are independent drivers of the risk of stroke. Physicians should be aware that patients who experience a serious event are at increased risk of subsequent stroke.

Authors: Y. Meissner, A. Richter, B. Manger, H. P. Tony, E. Wilden, J. Listing, A. Zink, A. Strangfeld

Date Published: 2017

Publication Type: Journal

Pregnancy in women with psoriatic arthritis: A systematic literature review of disease activity and adverse pregnancy outcomes

Abstract (Expand)

BACKGROUND: There is limited robust evidence on the course of pregnancy and its outcomes in women with psoriatic arthritis (PsA) on which to base recommendations for the management of these patients. … OBJECTIVE: The primary objective was to review available data on (I) disease activity during pregnancy and on (II) adverse pregnancy outcomes (APO) in women with PsA. Secondly, neonatal outcomes and treatment of the rheumatic disease were investigated. METHODS: Systematic literature search within the databases Pubmed and Embase until 30 Nov 2020 was performed. Additionally, reference lists of included studies and of review articles revealed by the search were screened. All full text articles identified and published in English language were systematically evaluated by two reviewers. All studies that reported on one of the primary outcomes and included at least five pregnancies in women with PsA were considered. RESULTS: The review of 734 search results revealed 13 eligible publications reporting on a total of 2,332 pregnancies in women with PsA. Nine studies reported on PsA activity and showed an increase or worsening of disease activity after delivery compared to the pregnancy period. APOs were reported by nine studies. Adjusted analyses of APOs did not show an increased risk for gestational diabetes, small for gestational age and low birth weight in PsA patients in relation to the respective comparator groups. However, there were signals for a higher pre-eclampsia, elective caesarean section and preterm birth risk in PsA pregnancies. Meta-analysis was not performed due to study heterogeneity. DISCUSSION: This review showed a postpartum deterioration of disease activity in women with PsA and no risk elevation for gestational diabetes, small for gestational age and low birth weight. A higher risk for pre-eclampsia, elective caesarean section and preterm birth in PsA pregnancies cannot be ruled out. Differences in the studies investigated limit overall summary statements on disease activity and APOs in women with PsA. Harmonization of study approaches, instruments and outcome reporting is crucial to ensure informed counselling of patients with PsA before, during and after pregnancy that is based on robust data. PROSPERO REGISTRATION NUMBER: CRD42020162242.

Authors: Y. Meissner, T. Rudi, R. Fischer-Betz, A. Strangfeld

Date Published: 2021

Publication Type: Journal

Risk of major adverse cardiovascular events in patients with rheumatoid arthritis treated with conventional synthetic, biologic and targeted synthetic disease-modifying antirheumatic drugs: observational data from the German RABBIT register

Abstract (Expand)

OBJECTIVE: To estimate the effects of Janus kinase inhibitors (JAKi), tumour necrosis factor inhibitors (TNFi), other biologic(b) or conventional synthetic(cs) disease-modifying antirheumatic drugs … (DMARDs) on the risk of major adverse cardiovascular events (MACE) in patients with rheumatoid arthritis (RA). METHODS: Cohort study analysing episodes of DMARD-treatment initiated between January 2017 and April 2022 in the biologics register Rheumatoid Arthritis: Observation of Biologic Therapy. Incidence rates (IRs) per 100 patient-years with 95% CIs were calculated for overall patients and those with cardiovascular risk (age >/=50 years and >/=1 cardiovascular risk factor). MACE risk was estimated as HRs by inverse probability of treatment weight-adjusted Andersen-Gill models. RESULTS: A total of 154 MACE occurred among 14 203 treatment episodes (21 218 patient-years). IRs were 0.68 (0.47; 0.95), 0.62 (0.45; 0.83), 0.76 (0.53; 1.06) and 0.95 (0.68; 1.29) for JAKi, TNFi, bDMARDs and csDMARDs, respectively. IRs were higher in cardiovascular risk patients. Adjusted HRs (95% CI) comparing JAKi, bDMARDs and csDMARDs with TNFi were 0.89 (0.52 to 1.52), 0.76 (0.45; to1.27) and 1.36 (0.85 to 2.19) in overall, and 0.74 (0.41 to 1.31), 0.75 (0.45 to 1.27) and 1.21 (0.74 to 1.98) in cardiovascular risk patients. HRs were not increased in patients >/=65 years, with cardiovascular history or smokers, and also not when using csDMARD as reference instead of TNFi. IRs for baricitinib, tofacitinib and upadacitinib were 0.49 (0.25 to 0.85), 0.98 (0.58 to 1.55) and 0.53 (0.15 to 1.36), respectively. CONCLUSION: In this German observational cohort study, MACE did not occur more frequently with JAKi compared with other DMARDs. However, individual JAKis showed different unadjusted IRs.

Authors: Y. Meissner, M. Schafer, K. Albrecht, J. Kekow, S. Zinke, H. P. Tony, A. Strangfeld

Date Published: 2023

Publication Type: Journal

Incidence of facial nerve palsies stratified by DMARD treatment in patients with rheumatoid arthritis: data from the RABBIT register

Abstract

Not specified

Authors: Y. Meissner, M. Schafer, M. Schneider, E. Wilden, S. Zinke, A. Zink, A. Strangfeld

Date Published: 2020

Publication Type: Journal

[Insights into pregnancy and breastfeeding in inflammatory rheumatic diseases through observational data]

Abstract (Expand)

Information on pregnancy and breastfeeding in women with chronic inflammatory rheumatic diseases is relevant for a successful pregnancy and also for maternal and child health. In general, pregnant and … breastfeeding women are excluded from randomized clinical trials and therefore evidence for clinical care and counselling has to be generated from observational studies. In the past decades, various data collections have been established for this purpose in addition to the existing spontaneous reporting systems initiated by drug authorities, with the aim of monitoring the teratogenic risk of a drug. Health insurance claims data, electronic health records and Scandinavian registers are also increasingly being used for research on pregnancy-associated events; however, all these data sources lack the inclusion of the maternal disease, especially with respect to its inflammatory component. Established cohort studies, biologics and disease registries record disease activity but are not designed for pregnancy-specific questions. Pregnancy registries and studies in rheumatology close this gap. In order to be able to make a better assessment of the possibilities and limitations of existing data sources on pregnancy and lactation, they are presented in detail in the following review including their respective advantages and disadvantages and examples from rheumatology are given. In addition, existing collaborations as well as studies for investigating the influence of paternal rheumatic disease are highlighted.

Authors: Y. Meissner, A. Strangfeld

Date Published: 2021

Publication Type: Journal

[Latest findings from the RABBIT register]

Abstract (Expand)

Since 2001 rheumatologists throughout Germany have been recruiting patients with rheumatoid arthritis into the biologics register (rheumatoid arthritis: observation of biologics treatment, RABBIT) to … investigate the long-term safety and efficacy of modern antirheumatic treatment. Over the past 20 years more than 20,000 patients have been enrolled in the prospective cohort study. This article summarizes the research findings published in 2020/2021, focusing on safety aspects, factors influencing treatment efficacy and patient-reported outcomes. With herpes zoster, facial nerve palsy and psoriasis, several adverse events were investigated that were either reported as a safety signal from clinical trials or through the EudraVigilance database or occurred as a paradoxical reaction under drug treatment. For these events, the influence of biological disease-modifying antirheumatic drug (DMARD) treatment was analyzed. In the publication on herpes zoster, we also considered drug treatment with Janus kinase inhibitors. Severe overweight can influence the success of treatment. There are gender-specific differences and the mode of action of a treatment also determines whether obesity reduces the response to treatment. The majority of patients observed in RABBIT were satisfied with the treatment they have received after 1 year. We were able to show which factors either favor or negatively influence satisfaction with the effectiveness and safety of the treatment. This review article shows that long-term observational studies such as the RABBIT register contribute to the understanding of treatment risks and can identify factors that influence the effects of treatment even after two decades of data collection.

Authors: Y. Meissner, A. Strangfeld

Date Published: 2022

Publication Type: Journal

European Network of Pregnancy Registers in Rheumatology (EuNeP)-an overview of procedures and data collection

Abstract (Expand)

BACKGROUND: The collaborative initiative of the European Network of Pregnancy Registers in Rheumatology (EuNeP) aims to combine data available in nationwide pregnancy registers to increase knowledge … on pregnancy outcomes in women with inflammatory rheumatic diseases (IRD) and on drug safety during pregnancy and lactation. The objective of this study was to describe the similarities and differences of the member registers. METHODS: From all registers, information about their structure and design was collected, as well as which parameters regarding demographics, maternal outcomes, treatment, course and outcome of pregnancy, and development of the child were available in the respective datasets. Furthermore, the current recruitment status was reported. RESULTS: The four registers (EGR2 (France), RePreg (Switzerland), RevNatus (Norway), and Rhekiss (Germany)) collect information prospectively and nationwide. Patients can be enrolled before conception or during pregnancy. To date, more than 3500 patients in total have been included, and data on 2200 pregnancies with an outcome are available. The distribution of diagnoses in the respective registers varies considerably, and only three entities (rheumatoid arthritis, psoriatic arthritis, and spondyloarthritis) are captured by all the registers. Broad consistency was found in non-disease-specific data items, but differences regarding instruments and categories as well as frequency of data collection were revealed. Disease-specific data items are less homogeneously collected. CONCLUSION: Although the registers in this collaboration have similar designs, we found numerous differences in the variables collected. This survey of the status quo of current pregnancy registers is the first step towards identifying data collected uniformly across registers in order to facilitate joint analyses. TRIAL REGISTRATION: Not applicable.

Authors: Y. Meissner, A. Strangfeld, N. Costedoat-Chalumeau, F. Forger, D. Goll, A. Molto, R. Ozdemir, M. Wallenius, R. Fischer-Betz

Date Published: 2019

Publication Type: Journal

Pregnancy and neonatal outcomes in women with axial spondyloarthritis: pooled data analysis from the European Network of Pregnancy Registries in Rheumatology (EuNeP)

Abstract (Expand)

OBJECTIVE: To investigate outcome and course of pregnancies in women with axial spondyloarthritis (axSpA) in a pooled data analysis of pregnancy registries in rheumatology. METHODS: Prospectively … followed women with axSpA, fulfilling ASAS classification criteria and for whom a pregnancy outcome was reported, were eligible for the analysis. Anonymised data of four registries was pooled. Rates of adverse pregnancy outcomes were calculated. Systemic inflammation, disease activity and treatment patterns with tumour necrosis factor inhibitor (TNFi) before, during and after pregnancy were analysed. RESULTS: In a total of 332 pregnancies from 304 axSpA women, 98.8% of the pregnancies resulted in live birth. Mean maternal age was 31 years and disease duration 5 years. Most of these patients received pre-conception counselling (78.4%). Before pregnancy, 53% received TNFi treatment, 27.5% in first and 21.4% in third trimester. Pregnancy and neonatal outcomes were favourable with rates of 2.2% for pre-eclampsia, 4.9% for preterm birth, 3.1% for low birth weight and 9.5% for small for gestational age. Neonates were delivered by caesarean section in 27.7% of pregnancies, of which 47.4% were emergencies. Pooled mean CRP was 4 mg/L before conception peaking in the second trimester at 9.4 mg/L. Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was below 4 at all time-points. CONCLUSIONS: Pooled rates of most outcomes were better than what had been reported in the literature and within expected rates of those reported for the general population. Pre-conception counselling, planned pregnancies and a tight management in expert centres applying a tailored treatment approach may have contributed to the favourable pregnancy outcomes.

Authors: Y. Meissner, A. Strangfeld, A. Molto, F. Forger, M. Wallenius, N. Costedoat-Chalumeau, H. Bjorngaard, M. Couderc, R. M. Flipo, G. Guettrot-Imbert, I. Haase, B. Jakobsen, H. S. S. Koksvik, C. Richez, J. Sellam, A. Weiss, A. Zbinden, R. Fischer-Betz, P. collaborator group EuNe

Date Published: 2022

Publication Type: Journal

Impact of disease activity and treatment of comorbidities on the risk of myocardial infarction in rheumatoid arthritis

Abstract (Expand)

BACKGROUND: The aim was to estimate the impact of individual risk factors and treatment with various disease-modifying antirheumatic drugs (DMARDs) on the incidence of myocardial infarction (MI) in … patients with rheumatoid arthritis (RA). METHODS: We analysed data from 11,285 patients with RA, enrolled in the prospective cohort study RABBIT, at the start of biologic (b) or conventional synthetic (cs) DMARDs. A nested case-control study was conducted, defining patients with MI during follow-up as cases. Cases were matched 1:1 to control patients based on age, sex, year of enrolment and five cardiovascular (CV) comorbidities. Generalized linear models were applied (Poisson regression with a random component, conditional logistic regression). RESULTS: In total, 112 patients developed an MI during follow-up. At baseline, during the first 6 months of follow-up and prior to the MI, inflammation markers (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) but not 28-joint-count disease activity score (DAS28) were significantly higher in MI cases compared to matched controls and the remaining cohort. Baseline treatment with DMARDs was similar across all groups. During follow-up bDMARD treatment was significantly more often discontinued or switched in MI cases. CV comorbidities were significantly less often treated in MI cases vs. matched controls (36 % vs. 17 %, p < 0.01). In the adjusted regression model, we found a strong association between higher CRP and MI (OR for log-transformed CRP at follow-up: 1.47, 95 % CI 1.00; 2.16). Furthermore, treatment with prednisone >/=10 mg/day (OR 1.93, 95 % CI 0.57; 5.85), TNF inhibitors (OR 0.91, 95 % CI 0.40; 2.10) or other bDMARDs (OR 0.85, 95 % CI 0.27; 2.72) was not associated with higher MI risk. CONCLUSIONS: CRP was associated with risk of MI. Our results underline the importance of tight disease control taking not only global disease activity, but also CRP as an individual marker into account. It seems irrelevant with which class of (biologic or conventional) DMARD effective control of disease activity is achieved. However, in some patients the available treatment options were insufficient or insufficiently used - regarding DMARDs to treat RA as well as regarding the treatment of CV comorbidities.

Authors: Y. Meissner, A. Zink, J. Kekow, K. Rockwitz, A. Liebhaber, S. Zinke, K. Gerhold, A. Richter, J. Listing, A. Strangfeld

Date Published: 2016

Publication Type: Journal

Risk of invasive melanoma in patients with rheumatoid arthritis treated with biologics: results from a collaborative project of 11 European biologic registers

Abstract (Expand)

OBJECTIVES: Some studies have reported a possible association between exposure to tumour necrosis factor (TNF) inhibitors and an increased risk of melanoma. The aim of this study was to investigate the … incidence of invasive cutaneous melanomas in patients with rheumatoid arthritis (RA) treated with TNF inhibitors (TNFi), other biologic disease modifying drugs and non-biologic therapy. METHODS: Eleven biologic registers from nine European countries participated in this collaborative project. According to predefined exposure definitions, cohorts of patients with RA were selected. Using the country-specific general population of each register as reference, age, sex and calendar year standardised incidence ratios (SIRs) of invasive histology-confirmed cutaneous melanoma were calculated within each register. Pooled SIR and incidence rate ratios (IRRs) comparing biologic cohorts to biologic-naive were calculated across countries by taking the size of the register into account. RESULTS: Overall 130 315 RA patients with a mean age of 58 years contributing 579 983 person-years were available for the analysis and 287 developed a first melanoma. Pooled SIRs for biologic-naive, TNFi and rituximab-exposed patients were 1.1 (95% CI 0.9 to 1.4), 1.2 (0.99 to 1.6) and 1.3 (0.6 to 2.6), respectively. Incidence rates in tocilizumab and abatacept-exposed patients were also not significantly increased. IRR versus biologic-naive patients were: TNFi 1.1 (95% CI 0.8 to 1.6); rituximab 1.2 (0.5 to 2.9). CONCLUSIONS: This large European collaborative project did not confirm an overall increased risk of melanoma following exposure to TNFi.

Authors: L. K. Mercer, J. Askling, P. Raaschou, W. G. Dixon, L. Dreyer, M. L. Hetland, A. Strangfeld, A. Zink, X. Mariette, A. Finckh, H. Canhao, F. Iannone, J. Zavada, J. Morel, J. E. Gottenberg, K. L. Hyrich, J. Listing

Date Published: 2017

Publication Type: Journal

Spectrum of lymphomas across different drug treatment groups in rheumatoid arthritis: a European registries collaborative project

Abstract (Expand)

BACKGROUND: Lymphomas comprise a heterogeneous group of malignant diseases with highly variable prognosis. Rheumatoid arthritis (RA) is associated with a twofold increased risk of both Hodgkin’s lymphoma … (HL) and non-Hodgkin’s lymphoma (NHL). It is unknown whether treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) affect the risk of specific lymphoma subtypes. METHODS: Patients never exposed to (bionaive) or ever treated with bDMARDs from 12 European biologic registers were followed prospectively for the occurrence of first ever histologically confirmed lymphoma. Patients were considered exposed to a bDMARD after having received the first dose. Lymphomas were attributed to the most recently received bDMARD. RESULTS: Among 124 997 patients (mean age 59 years; 73.7% female), 533 lymphomas were reported. Of these, 9.5% were HL, 83.8% B-cell NHL and 6.8% T-cell NHL. No cases of hepatosplenic T-cell lymphoma were observed. Diffuse large B-cell lymphoma (DLBCL) was the most frequent B-cell NHL subtype (55.8% of all B-cell NHLs). The subtype distributions were similar between bionaive patients and those treated with tumour necrosis factor inhibitors (TNFi). For other bDMARDs, the numbers of cases were too small to draw any conclusions. Patients with RA developed more DLBCLs and less chronic lymphocytic leukaemia compared with the general population. CONCLUSION: This large collaborative analysis of European registries has successfully collated subtype information on 533 lymphomas. While the subtype distribution differs between RA and the general population, there was no evidence of any modification of the distribution of lymphoma subtypes in patients with RA treated with TNFi compared with bionaive patients.

Authors: L. K. Mercer, A. C. Regierer, X. Mariette, W. G. Dixon, E. Baecklund, K. Hellgren, L. Dreyer, M. L. Hetland, R. Cordtz, K. Hyrich, A. Strangfeld, A. Zink, H. Canhao, M. V. Hernandez, F. Tubach, J. E. Gottenberg, J. Morel, J. Zavada, F. Iannone, J. Askling, J. Listing

Date Published: 2017

Publication Type: Journal

[The what, the how and the why in rheumatological research]

Abstract

Not specified

Authors: K. Minden, A. Radbruch, G. R. Burmester, A. Strangfeld

Date Published: 2020

Publication Type: Journal

[The first biologic for rheumatoid arthritis: factors influencing the therapeutic decision]

Abstract (Expand)

BACKGROUND AND AIMS: Biologics (disease modifying antirheumatic drugs, bDMARD) have been in use in Germany for the treatment of rheumatoid arthritis (RA) since 2001, usually after failure of at least … one conventional synthetic (cs)DMARD. We analyzed temporal changes in factors that influence the decision for either a first bDMARD or a further csDMARD. MATERIAL AND METHODS: We analyzed data from 9513 bDMARD-naive RA patients in the German biologics register RABBIT who switched to a new therapy. For three recruitment periods (2001-2003, 2004-2006 and 2009-2015) factors influencing the therapeutic decision were analyzed by means of machine learning methods and logistic regression analysis. RESULTS: In all recruitment periods the number of previous csDMARDs, high dosages of glucocorticoids (>7.5 mg/day) and a higher DAS28 (>5.1) were significantly associated with the decision for a first bDMARD. Over time, the chance of receiving a bDMARD increased in patients with moderate disease activity, moderate glucocorticoid dosages (5-7.5 mg/day) and those with comorbidities, such as congestive heart failure or prior malignancy. Men had a higher chance of receiving a bDMARD than women only in the first recruitment period. Private health insurance, high education and gainful employment were significantly associated with more frequent prescription of bDMARDs in all recruitment periods. DISCUSSION: The time-dependent changes in the impact of disease activity, concomitant drugs, gender and comorbidity on the prescription of bDMARDs mirror the increasing therapeutic options and the growing experience in the application of the new substances in patients at higher risk. The influence of demographic and social factors may reflect safety concerns in patients at increased risk of adverse events but also the need to economize drug costs..

Authors: D. Pattloch, A. Richter, B. Manger, R. Dockhorn, L. Meier, H. P. Tony, A. Zink, A. Strangfeld

Date Published: 2017

Publication Type: Journal

After JAK inhibitor failure: to cycle or to switch, that is the question - data from the JAK-pot collaboration of registries

Abstract (Expand)

OBJECTIVES: The expanded therapeutic arsenal in rheumatoid arthritis (RA) raises new clinical questions. The objective of this study is to compare the effectiveness of cycling Janus kinase inhibitors … (JAKi) with switching to biologic disease-modifying antirheumatic drug (bDMARD) in patients with RA after failure to the first JAKi. METHODS: This is a nested cohort study within data pooled from an international collaboration of 17 national registries (JAK-pot collaboration). Data from patients with RA with JAKi treatment failure and who were subsequently treated with either a second JAKi or with a bDMARD were prospectively collected. Differences in drug retention rates after second treatment initiation were assessed by log-rank test and Cox regression analysis adjusting for potential confounders. Change in Clinical Disease Activity Index (CDAI) over time was estimated using a linear regression model, adjusting for confounders. RESULTS: 365 cycling and 1635 switching patients were studied. Cyclers were older and received a higher number of previous bDMARDs. Both strategies showed similar observed retention rates after 2 years of follow-up. However, adjusted analysis revealed that cycling was associated with higher retention (p=0.04). Among cyclers, when the first JAKi was discontinued due to an adverse event (AE), it was more likely that the second JAKi would also be stopped due to an AE. Improvement in CDAI over time was similar in both strategies. CONCLUSIONS: After failing the first JAKi, cycling JAKi and switching to a bDMARD appear to have similar effectiveness. Caution is advised if an AE was the reason to stop the first JAKi.

Authors: M. Pombo-Suarez, C. Sanchez-Piedra, J. Gomez-Reino, K. Lauper, D. Mongin, F. Iannone, K. Pavelka, D. C. Nordstrom, N. Inanc, C. Codreanu, K. L. Hyrich, D. Choquette, A. Strangfeld, B. F. Leeb, Z. Rotar, A. Rodrigues, E. K. Kristianslund, T. K. Kvien, O. Elkayam, G. Lukina, S. A. Bergstra, A. Finckh, D. S. Courvoisier

Date Published: 2023

Publication Type: Journal

Impact of systemic inflammation and disease activity on the incidence of interstitial lung disease in patients with rheumatoid arthritis - a nested case-control study within the German biologics register RABBIT

Abstract (Expand)

BACKGROUND: To investigate the association between the development of incident interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA) and the disease activity of RA with its various … components, especially C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). METHODS: We analysed data from RA patients, observed in the German biologics register RABBIT between 2001 and 2021. In a nested case-control study, patients with a reported incident ILD diagnosis during follow-up were matched 1:5 to patients without ILD. Matching criteria were sex, age, RA duration, date of enrolment and observation time. Defined by a directed acyclic graph (DAG), we adjusted the conditional logistic regression models for rheumatoid factor, smoking, chronic obstructive pulmonary disease and tuberculosis/chronic viral infections to investigate the impact of disease activity/systemic inflammation. Mean and categorized values were analysed within 12 months prior to ILD and during the entire observation time. Additionally, two sensitivity analyses were performed, using validated ILD cases only and considering ILD cases with an observation time of more than 12 months. RESULTS: We identified 139 RA patients with incident ILD and matched them to 686 controls. In 94 cases the diagnosis could be validated, and 98 cases had a follow-up of > 12 months. The averaged DAS28 composite score (including ESR or CRP) was not associated with developing RA-ILD (odds ratios 1.16 [95% confidence interval: 0.97-1.40] and 1.06 [0.86-1.29], respectively). However, single measures of inflammation, log ESR (1.86 [1.35-2.57]) and log CRP (1.55 [1.21-1.97]), were significantly associated with an increased RA-ILD risk. A higher risk for ILD was also revealed for persistently high inflammation. Other DAS28 components showed no significant associations with RA-ILD. These results were consistent for values over the entire observation time of a patient and within 12 months prior to the ILD. Sensitivity analyses confirmed these findings. CONCLUSION: Higher levels of systemic inflammation, as indicated by ESR and CRP, but not joint counts or patient’s global assessment, were significantly associated with the occurrence of incident ILD in patients with RA. As possible predictor for the development of RA-ILD, systemic inflammation should be monitored closely and independently of joint count results.

Authors: R. Ramien, T. Rudi, R. Alten, A. Krause, M. Schneider, M. Schaefer, A. Strangfeld, Y. Meissner

Date Published: 2024

Publication Type: Journal

Risk of herpes zoster (shingles) in patients with rheumatoid arthritis under biologic, targeted synthetic and conventional synthetic DMARD treatment: data from the German RABBIT register

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OBJECTIVE: To compare event and incidence rates of herpes zoster (HZ), also known as shingles, in patients with rheumatoid arthritis under treatment with conventional synthetic (cs), targeted synthetic … (ts) or biologic (b) disease-modifying antirheumatic drugs (DMARDs). METHODS: Patients were prospectively enrolled from 2007 until October 2020. Reported HZ events were assigned to ongoing treatments or those terminated within 1 month prior to the HZ event. Exposure-adjusted event rates (EAERs) of HZ were calculated per 1000 patient years (py) and adjusted HRs with 95% CIs computed. Inverse probability weights (IPW) were used to adjust for confounding by indication. RESULTS: Data of 13 991 patients (62 958 py) were analysed, with 559 HZ events reported in 533 patients. The EAER of HZ was highest for tsDMARDs (21.5, 95% CI 16.4 to 27.9), followed by B cell targeted therapy (10.3, 95% CI 8.0 to 13.0), monoclonal antitumour necrosis factor (anti-TNF) antibodies (9.3, 95% CI 7.7 to 11.2), interleukin 6 inhibitors (8.8, 95% CI 6.9 to 11.0), soluble TNF receptor fusion protein (8.6, 95% CI 6.8 to 10.8), T cell costimulation modulator (8.4, 95% CI 5.9 to 11.8) and csDMARDs (7.1, 95% CI 6.0 to 8.3). Adjusted for age, sex and glucocorticoids and weighted with IPW, tsDMARDs (HR 3.66, 95% CI 2.38 to 5.63), monoclonal anti-TNF antibodies (HR 1.63, 95% CI 1.17 to 2.28) and B cell targeted therapy (HR 1.57, 95% CI 1.03 to 2.40) showed a significantly higher risk compared with csDMARDs. CONCLUSION: Our results provide evidence for a 3.6-fold increased risk of HZ associated with tsDMARDs and an increased risk of HZ under bDMARDs compared with csDMARDs.

Authors: I. Redeker, K. Albrecht, J. Kekow, G. R. Burmester, J. Braun, M. Schafer, A. Zink, A. Strangfeld

Date Published: 2022

Publication Type: Journal

TNFi is associated with positive outcome, but JAKi and rituximab are associated with negative outcome of SARS-CoV-2 infection in patients with RMD

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INTRODUCTION: Several risk factors for severe COVID-19 specific for patients with inflammatory rheumatic and musculoskeletal diseases (RMDs) have been identified so far. Evidence regarding the influence … of different RMD treatments on outcomes of SARS-CoV-2 infection is still poor. METHODS: Data from the German COVID-19-RMD registry collected between 30 March 2020 and 9 April 2021 were analysed. Ordinal outcome of COVID-19 severity was defined: (1) not hospitalised, (2) hospitalised/not invasively ventilated and (3) invasively ventilated/deceased. Independent associations between demographic and disease features and outcome of COVID-19 were estimated by multivariable ordinal logistic regression using proportional odds model. RESULTS: 2274 patients were included. 83 (3.6%) patients died. Age, male sex, cardiovascular disease, hypertension, chronic lung diseases and chronic kidney disease were independently associated with worse outcome of SARS-CoV-2 infection. Compared with rheumatoid arthritis, patients with psoriatic arthritis showed a better outcome. Disease activity and glucocorticoids were associated with worse outcome. Compared with methotrexate (MTX), TNF inhibitors (TNFi) showed a significant association with better outcome of SARS-CoV-2 infection (OR 0.6, 95% CI0.4 to 0.9). Immunosuppressants (mycophenolate mofetil, azathioprine, cyclophosphamide and ciclosporin) (OR 2.2, 95% CI 1.3 to 3.9), Janus kinase inhibitor (JAKi) (OR 1.8, 95% CI 1.1 to 2.7) and rituximab (OR 5.4, 95% CI 3.3 to 8.8) were independently associated with worse outcome. CONCLUSION: General risk factors for severity of COVID-19 play a similar role in patients with RMDs as in the normal population. Influence of disease activity on COVID-19 outcome is of great importance as patients with high disease activity-even without glucocorticoids-have a worse outcome. Patients on TNFi show a better outcome of SARS-CoV-2 infection than patients on MTX. Immunosuppressants, rituximab and JAKi are associated with more severe course.

Authors: A. C. Regierer, R. Hasseli, M. Schafer, B. F. Hoyer, A. Krause, H. M. Lorenz, A. Pfeil, J. Richter, T. Schmeiser, H. Schulze-Koops, A. Strangfeld, R. E. Voll, C. Specker, U. Mueller-Ladner

Date Published: 2021

Publication Type: Journal

The Sensitivity to Change of the ASAS Health Index in an Observational Real-Life Cohort Study

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OBJECTIVE: The Assessment of Spondyloarthritis international Society Health Index (ASAS HI) measures global functioning and health in patients with axial spondyloarthritis (axSpA) covering domains of … physical, emotional, and social functioning. The main aim of this study was to investigate the sensitivity to change of ASAS HI in comparison with established variables of disease activity, function, and mental health. METHODS: Patients with axSpA from the disease register RABBIT-SpA with follow-up time of at least 12 months and available ASAS HI questionnaires were included. Patients received questionnaires addressing disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS]), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]), mental health (5-item World Health Organization Well-Being Index [WHO-5]), and global functioning (ASAS HI). Standardized response means (SRMs) were calculated to compare the sensitivity to change of different variables. RESULTS: Six hundred and sixty-seven patients were included, 552 treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and 115 with conventional synthetic DMARDs and/or nonsteroidal antiinflammatory drugs (control group). Between baseline and month 12, the mean ASAS HI declined from 6.9 to 5.1 in the bDMARD group and from 5.9 to 5.6 in the conventionally treated group. In the bDMARD group, the SRM of ASAS HI was 0.52, compared to 0.59 for BASFI, 0.65 for WHO-5, 0.73 for BASDAI, and 0.90 for ASDAS. The following ASAS HI domains were most frequently affected: pain (78% agreed), maintaining body position (75%), and energy/drive (73%). In the patients receiving bDMARDs, there was an improvement in all items. In the control group, the largest improvement was seen in pain. CONCLUSION: As expected, ASDAS and BASDAI as disease activity scores showed high sensitivity to change, whereas changes in physical function (BASFI), mental health (WHO-5), and the broader concept of functioning and health (ASAS HI) were moderate.

Authors: A. C. Regierer, A. Weiss, U. Kiltz, J. Sieper, I. Schwarze, M. Bohl-Buhler, H. Kellner, D. Poddubnyy, A. Zink, J. Braun, J. Listing, A. Strangfeld

Date Published: 2023

Publication Type: Journal

Impact of treatment with biologic DMARDs on the risk of sepsis or mortality after serious infection in patients with rheumatoid arthritis

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OBJECTIVE: This observational cohort study investigated the impact of biological (b) disease-modifying antirheumatic drugs (DMARDs) on the outcomes of serious infections (SIs) in patients with rheumatoid … arthritis. METHODS: We investigated outcomes of SIs observed in 947 patients enrolled in the German biologics register RABBIT(Rheumatoid arthritis: observation of biologic therapy). Outcomes were (1) recovery without complication, (2) sepsis following SI (</=30 days), and (3) death after SI without known sepsis (</=90 days). We applied a multinomial generalised estimating equation model for longitudinal data to evaluate the risks of sepsis and death simultaneously. RESULTS: Sepsis within 30 days after SI was reported in 135 out of 947 patients, 85 of these had a fatal outcome. Fifty-three patients died within 90 days after SI without known sepsis. The adjusted risk of developing sepsis increased with age and was higher in patients with chronic renal disease. Compared with conventional synthetic (cs)DMARDs, the risk was significantly lower when patients were exposed to bDMARDs at the time of SI (OR: 0.56, 95% CI 0.38 to 0.81). Risk factors of fatal SI were higher age, use of glucocorticoids at higher doses and heart failure. Patients treated with bDMARDs and those with better physical function had a significantly lower mortality risk. CONCLUSIONS: These results suggest a beneficial effect of bDMARDs on the risk of sepsis after SI and the risk of a fatal outcome. Successful immunosuppression may prevent an unregulated host response to SI, that is, the escalation to sepsis. Further investigation is needed to validate these results.

Authors: A. Richter, J. Listing, M. Schneider, T. Klopsch, A. Kapelle, J. Kaufmann, A. Zink, A. Strangfeld

Date Published: 2016

Publication Type: Journal

Primary and secondary patient data in contrast: the use of observational studies like RABBIT

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The study of secondary patient data, particularly represented by claims data, has increased in recent years. The strength of this approach involves easy access to data that have been generated for … administrative purposes. By contrast, collection of primary data for research is time-consuming and may therefore appear outdated. Both administrative data and data collected prospectively in clinical care can address similar research questions concerning effectiveness and safety of treatments. Therefore, why should we invest the precious time of rheumatologists to generate primary patient data? This article will outline some features of primary patient data collection illustrated by the German biologics register RABBIT (Rheumatoid arthritis: observation of biologic therapy). RABBIT is a long-term observational cohort study that was initiated more than 15 years ago. We will discuss as quality indicators: (i) study design, (ii) type of documentation, standardisation of (iii) clinical and (iv) safety data, (v) monitoring of the longitudinal follow-up, (vi) losses to follow-up as well as (vii) the possibilities to link the data base. The impact of these features on interpretation and validity of results is illustrated using recent publications. We conclude that high quality and completeness of data prospectively-collected offers many advantages over large quantities of non-standardised data collected in an unsupervised manner. We expect the enthusiasm about the use of secondary patient data to decline with more awareness of their methodological limitations while studies with primary patient data like RABBIT will maintain and broaden their impact on daily clinical practice.

Authors: A. Richter, Y. Meissner, A. Strangfeld, A. Zink

Date Published: 2016

Publication Type: Journal

Sustainability of rituximab therapy in different treatment strategies: results of a 3-year followup of a German biologics register

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OBJECTIVE: To compare the approved treatment of rheumatoid arthritis using rituximab + methotrexate (RTX + MTX) versus the off-label treatment variants of RTX in monotherapy or RTX in combination with … leflunomide (RTX + LEF). METHODS: We included RTX-naive patients enrolled in the German biologics register RABBIT (Rheumatoid Arthritis: Observation of Biologic Therapy) between 2007 and 2012 (n = 907) who started treatment with RTX. Three treatment regimens (RTX + MTX, RTX + LEF, and RTX monotherapy) were analyzed regarding therapy discontinuation, dropout, RTX retreatment, and concomitant glucocorticoid therapy. Effectiveness was evaluated with linear mixed models. RESULTS: Baseline patient characteristics were similar across treatment regimens, except for poorer functional status and more comorbidities in RTX monotherapy. Average doses of glucocorticoids were lower in RTX + LEF compared to the 2 other groups. The frequency and timing of RTX retreatment (P > 0.62) as well as improvement in the Disease Activity Score in 28 joints (DAS28) over time (P > 0.15) were similar in all treatment regimens. Within the first 12 months of treatment, the DAS28 decreased by 1.5 units, and between months 12 and 36, by a further 0.4 unit equally in all groups. Nevertheless, therapy discontinuation and dropout were significantly increased on RTX monotherapy (hazard ratio [HR] 1.7 [95% confidence interval (95% CI) 1.2-2.3]), and additionally when patients were rheumatoid factor negative (HR 1.5 [95% CI 1.0-2.1]). CONCLUSION: In patients who continue therapy, RTX + LEF, RTX monotherapy, and RTX + MTX seem to be equally effective. However, given the lower adherence rates on monotherapy, this treatment option is not sufficient for all patients. Since many patients are intolerant to MTX, more licensed RTX treatment options are needed.

Authors: A. Richter, A. Strangfeld, P. Herzer, E. Wilden, A. Bussmann, J. Listing, A. Zink

Date Published: 2014

Publication Type: Journal

Mobile Responsive App-A Useful Additional Tool for Data Collection in the German Pregnancy Register Rhekiss?

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Background: The German pregnancy register Rhekiss is designed as a nationwide, web-based longitudinal observational cohort established in 2015. The register follows women with inflammatory rheumatic … disease prospectively from child wish or early pregnancy until 2 years post-partum. Information on clinical and laboratory parameters, drug treatment, and (adverse) pregnancy outcomes are documented in pre-specified intervals. Physicians and patients report data for the same time periods via separated accounts and forms into a web-based application (app). As data entry on mobile devices might improve response rates of patients, a responsive app as a further convenient documentation option was developed. Methods: The Rhekiss-app is available for self-reported data retrieval since August 2017 from the App stores. For the current analysis, Rhekiss register data were used from the start of the register until 30 September 2020. The analyses were performed for forms containing information on devices. Outcome parameters were compared for mobile and desktop users for the quantity and quality of filled forms. Results: In total, 5,048 forms were received and submitted by 966 patients. About 57% of forms were sent from mobile devices with the highest numbers in patients with child wishes (63%). Users of mobile devices were slightly younger and often had less high-education level (62 vs. 79%) compared with desktop users. The proportion of forms submitted via mobile devices increased steadily from 48% in the fourth quarter of 2018 to 64% in the third quarter of 2020. The proportion of forms received before and after the Rhekiss-app implementation increased with the highest increase of 12% for forms filled at time point 12 months post-partum. Mobile users submitted significantly more forms than desktop users (2.9 vs. 2.1), data sent via desktops were more often complete (88 vs. 86%). Conclusion: The responsive app is a valuable additional tool for data collection and is well-accepted by patients as indicated by its increasing use in Rhekiss. Apart from desktop/browser developments, the technological adoptions within observational cohorts and registries should take smartphone requirements and developments into account, especially when patient-reported data in young, mobile patients are collected, bearing in mind that data quality could be compromised and concepts for improving data quality should be implemented.

Authors: J. G. Richter, A. Weiss, C. Bungartz, R. Fischer-Betz, A. Zink, M. Schneider, A. Strangfeld

Date Published: 2021

Publication Type: Journal

Impact of DMARD treatment and systemic inflammation on all-cause mortality in patients with rheumatoid arthritis and interstitial lung disease: a cohort study from the German RABBIT register

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OBJECTIVES: To investigate the impact of disease activity and treatment with disease-modifying antirheumatic drugs (DMARDs) on all-cause mortality in patients with rheumatoid arthritis and prevalent … interstitial lung disease (RA-ILD). METHODS: Patients with RA-ILD were selected from the biologics register Rheumatoid Arthritis: Observation of Biologic Therapy (RABBIT). Using time-varying Cox regression, the association between clinical measures and mortality was investigated. The impact of DMARDs was analysed by (1) Cox regression considering cumulative exposure (ie, treatment months divided by total months) and (2) time-varying Cox regression as main approach (treatment exposures at monthly level). RESULTS: Out of 15 566 participants, 381 were identified as RA-ILD cases with 1258 person-years of observation and 2.6 years median length of follow-up. Ninety-seven patients (25.5%) died and 34 (35.1%) of these were not receiving DMARD therapy at the time of death. Higher inflammatory biomarkers but not swollen and tender joint count were significantly associated with mortality. Compared with tumour necrosis factor inhibitors (TNFi), non-TNFi biologic DMARDs (bDMARDs) exhibited adjusted HRs (aHRs) for mortality below 1, lacking statistical significance. This finding was stable in various sensitivity analyses. Joint aHR for non-TNFi biologics and JAKi versus TNFi was 0.56 (95% CI 0.33 to 0.97). Receiving no DMARD treatment was associated with a twofold higher mortality risk compared with receiving any DMARD treatment, aHR 2.03 (95% CI 1.23 to 3.35). CONCLUSIONS: Inflammatory biomarkers and absence of DMARD treatment were associated with increased risk of mortality in patients with RA-ILD. Non-TNFi bDMARDs may confer enhanced therapeutic benefits in patients with RA-ILD.

Authors: T. Rudi, V. Zietemann, Y. Meissner, A. Zink, A. Krause, H. M. Lorenz, C. Kneitz, M. Schaefer, A. Strangfeld

Date Published: 2024

Publication Type: Journal

Comparative risk of incident malignancies in rheumatoid arthritis patients treated with Janus kinase inhibitors or bDMARDs: observational data from the German RABBIT register

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ABSTRACT Objectives To estimate the effects of Janus kinase inhibitors (JAKis) vs biologic disease-modifying antirheumatic drugs (bDMARDs) on the risk of incident malignancies (excluding nonmelanoma … skin cancer) in patients and patient subgroups with rheumatoid arthritis. Methods Episodes of disease-modifying antirheumatic drug (DMARD) treatment initiated between January 2017 and December 2020 and followed up to June 2024 in RABBIT, the German register for the long-term observation of therapy with biologics and targeted disease-modifying antirheumatic drugs in adult patients with rheumatoid arthritis, were analysed. Incidence rates (IRs) per 1000 patient-years with 95% CIs were calculated, and incident malignancy risk was estimated as hazard ratios (HRs) by inverse probability weighted adjusted Cox models. Results Among 2285 JAKi and 4259 bDMARD treatment episodes, 88 and 135 malignancies occurred, respectively. JAKi treatments were dominated by baricitinib and tofacitinib, while most bDMARD treatments comprised tumour necrosis factor inhibitors. IRs were 11.6 (95% CI: 9.3, 14.3) in JAKi- and 8.9 (95% CI: 7.4, 10.5) in bDMARD-treated groups. The adjusted HR comparing JAKis with bDMARDs was 1.40 (95% CI: 1.09, 1.80). An increase in the malignancy risk for JAKi vs bDMARD treatment could only be observed in treatment episodes lasting longer than 16 months. The risk appeared higher in some subgroups of patients, including those who started treatment aged ≥60 years, patients with ≥3 prior conventional synthetic DMARD treatments, and patients with high disease activity. Conclusions In this German observational cohort study, an overall small increase in malignancy risk for JAKi vs bDMARD treatment was observed, with more pronounced risks in some subgroups of patients. The observed risk should be carefully counterbalanced to the known malignancy risk associated with insufficient disease control.

Authors: Martin Schaefer, Alina Purschke, Vera Zietemann, Tatjana Rudi, Yvette Meissner, Adrian Richter, Sylvia Berger, Karin Rockwitz, Klaus Krüger, Karl Matthias Schneider, Anne C. Regierer, Anja Strangfeld

Date Published: 2025

Publication Type: Journal

Factors associated with treatment satisfaction in patients with rheumatoid arthritis: data from the biological register RABBIT

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OBJECTIVE: To assess satisfaction with the effectiveness and tolerability of treatments in patients with rheumatoid arthritis (RA). METHODS: Patients from the RABBIT register, starting a biological (b) … or targeted synthetic (ts) disease-modifying antirheumatic drug (DMARD), or a conventional synthetic (cs)DMARD treatment after >/=1 csDMARD failure, were included. Treatment satisfaction was measured after 1 year of treatment in four categories and binarised for analysis. Logistic regression models were performed to calculate ORs for factors associated with treatment satisfaction. RESULTS: Data of 10 646 patients (74% women, mean 58 years) were analysed. At baseline, 55% of the patients were satisfied with the efficacy and 68% with the tolerability of their previously given treatments. After 1 year, 85% of the patients were satisfied with treatment effectiveness and 90% with tolerability. Baseline satisfaction (OR 2.98, 95% CI 2.58 to 3.44), seropositivity (OR 1.36, 95% CI 1.17 to 1.57), reduction of DAS28 (OR 1.38, 95% CI 1.31 to 1.46) and pain (OR 1.26, 95% CI 1.22 to 1.31), and the improvement of physical capacity (OR 1.22, 95% CI 1.17 to 1.29) were positively associated with treatment satisfaction at follow-up while glucocorticoids (GCs) >5 mg/day, depression, fibromyalgia, obesity, prior bDMARDs and therapy changes were negatively associated. The impact of GC on satisfaction was dose-dependent, becoming strongest for GC >15 mg (OR 0.24, 95% CI 0.16 to 0.34). A 5 mg/day reduction within 12 months was positively associated with satisfaction regarding efficacy (OR 1.19, 95% CI 1.11 to 1.27) and tolerability (OR 1.11, 95% CI 1.03 to 1.21). CONCLUSION: Most patients were satisfied with their treatment’s effectiveness and tolerability after 1 year of treatment. Tapering GCs was positively associated with the improvement of patients’ satisfaction.

Authors: M. Schafer, K. Albrecht, J. Kekow, K. Rockwitz, A. Liebhaber, A. Zink, A. Strangfeld

Date Published: 2020

Publication Type: Journal

Corrigendum to: Obesity reduces the real-world effectiveness of cytokine-targeted but not cell-targeted disease-modifying agents in rheumatoid arthritis

Abstract

Not specified

Authors: M. Schafer, Y. Meissner, J. Kekow, S. Berger, S. Remstedt, B. Manger, J. Listing, A. Strangfeld, A. Zink

Date Published: 2020

Publication Type: Journal

Obesity reduces the real-world effectiveness of cytokine-targeted but not cell-targeted disease-modifying agents in rheumatoid arthritis

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OBJECTIVES: The effectiveness of TNF inhibitors in RA has been shown to be affected by obesity. No such effect has been found for abatacept and rituximab, while for tocilizumab results are ambiguous. … Additionally, it remains unresolved whether sex is an effect modifier for obesity. We investigated the impact of obesity on the drug effectiveness of conventional synthetic or biologic DMARDs, taking into account potential sex-specific differences. METHODS: Data from 10 593 RA patients included in the German observational cohort study Rheumatoid Arthritis: oBservation of BIologic Therapy (RABBIT) since 2009 were analysed. Patients had to have a BMI >/=18.5 kg/m2, at least one follow-up and 6 months of observation time. The influence of obesity on drug effectiveness was investigated by regression analysis, adjusting for potential confounders. RESULTS: Obesity had a negative impact on improvement in the DAS with 28 joints using ESR as an inflammation marker of -0.15 (95% CI: -0.26; -0.04) units for women receiving conventional synthetic DMARDs, -0.22 (95% CI: -0.31; -0.12) units for women receiving TNF inhibitors, -0.22 (95% CI: -0.42; -0.03) units for women receiving tocilizumab and -0.41 (95% CI: -0.74; -0.07) units for men receiving tocilizumab. Overall, no negative obesity effects on the effectiveness of rituximab and abatacept were found. CONCLUSION: Obesity has a negative impact on the effectiveness of cytokine-targeted but not cell-targeted therapies in daily practice, affecting more outcomes and therapies in women than in men. Overall, no effects of obesity on treatment effectiveness were found for rituximab and abatacept.

Authors: M. Schafer, Y. Meissner, J. Kekow, S. Berger, S. Remstedt, B. Manger, J. Listing, A. Strangfeld, A. Zink

Date Published: 2020

Publication Type: Journal

[Medication treatment of rheumatoid arthritis with a history of malignancy. Epidemiological data]

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INTRODUCTION: Only insufficient data are available regarding the question whether treatment with immunosuppressants or biologicals is feasible and safe in patients with a history of malignancy. METHOD: … Literature search via PubMed, EULAR abstracts and ACR abstracts from 2013 to 2015. RESULTS: The Societe Francaise de Rhumatologie, the Canadian Rheumatology Association and the American College of Rheumatology have tried to make recommendations on this topic. Direct evidence mainly originates from data in three national registries which suggest that treatment with tumor necrosis factor (TNF) inhibitors and rituximab appears to be safe for carefully selected patients, at least if there is a longer interval between treatment with biologicals and oncological treatment. Furthermore, despite partly conflicting data all routine drugs for treating rheumatoid arthritis do not seem to show a consistently increased risk of de novo malignancies. The currently available data are presented for each drug of interest. CONCLUSION: Taking the current literature into account an attempt is made to formulate an algorithm for the medicinal treatment of patients with rheumatoid arthritis and a history of malignancy.

Authors: M. Schmalzing, A. Strangfeld, H. P. Tony

Date Published: 2016

Publication Type: Journal

Abatacept and non-melanoma skin cancer in patients with rheumatoid arthritis: a comprehensive evaluation of randomised controlled trials and observational studies

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OBJECTIVES: This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA). METHODS: This evaluation included 16 abatacept RA clinical … trials and 6 observational studies. NMSC incidence rates (IRs)/1000 patient-years (p-y) of exposure were compared between patients treated with abatacept versus placebo, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biological/targeted synthetic (b/ts)DMARDs. For observational studies, a random-effects model was used to pool rate ratios (RRs). RESULTS:  49 000 patients receiving abatacept were analysed from clinical trials ( 7000) and observational studies ( 42 000). In randomised trials (n=4138; median abatacept exposure, 12 (range 2-30) months), NMSC IRs (95% CIs) were not significantly different for abatacept (6.0 (3.3 to 10.0)) and placebo (4.0 (1.3 to 9.3)) and remained stable throughout the long-term, open-label period (median cumulative exposure, 28 (range 2-130 months); 21 335 p-y of exposure (7044 patients over 3 years)). For registry databases, NMSC IRs/1000 p-y were 5-12 (abatacept), 1.6-10 (csDMARDs) and 3-8 (other b/tsDMARDs). Claims database IRs were 19-22 (abatacept), 15-18 (csDMARDs) and 14-17 (other b/tsDMARDs). Pooled RRs (95% CIs) from observational studies for NMSC in patients receiving abatacept were 1.84 (1.00 to 3.37) vs csDMARDs and 1.11 (0.98 to 1.26) vs other b/tsDMARDs. CONCLUSIONS: Consistent with the warnings and precautions of the abatacept label, this analysis suggests a potential increase in NMSC risk with abatacept use compared with csDMARDs. No significant increase was observed compared with b/tsDMARDs, but the lower limit of the 95% CI was close to unity.

Authors: T. A. Simon, L. Dong, S. Suissa, K. Michaud, S. Pedro, M. Hochberg, M. Boers, J. Askling, T. Frisell, A. Strangfeld, Y. Meissner, V. Khaychuk, A. Dominique, M. A. Maldonado

Date Published: 2024

Publication Type: Journal

Malignancy outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study

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OBJECTIVE: To evaluate the risk of malignancy (overall, breast, lung, and lymphoma) in patients with rheumatoid arthritis treated with abatacept, conventional synthetic (cs) disease-modifying antirheumatic … drugs (DMARDs), and other biologic/targeted synthetic (b/ts)DMARDs in clinical practice. METHODS: Four international observational data sources were included: ARTIS (Sweden), RABBIT (Germany), FORWARD (USA), and BC (Canada). Crude incidence rates (IRs) per 1000 patient-years of exposure with 95% confidence intervals (CIs) for a malignancy event were calculated; rate ratios (RRs) were estimated and adjusted for demographics, comorbidities, and other potential confounders. RRs were then pooled in a random-effects model. RESULTS: Across data sources, mean follow-up for patients treated with abatacept (n = 5182), csDMARDs (n = 73,755), and other b/tsDMARDs (n = 37,195) was 3.0-3.7, 2.9-6.2, and 3.1-4.7 years, respectively. IRs per 1000 patient-years for overall malignancy ranged from 7.6-11.4 (abatacept), 8.6-13.2 (csDMARDs), and 5.0-11.8 (other b/tsDMARDs). IRs ranged from: 0-4.4, 0-3.3, and 0-2.5 (breast cancer); 0.1-2.8, 0-3.7, and 0.2-2.9 (lung cancer); and 0-1.1, 0-0.9, and 0-0.6 (lymphoma), respectively, for the three treatment groups. The numbers of individual cancers (breast, lung, and lymphoma) in some registries were low; RRs were not available. There were a few cases of lymphoma in some of the registries; ARTIS observed an RR of 2.8 (95% CI 1.1-6.8) with abatacept versus csDMARDs. The pooled RRs (95% CIs) for overall malignancy with abatacept were 1.1 (0.8-1.5) versus csDMARDs and 1.0 (0.8-1.3) versus b/tsDMARDs. CONCLUSIONS: This international, post-marketing observational safety study did not find any statistically significant increase in the risk of overall malignancies in pooled data in patients treated with abatacept compared with csDMARDs or with other b/tsDMARDs. Assessment of larger populations is needed to further evaluate the risks for individual cancers, especially lymphoma.

Authors: T. A. Simon, S. Suissa, M. Boers, M. C. Hochberg, M. L. Skovron, J. Askling, K. Michaud, A. Strangfeld, S. Pedro, T. Frisell, Y. Meissner, A. Dominique, A. Gomez

Date Published: 2024

Publication Type: Journal

Infection outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study

Abstract (Expand)

OBJECTIVE: To evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus … conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. METHODS: Five international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). RESULTS: The data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2-6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19-46 for csDMARDs, and 18-40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4-7.8, 0.3-4.3, and 0.5-3.8; IRs for tuberculosis were 0.0-8.4, 0.0-6.0, and 0.0-6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6-2.2) for abatacept versus csDMARDs and 0.9 (0.6-1.3) versus other b/tsDMARDs. CONCLUSIONS: Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.

Authors: T. A. Simon, S. Suissa, M. L. Skovron, T. Frisell, J. Askling, K. Michaud, S. Pedro, A. Strangfeld, Y. Meissner, M. Boers, V. Hoffman, A. Dominique, A. Gomez, M. C. Hochberg

Date Published: 2024

Publication Type: Journal

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update

Abstract (Expand)

OBJECTIVES: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. METHODS: An international task force was formed … and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item. RESULTS: The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations. CONCLUSIONS: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.

Authors: J. S. Smolen, R. B. M. Landewe, S. A. Bergstra, A. Kerschbaumer, A. Sepriano, D. Aletaha, R. Caporali, C. J. Edwards, K. L. Hyrich, J. E. Pope, S. de Souza, T. A. Stamm, T. Takeuchi, P. Verschueren, K. L. Winthrop, A. Balsa, J. M. Bathon, M. H. Buch, G. R. Burmester, F. Buttgereit, M. H. Cardiel, K. Chatzidionysiou, C. Codreanu, M. Cutolo, A. A. den Broeder, K. El Aoufy, A. Finckh, J. E. Fonseca, J. E. Gottenberg, E. A. Haavardsholm, A. Iagnocco, K. Lauper, Z. Li, I. B. McInnes, E. F. Mysler, P. Nash, G. Poor, G. G. Ristic, F. Rivellese, A. Rubbert-Roth, H. Schulze-Koops, N. Stoilov, A. Strangfeld, A. van der Helm-van Mil, E. van Duuren, T. P. M. Vliet Vlieland, R. Westhovens, D. van der Heijde

Date Published: 2023

Publication Type: Journal

EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update

Abstract (Expand)

OBJECTIVES: To provide an update of the European League Against Rheumatism (EULAR) rheumatoid arthritis (RA) management recommendations to account for the most recent developments in the field. METHODS: … An international task force considered new evidence supporting or contradicting previous recommendations and novel therapies and strategic insights based on two systematic literature searches on efficacy and safety of disease-modifying antirheumatic drugs (DMARDs) since the last update (2016) until 2019. A predefined voting process was applied, current levels of evidence and strengths of recommendation were assigned and participants ultimately voted independently on their level of agreement with each of the items. RESULTS: The task force agreed on 5 overarching principles and 12 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); glucocorticoids (GCs); biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab), abatacept, rituximab, tocilizumab, sarilumab and biosimilar (bs) DMARDs) and targeted synthetic (ts) DMARDs (the Janus kinase (JAK) inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib). Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering on sustained clinical remission is provided. Cost and sequencing of b/tsDMARDs are addressed. Initially, MTX plus GCs and upon insufficient response to this therapy within 3 to 6 months, stratification according to risk factors is recommended. With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD or JAK inhibitor should be added to the csDMARD. If this fails, any other bDMARD (from another or the same class) or tsDMARD is recommended. On sustained remission, DMARDs may be tapered, but not be stopped. Levels of evidence and levels of agreement were mostly high. CONCLUSIONS: These updated EULAR recommendations provide consensus on the management of RA with respect to benefit, safety, preferences and cost.

Authors: J. S. Smolen, R. B. M. Landewe, J. W. J. Bijlsma, G. R. Burmester, M. Dougados, A. Kerschbaumer, I. B. McInnes, A. Sepriano, R. F. van Vollenhoven, M. de Wit, D. Aletaha, M. Aringer, J. Askling, A. Balsa, M. Boers, A. A. den Broeder, M. H. Buch, F. Buttgereit, R. Caporali, M. H. Cardiel, D. De Cock, C. Codreanu, M. Cutolo, C. J. Edwards, Y. van Eijk-Hustings, P. Emery, A. Finckh, L. Gossec, J. E. Gottenberg, M. L. Hetland, T. W. J. Huizinga, M. Koloumas, Z. Li, X. Mariette, U. Muller-Ladner, E. F. Mysler, J. A. P. da Silva, G. Poor, J. E. Pope, A. Rubbert-Roth, A. Ruyssen-Witrand, K. G. Saag, A. Strangfeld, T. Takeuchi, M. Voshaar, R. Westhovens, D. van der Heijde

Date Published: 2020

Publication Type: Journal

Updated recommendations of the German Society for Rheumatology for the care of patients with inflammatory rheumatic diseases in the context of the SARS-CoV-2/COVID-19 pandemic, including recommendations for COVID-19 vaccination

Abstract

Not specified

Authors: C. Specker, P. Aries, J. Braun, G. Burmester, R. Fischer-Betz, R. Hasseli, J. Holle, B. F. Hoyer, C. Iking-Konert, A. Krause, K. Kruger, M. Krusche, J. Leipe, H. M. Lorenz, F. Moosig, R. Schmale-Grede, M. Schneider, A. Strangfeld, R. Voll, A. Voormann, U. Wagner, H. Schulze-Koops

Date Published: 2021

Publication Type: Journal

[Updated recommendations of the German Society for Rheumatology for the care of patients with inflammatory rheumatic diseases in the context of the SARS-CoV‑2/COVID‑19 pandemic, including recommendations for COVID‑19 vaccination]

Abstract

Not specified

Authors: C. Specker, P. Aries, J. Braun, G. Burmester, R. Fischer-Betz, R. Hasseli, J. Holle, B. F. Hoyer, C. Iking-Konert, A. Krause, K. Kruger, M. Krusche, J. Leipe, H. M. Lorenz, F. Moosig, R. Schmale-Grede, M. Schneider, A. Strangfeld, R. Voll, A. Voormann, U. Wagner, H. Schulze-Koops

Date Published: 2021

Publication Type: Journal

[Not Available]

Abstract

Not specified

Author: A. Strangfeld

Date Published: 2015

Publication Type: Journal

[Sepsis and mortality after severe infections : How epidemiological data confirm results of animal experiments]

Abstract

Not specified

Author: A. Strangfeld

Date Published: 2017

Publication Type: Journal

[Celebrating 33 years of the DRFZ: Epidemiology and Health Services Research]

Abstract (Expand)

The scientific focus of the DRFZ’s Programme Area Epidemiology and Health Services Research is, on the one hand, investigating the health care situation of people with rheumatic diseases in Germany, … including its deficits, progress and trends. On the other hand, an essential goal is to uncover risk factors for unfavourable disease trajectories, but also protective factors, through the long-term observation of disease courses in large cohorts. With the approval of innovative, targeted therapies at the beginning of this millennium, the question of the real-world safety and effectiveness of the various anti-rheumatic therapies became a key issue for doctors and patients. The biologics registers have developed into central instruments of the programme area, which enable questions on comparative drug safety, but also on therapy effectiveness and risk reduction through effective therapy, to be answered in a robust manner.In this article, selected results of epidemiological research at the DRFZ are presented. The overall goal of the research was and is to contribute to improving the quality of life of children and adults with rheumatic and musculoskeletal diseases. This is the purpose of clinical-evaluative health services research as well as the acquisition of knowledge that supports effective, individualised therapy. Large, long-term patient cohorts and a stable network with clinical rheumatologists and those affected have proven to be indispensable instruments.

Authors: A. Strangfeld, K. Albrecht, A. Regierer, J. Callhoff, A. Zink, K. Minden

Date Published: 2022

Publication Type: Journal

Methotrexate: what are the true risks of treatment?

Abstract

Not specified

Authors: A. Strangfeld, G. R. Burmester

Date Published: 2020

Publication Type: Journal

Treatment benefit or survival of the fittest: what drives the time-dependent decrease in serious infection rates under TNF inhibition and what does this imply for the individual patient?

Abstract (Expand)

OBJECTIVE: To examine the risk of serious infection conveyed by tumour necrosis factor alpha (TNFalpha) inhibitors in the treatment of rheumatoid arthritis (RA). METHODS: Data from patients with RA … enrolled in the German biologics register RABBIT were used for analysis. Baseline patient characteristics, time-varying risk factors (treatment changes, functional capacity) and selection processes caused by dropout, death or switching to non-anti-TNF treatment were taken into account to estimate the adjusted incidence rate ratios (IRR(adj)) of serious infection during treatment with TNF inhibitors compared with non-biological disease-modifying antirheumatic drug treatment. RESULTS: Data were available on 5044 patients, in whom 392 serious infections occurred. The crude rates of serious infections in patients treated with TNF inhibitors declined over the first 3 years of observation (from 4.8 to 2.2/100 patient-years). This decline was driven by (1) treatment termination or loss to follow-up in patients at increased risk and (2) a risk reduction through decreasing glucocorticoid doses and improvement in function. Adjusted for selection processes and time-varying risk factors, the following parameters assessed at baseline (age, chronic diseases) or at follow-up prior to the infection were significantly associated with an increased risk: age >60 years, chronic lung or renal disease, low functional capacity, history of serious infections, treatment with glucocorticoids (7.5-14 mg/day, IRR(adj) 2.1 (95% CI 1.4 to 3.2); >/= 15 mg/day, IRR(adj) 4.7 (95% CI 2.4 to 9.4)) and treatment with TNFalpha inhibitors (IRR(adj) 1.8 (95% CI 1.2 to 2.7)). CONCLUSION: Reasons for the decline in infection rates observed at the group level were identified. The results enable expected infection rates to be calculated in individual patients based on their risk profiles.

Authors: A. Strangfeld, M. Eveslage, M. Schneider, H. J. Bergerhausen, T. Klopsch, A. Zink, J. Listing

Date Published: 2011

Publication Type: Journal

Comparative effectiveness of tumour necrosis factor alpha inhibitors in combination with either methotrexate or leflunomide

Abstract (Expand)

OBJECTIVE: The objective of this study was to compare the effectiveness of a combination of tumour necrosis factor alpha (TNFalpha) inhibitors with either methotrexate or leflunomide in the treatment … of patients with rheumatoid arthritis in a real-world setting. METHODS: Data from 1769 outpatients enrolled in the German biologics register RABBIT who were treated with one of the TNFalpha inhibitors adalimumab, etanercept, or infliximab in combination with either methotrexate (n = 1375) or leflunomide (n = 394) were included in the analysis. Clinical status including disease activity as well as treatment data were documented by the treating rheumatologist at baseline and at 3, 6, 12, 18, 24, 30 and 36 months of follow-up. RESULTS: Patients treated with a combination of biologics with leflunomide had significantly higher baseline disease activity than those treated with methotrexate. The highest disease activity was found for patients treated with the combination infliximab/leflunomide. After 36 months, the discontinuation rates were 46.3%, 51.3% and 61.5% for combinations of etanercept, adalimumab and infliximab with methotrexate and 53.4%, 63.1% and 67.1% for combinations with leflunomide, respectively. European League Against Rheumatism response rates after 24 months ranged from 74% to 81% for combinations with methotrexate and 72% to 81% for combinations with leflunomide. CONCLUSION: The current clinical practice is to use methotrexate as a first choice for the combination with TNFalpha antagonists. In a number of patients methotrexate has to be replaced by another disease-modifying antirheumatic drug. Our data support the view that leflunomide is a useful alternative if methotrexate is contraindicated.

Authors: A. Strangfeld, F. Hierse, J. Kekow, U. von Hinueber, H. P. Tony, R. Dockhorn, J. Listing, A. Zink

Date Published: 2009

Publication Type: Journal

Risk of incident or recurrent malignancies among patients with rheumatoid arthritis exposed to biologic therapy in the German biologics register RABBIT

Abstract (Expand)

INTRODUCTION: We used the data of the German biologics register RABBIT, a nationwide prospective cohort study, to investigate the risk of new or recurrent malignancy in patients with rheumatoid arthritis … (RA) receiving biologics compared to conventional disease modifying anti-rheumatic drugs (DMARDs). METHODS: The analysis was based on patients with RA enrolled in RABBIT at the start of a biologic or conventional DMARD therapy between 01 May 2001 and 31 December 2006. Incidences of first or recurrent malignancies were analysed separately. A nested case-control design was used to investigate the risk of developing a first malignancy. Matching criteria were: age, gender, follow-up time, disease activity score based on 28 joint counts (DAS28) at study entry, smoking status, and selected chronic co-morbid conditions (obstructive or other lung disease, kidney, liver or gastrointestinal disease, psoriasis). RESULTS: A prior malignancy was reported in 122 out of 5,120 patients. Fifty-eight of these patients had received anti-TNFalpha agents, 9 anakinra, and 55 conventional DMARDs at study entry. In 14 patients (ever exposed to anti-TNFalpha: eight, to anakinra: one) 15 recurrent cancers were observed. The average time period since the onset of the first malignancy was nine years. Crude recurrence rates per 1,000 patient-years (pyrs) were 45.5 for patients exposed to anti-TNFalpha agents, 32.3 for anakinra patients and 31.4 for patients exposed to DMARDs only (Incidence rate ratio anti-TNFalpha vs. DMARD = 1.4, P = 0.6.). In patients without prior cancer, 74 patients (70% female, mean age: 61.3) developed a first malignancy during the observation. This corresponds to an incidence rate (IR) of 6.0/1,000 pyrs. Forty-four of these patients were ever exposed to anti-TNFalpha treatment (IR = 5.1/1,000 pyrs). In a nested case-control study comparing cancer patients to cancer-free controls, 44 of the cancer patients and 44 of the cancer-free controls were ever exposed to anti-TNFalpha agents (P = 1.0). CONCLUSIONS: No significant differences in the overall incidence of malignancies in patients exposed or unexposed to anti-TNFalpha or anakinra treatment were found. The same applied to the risk of recurrent malignancies. However, in particular this last finding needs further validation in larger data sets.

Authors: A. Strangfeld, F. Hierse, R. Rau, G. R. Burmester, B. Krummel-Lorenz, W. Demary, J. Listing, A. Zink

Date Published: 2010

Publication Type: Journal

Detection and evaluation of a drug safety signal concerning pancreatic cancer: lessons from a joint approach of three European biologics registers

Abstract (Expand)

OBJECTIVES: A high incidence of pancreatic cancer (PCa) in patients exposed to was observed in the German biologics register. To evaluate this possible safety signal, a concerted analysis with the … national biologics registers in the UK and Sweden was performed. METHODS: Patients with enrolled in the British Society of Rheumatology Biologics Register (BSRBR), the Swedish Rheumatology Register (SRR) or the German Biologics Register [Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT)] were analysed. The patients were exposed to biologic or conventional DMARDs. Outcomes were obtained from physician reports, health authorities and via linkage to national cancer and death registers. Age- and gender-standardized incidence ratios (SIRs) of PCa were calculated based on the expected rates available from the individual national cancer registers. RESULTS: Data from 5126 (Germany), 16 930 (UK) and 19 351 (Sweden) RA patients were available for the analysis. The highly discrepant prescription rates of LEF in the respective countries resulted in 11 343 (Germany), 30 787 (UK) and 2518 (S) patient-years of exposure to LEF. Compared with the general population, the incidence of PCa in patients ever exposed to LEF corresponded to a SIR of 3.1 (95% CI 1.3, 6.5) in Germany, 1.05 (95% CI 0.5, 2.1) in the UK and 1.8 (95% CI 0.1, 10.2) in Sweden. CONCLUSION: The results of the replication analyses do not support the hypothesis of an increased risk of PCa in patients exposed to treatment with LEF. However, they do not completely rule out concerns, and therefore further verification in other data sets is recommended.

Authors: A. Strangfeld, K. Hyrich, J. Askling, E. Arkema, R. Davies, J. Listing, M. Neovius, J. Simard, D. Symmons, K. Watson, A. Zink

Date Published: 2011

Publication Type: Journal

Risk of herpes zoster in patients with rheumatoid arthritis treated with anti-TNF-alpha agents

Abstract (Expand)

CONTEXT: The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor alpha (TNF-alpha). Little is known about the reactivation of latent viral infections … during treatment with TNF-alpha inhibitors. OBJECTIVE: To investigate whether TNF-alpha inhibitors together as a class, or separately as either monoclonal anti-TNF-alpha antibodies (adalimumab, infliximab) or a fusion protein (etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis. DESIGN, SETTING, AND PATIENTS: Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease-modifying antirheumatic drug (DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow-up. MAIN OUTCOME MEASURES: Hazard ratio (HR) of herpes zoster episodes following anti-TNF-alpha treatment. Study aims were to detect a clinically significant difference (HR, 2.0) between TNF-alpha inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF-alpha inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs. RESULTS: Among 5040 patients receiving TNF-alpha inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty-nine occurrences could be attributed to treatment with anti-TNF-alpha antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient-years was 11.1 (95% confidence interval [CI], 7.9-15.1) for the monoclonal antibodies, 8.9 (95% CI, 5.6-13.3) for etanercept, and 5.6 (95% CI, 3.6-8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies (HR, 1.82 [95% CI, 1.05-3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use (HR, 1.36 [95% CI, 0.73-2.55]) or for anti-TNF-alpha treatment (HR, 1.63 [95% CI, 0.97-2.74]) as a class. CONCLUSION: Treatment with monoclonal anti-TNF-alpha antibodies may be associated with increased risk of herpes zoster, but this requires further study.

Authors: A. Strangfeld, J. Listing, P. Herzer, A. Liebhaber, K. Rockwitz, C. Richter, A. Zink

Date Published: 2009

Publication Type: Journal

[How do register data support clinical decision-making?]

Abstract (Expand)

BACKGROUND: Patients in daily rheumatological care differ in their individual risk profiles from participants in randomized controlled trials (RCT), e.g. due to comorbidities and age. Transferring … results from RCTs into routine daily practice is therefore limited. OBJECTIVE: The aim of this study was to evaluate the contribution of observational studies for decision-making in routine rheumatology practice. MATERIAL AND METHODS: We used data from the German biologics register RABBIT which includes patients with rheumatoid arthritis (RA) when starting synthetic (s) or biologic (b) disease-modifying antirheumatic drugs (DMARD). They are observed for at least 5 years. Comorbidities and clinically relevant aspects (e.g. history of malignancies) are reported at baseline and adverse events at regular follow-up. RESULTS: Only one out of three patients treated with bDMARDs in RABBIT would have fulfilled the inclusion criteria of the respective pivotal study. Register data enabled developing a risk scoring model which evaluates the individual risk of a patient for serious infections depending on different risk factors and the respective DMARD treatment. Open online access to the score provides the possibility of risk estimation for all rheumatologists. Further results identified long-standing high disease activity as a dominant risk factor for a worsening of prevalent comorbidities. In patients with heart failure it was shown that effective treatment and control of disease activity with tumor necrosis factor (TNF) inhibitors was more likely to be protective than harmful. CONCLUSION: Observational studies contribute essentially to the assessment of individual risks of patients. The results provide valuable information to support clinical decision-making and therefore strengthen the evidence when treating patients of higher age or with existing comorbidities.

Authors: A. Strangfeld, A. Richter

Date Published: 2015

Publication Type: Journal

Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs

Abstract (Expand)

OBJECTIVE: To investigate the risk of developing lower intestinal perforations (LIPs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ). METHODS: In 13 310 patients with RA … observed in the German biologics register Rheumatoid Arthritis: Observation of Biologic Therapy, 141 serious gastrointestinal events possibly associated with perforations were reported until 31 October 2015. All events were validated independently by two physicians, blinded for treatment exposure. RESULTS: 37 LIPs (32 in the colon/sigma) were observed in 53 972 patient years (PYs). Only two patients had a history of diverticulitis (one in TCZ). Age, current/cumulative glucocorticoids and non-steroidal anti-inflammatory drugs were significantly associated with the risk of LIP. The crude incidence rate of LIP was significantly increased in TCZ (2.7/1000 PYs) as compared with all other treatments (0.2-0.6/1000 PYs). The adjusted HR (ref: conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs)) in TCZ was 4.48 (95% CI 2.0 to 10.0), in tumour necrosis factor-alpha inhibitor (TNFi) 1.04 (0.5 to 2.3) and in other biologic DMARDs 0.33 (0.1 to 1.4). 4/11 patients treated with TCZ presented without typical symptoms of LIP (acute abdomen, severe pain). Only one patient had highly elevated C reactive protein (CRP). One quarter of patients died within 30 days after LIP (9/37), 5/11 under TCZ, 2/13 under TNFi and 2/11 under csDMARD treatment. CONCLUSIONS: The incidence rates of LIP under TCZ found in this real world study are in line with those seen in randomised controlled trials of TCZ and higher than in all other DMARD treatments. To ensure safe use of TCZ in daily practice, physicians and patients should be aware that, under TCZ, LIP may occur with mild symptoms only and without CRP elevation.

Authors: A. Strangfeld, A. Richter, B. Siegmund, P. Herzer, K. Rockwitz, W. Demary, M. Aringer, Y. Meissner, A. Zink, J. Listing

Date Published: 2017

Publication Type: Journal

Compact plug and play optical frequency reference device based on Doppler-free spectroscopy of rubidium vapor

Abstract (Expand)

Compactness, robustness and autonomy of optical frequency references are prerequisites for reliable operation in mobile systems, on ground as well as in space. We present a standalone plug and play … optical frequency reference device based on frequency modulation spectroscopy of the D2-transition in rubidium at 780 nm. After a single button press the hand-sized laser module, based on the micro-integrated laser-optical bench described in [J. Opt. Soc. Am. B38, 1885 (2021)10.1364/JOSAB.420875], works fully autonomous and generates 6 mW of frequency stabilized light with a relative frequency instability of 1.4x10(-12) at 1 s and below 10(-11) at 10(5) s averaging time. We describe the design of the device, investigate the thermal characteristics affecting the output frequency and demonstrate short-term frequency stability improvement by a Bayesian optimizer varying the modulation parameters.

Authors: A. Strangfeld, B. Wiegand, J. Kluge, M. Schoch, M. Krutzik

Date Published: 2022

Publication Type: Journal

[Safety of biologic therapy - results from the German biologics register RABBIT]

Abstract

Not specified

Authors: A. Strangfeld, A. Zink

Date Published: 2014

Publication Type: Journal

[Influence of therapy on risk of cancer in rheumatoid arthritis. Pathophysiological principles]

Abstract (Expand)

The increased incidence of certain tumor entities in chronic inflammation and infections as well as the increased tumor risk under immunosuppression, illustrate the multiple and complex influences of … the immune system on tumor pathogenesis. It is therefore conceivable that immunomodulatory therapy for rheumatoid arthritis (RA) could also influence the risk of malignancies, apart from treating the underlying disease. Basic scientific research studies have identified various signal transduction pathways that are relevant for tumorigenesis and tumor defense mechanisms. This review presents the current knowledge on the effects of the immune system on the occurrence of cancer and tries, where possible, to relate it to specific treatment options.

Authors: M. J. Waldner, A. Strangfeld, M. Aringer

Date Published: 2016

Publication Type: Journal

[Dose adjustment in patients treated with infliximab in routine rheumatologic care in Germany. Results from the Biologics Register RABBIT]

Abstract (Expand)

OBJECTIVE: Data from international observational studies show that a considerable proportion of patients use higher dosages of infliximab (INF) than the usual 3 mg every 8 weeks used in Germany for … treatment of rheumatoid arthritis. The Data are, however, inconsistent and vary between countries. Using data from the German Biologics Register RABBIT we investigated: (1) how dosage of INF develops during the first year of treatment in routine care, and (2) how dosage translates into clinical effectiveness. PATIENTS: We analysed data from 344 patients who started a treatment with INF at their inclusion into the register and who were observed for the subsequent 12 months. Mean dosage at 3 months (after the loading dose) was 3.2 mg/kg body weight/infusion and 3.3 mg/kg after 1 year. If we also consider shortening the infusion intervals, the mean dosages at the start and after 1 year were 4.0 mg/kg body weight every 8 weeks. RESULTS: Patients who were treated with low dosages of up to 3 mg/kg/8 weeks showed significantly less improvement (EULAR response) than those who were treated with higher dosages. CONCLUSIONS: The data show that German rheumatologists are aware of the high costs of treatment and try to use the lowest possible dosage. However, for a certain proportion of the patients this might be insufficient.

Authors: A. Zink, J. Listing, A. Strangfeld, E. Gromnica-Ihle, W. Demary, M. Schneider

Date Published: 2006

Publication Type: Journal

Evaluation of the RABBIT Risk Score for serious infections

Abstract (Expand)

OBJECTIVE: To evaluate the Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT) Risk Score for serious infections in patients with rheumatoid arthritis (RA). METHODS: The RABBIT Risk Score for … serious infections was developed in 2011 on a cohort of RA patients enrolled in the German biologics register RABBIT between 2001 and 2007. To evaluate this score, we used data from patients enrolled in RABBIT after 1 January 2009. Expected numbers of serious infections and expected numbers of patients with at least one serious infection per year were calculated by means of the RABBIT Risk Score and compared with observed numbers in the evaluation sample. RESULTS: The evaluation of the score in an independent cohort of 1522 RA patients treated with tumour necrosis factor alpha (TNFalpha) inhibitors and 1468 patients treated with non-biological disease-modifying antirheumatic drugs (DMARDs) showed excellent agreement between observed and expected rates of serious infections. For patients exposed to TNF inhibitors, expected as well as observed numbers of serious infections were 3.0 per 100 patient-years (PY). For patients on non-biological DMARDs the expected and observed numbers were 1.5/100 PY and 1.8/100 PY, respectively. The score was highly predictive in groups of patients with low as well as with high infection risk. CONCLUSIONS: The RABBIT Risk Score is a reliable instrument which determines the risk of serious infection in individual patients based on clinical and treatment information. It helps the rheumatologist to balance benefits and risks of treatment, to avoid high-risk treatment combinations and thus to make informed clinical decisions.

Authors: A. Zink, B. Manger, J. Kaufmann, C. Eisterhues, A. Krause, J. Listing, A. Strangfeld

Date Published: 2014

Publication Type: Journal

Effectiveness of tumor necrosis factor inhibitors in rheumatoid arthritis in an observational cohort study: comparison of patients according to their eligibility for major randomized clinical trials

Abstract (Expand)

OBJECTIVE: Randomized clinical trials (RCTs) evaluate the efficacy of treatments in selected groups of patients defined by strict inclusion criteria. The value of these trials in predicting therapeutic … effectiveness in "real world" patients is limited. This observational cohort study was designed to complement the knowledge obtained in RCTs by evaluating the effectiveness of tumor necrosis factor (TNF) inhibitors in patients with rheumatoid arthritis (RA) according to their eligibility for the major trials. METHODS: Using the data from the German biologics register Rheumatoid Arthritis Observation of Biologic Therapy (RABBIT [in German]), we investigated how many of the RA patients who were treated with a TNF inhibitor (infliximab, etanercept, or adalimumab) would have been eligible for the major clinical trials that led to approval of the drugs. In addition, therapeutic effectiveness was compared in the eligible and ineligible patients using the American College of Rheumatology 20% (ACR20) and 50% (ACR50) improvement response criteria. RESULTS: Only 21-33% of the patients in the RABBIT register would have been eligible for the major trials. In these patients, the ACR20 and ACR50 improvement responses, indicating therapeutic effectiveness, were comparable with the response rates in the published trials. ACR response rates were lower in those patients considered ineligible for the trials; however, absolute improvement was similar to that in eligible patients. Ineligible patients had lower baseline disease activity, more comorbidity, and lower functional status. CONCLUSION: RCT cohorts reflect only a minor proportion of the patients treated with biologic agents in routine care. In the clinic setting, the indications for treatment with biologic agents are not identical to the inclusion criteria for trials. Despite the smaller relative improvement achieved in these patients with longstanding, severe RA who would not fulfill the inclusion criteria of a major trial, the majority of such patients would nevertheless benefit from biologic therapy.

Authors: A. Zink, A. Strangfeld, M. Schneider, P. Herzer, F. Hierse, M. Stoyanova-Scholz, S. Wassenberg, A. Kapelle, J. Listing

Date Published: 2006

Publication Type: Journal

Trends in work participation among patients with inflammatory rheumatic musculoskeletal diseases (iRMDs): Data from the German National Database (2010-2022).

Abstract (Expand)

OBJECTIVE: To analyse work participation among patients with inflammatory rheumatic musculoskeletal diseases (iRMDs), namely rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis … (PsA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ANCA-associated vasculitis (AAV). METHODS: A cross-sectional sample of 16 421 patients from the National Database of the German Collaborative Arthritis Centers, aged <65 years were analysed. For each diagnosis, yearly rates of absenteeism, employment and disability pensions were analysed from 2010 to 2022. Population data were used to calculate standardised employment ratios (SERs), adjusted for age, sex, federal state and vocational qualification. The analysis was additionally stratified by sex, adjusting for other factors. RESULTS: Over the observed time span, large employment increases were found across all diagnoses, namely in RA (54%-68%), PsA (58%-72%), SSc (47%-66%), AAV (43%-61%), SLE (48%-60%) and axSpA (65%-73%). SERs were for RA 0.88 (95% CI 0.86 to 0.90), axSpA (0.88 (0.84 to 0.91)), PsA (0.88 (0.85 to 0.91)), SSc (0.83 (0.75 to 0.91)), SLE (0.76 (0.72 to 0.80)) and AAV (0.73 (0.63 to 0.83)). In RA, axSpA, PsA and AAV, SERs were higher in men while in SLE and SSc men had lower SER. Median of yearly absenteeism due to the disease decreased by 5 (RA), 1 (axSpA), 6 (PsA), 11 (SLE), 4 (SSc) and 10 days (AAV) in the time span. Except for SSc, the proportion of disability pension receivers decreased for all diagnoses. CONCLUSION: Since 2010, work participation has improved for patients with iRMDs, as reflected in higher employment, reduced absenteeism and less disability retirement. However, patients have not reached population employment rates.

Authors: C. Veltri, K. Albrecht, U. Kiltz, D. Meyer-Olson, S. Spathling, A. Strangfeld, K. Thiele, J. Callhoff

Date Published: 25th Jan 2025

Publication Type: Journal

[Current data on rheumatological care: annual report from the National database (NDB) of the regional collaborative arthritis centres in Germany].

Abstract (Expand)

In the National database (NDB) of the German regional collaborative arthritis centres, annual data on the rheumatological care of patients with inflammatory rheumatic diseases have been collected since … 1993. This first annual report presents current cross-sectional data on medication and patient-reported outcomes gathered in 2022.

Authors: K. Albrecht, K. Thiele, T. Alexander, M. Aringer, T. Eidner, J. Henes, G. Hoese, K. Karberg, U. Kiltz, A. Krause, W. Ochs, J. G. Richter, S. Spathling-Mestekemper, M. Steinmuller, S. Wassenberg, A. Strangfeld, J. Callhoff

Date Published: 16th Oct 2024

Publication Type: Journal

Recording of non-musculoskeletal manifestations, comorbidities and safety outcomes in European spondyloarthritis registries: a survey

Abstract (Expand)

OBJECTIVES: Real-world evidence is needed to inform treatment strategies for patients with PsA and axial SpA (axSpA) who have non-musculoskeletal manifestations (NMMs), various risk factors and … comorbidities. International collaboration is required to ensure statistical power and to enhance generalizability. The first step forward is identifying which data are currently being collected. Across 17 registries participating in the European Spondyloarthritis Research Collaboration (EuroSpA), we aimed to map recording practices for NMMs, comorbidities and safety outcomes in patients with PsA and axSpA. METHODS: Through a survey with 4,420 questionnaire items, we explored the recording practices of 58 pre-defined conditions (i.e. NMMs, comorbidities and safety outcomes) covering 10 disease areas. In all registries we mapped for each condition whether it was recorded, the recording procedure and the potential to identify it through linkage to other national registries. RESULTS: Conditions were generally recorded at entry into the registry and clinical follow-up visits using a pre-specified list or a coding system. Most registries recorded conditions within the following disease areas: NMMs (number of registries, n = 15-16), cardiovascular diseases (n = 10-14), gastrointestinal diseases (n = 12-13), infections (n = 10-13) and death (n = 14). Nordic countries had the potential for data linkage and generally had limited recording of conditions in their registry, while other countries had comprehensive recording practices. CONCLUSION: A wide range of conditions were consistently recorded across the registries. The recording practices of many conditions and disease areas were comparable across the registries. Our findings support the potential for future collaborative research.

Authors: Z. F. Ahmadzay, J. Heberg, J. B. Jørgensen, L. M. Ørnbjerg, M. Østergaard, S. Møller-Bisgaard, B. Michelsen, A. G. Loft, G. T. Jones, P. Hellamand, A. Scherer, M. J. Nissen, K. Pavelka, J. Závada, K. Laas, S. Vorobjov, D. Nordström, T. Sokka-Isler, A. C. Regierer, A. Reich, B. Gudbjornsson, K. Thorarinsdottir, F. Iannone, E. G. Favalli, M. van de Sande, S. A. Provan, T. K. Kvien, A. M. Rodrigues, C. F. Gonçalves, C. Codreanu, C. Mogosan, Z. Rotar, K. P. Prikmajer, I. Castrejon, L. Otero-Varela, D. Di Giuseppe, J. K. Wallman, A. Ciurea, B. Möller, G. Kenar-Artın, T. D. Yıldırım, G. J. Macfarlane, O. Rotariu, B. Glintborg, M. L. Hetland

Date Published: 2024

Publication Type: Journal

Characterization of patients with psoriatic arthritis in dermatologic and rheumatologic care: analysis of two registries

Abstract (Expand)

Summary Background and objective Psoriatic arthritis (PsA) is a chronic systemic inflammatory disease affecting the musculoskeletal system, skin and nails. The aim is to characterize sociodemographic … and clinical patient profiles documented in dermatologic and rheumatologic care. Patients and Methods Data of 704 patients with PsA from the dermatological Psoriasis Registry PsoBest (PB) and 1066 patients from the rheumatological disease registry RABBIT-SpA (RS) were analyzed. Comparable anamnestic and clinical variables were identified and descriptively analyzed. Results The mean age was 51.7 years in PB and 51.9 in RS. Disease duration of psoriasis was longer, mean cutaneous severity was higher in PB. However, more patients in RS vs. PB had tender joints and swollen joints. Mean Dermatology Life Quality Index was higher in PB and mean Health Assessment Questionnaire in RS. Patient reported global disease activity and pain were lower in PB. IL-23 inhibitors were used more frequently in PB, and TNF inhibitors in RS. Conclusions Clinical specialization was associated with different clinical and treatment patterns of PsA. This may indicate a selection by dominant manifestation of psoriatic disease and potentially by effects of health care access. Psoriatic arthritis should be treated in a multidisciplinary approach considering all facets of this complex disease.

Authors: Matthias Augustin, Lisa Lindner, Laura Kühl, Anja Weiss, Stephan Jeff Rustenbach, Brigitte Stephan, Martin Feuchtenberger, Ulrich Mrowietz, Diamant Thaçi, Petra Staubach, Xenofon Baraliakos, Anja Strangfeld, Ralph von Kiedrowski, Frank Behrens, Anne Constanze Regierer

Date Published: 2023

Publication Type: Journal

Implementing an automated monitoring process in a digital, longitudinal observational cohort study

Abstract (Expand)

Clinical data collection requires correct and complete data sets in order to perform correct statistical analysis and draw valid conclusions. While in randomized clinical trials much effort concentrates … on data monitoring, this is rarely the case in observational studies- due to high numbers of cases and often-restricted resources. We have developed a valid and cost-effective monitoring tool, which can substantially contribute to an increased data quality in observational research.

Authors: Lisa Lindner, Anja Weiß, Andreas Reich, Siegfried Kindler, Frank Behrens, Jürgen Braun, Joachim Listing, Georg Schett, Joachim Sieper, Anja Strangfeld, Anne C. Regierer

Date Published: 2021

Publication Type: Journal

No difference in clinical parameters and drug retention in PsA patients receiving b/tsDMARD monotherapy versus combination with methotrexate: data from the RABBIT-SpA registry

Abstract (Expand)

BACKGROUND: The potential benefit of methotrexate (MTX) in combination with biologic (b) and targeted synthetic (ts) disease modifying anti-rheumatic drugs (DMARDs) in psoriatic arthritis (PsA) is still … a matter of debate. OBJECTIVES: To compare clinical and patient reported characteristics as well as drug retention rates in PsA patients receiving b/tsDMARD monotherapy or in combination with MTX. METHODS: RABBIT-SpA is a prospective longitudinal cohort study including axSpA and PsA patients. In this analysis, PsA patients were stratified into two groups: starting b/tsDMARD as monotherapy or in combination with MTX. Treatment retention was compared by drug survival analysis. RESULTS: 69% of the patients (n=900) started b/tsDMARD as monotherapy while 31% were treated in combination with MTX (n=405). At baseline, clinical domains like skin, nail and joint affection, dactylitis, enthesitis and axial involvement were similar between the groups. Only the patients’ satisfaction concerning tolerability of the previous treatment was significantly better in the combination group at treatment start. Drug retention rates did not differ between the groups (p=0.4). At 6/12 months, 66%/48% of patients in monotherapy and 67%/48% in the combination group were still on their original treatment. CONCLUSIONS: We did not identify any clinical parameters with notable influence on the choice of b/tsDMARD mono or MTX-combination therapy in PsA. Drug retention rates are similar between mono and combination therapy. It seems that the decision to continue MTX at initiation of b/tsDMARDs is mostly based on the subjective tolerability of MTX treatment.

Authors: A. C. Regierer, D. Kiefer, G. Schett, A. Krause, A. Weiss, P. Sewerin, A. Strangfeld

Date Published: 2024

Publication Type: Journal

Integration of a medication reminder app into the RABBIT-SpA disease registry to record patient data on daily drug usage

Abstract

Not specified

Authors: Anne C. Regierer, Andreas Reich, Anja Weiß, Martin Feuchtenberger, Silke Zinke, Hanns-Martin Lorenz, Uta Syrbe, Peter Böhm, Julius Wiegand, Anja Strangfeld

Date Published: 2025

Publication Type: Journal

RABBIT-SpA – nationale Registerdaten zu Spondyloarthritiden

Abstract (Expand)

Seit 2017 wird im Deutschen Rheuma-Forschungszentrum das Krankheitsregister RABBIT-SpA für die axiale Spondyloarthritis und die Psoriasis-Arthritis durchgeführt. Fast 80 rheumatologische Einrichtungen … in ganz Deutschland sind aktiv beteiligt. Es liegen inzwischen Daten von je über 1.800 Patient:innen für beide Erkrankungen vor. Da die Patient:innen zu Beginn einer neuen Therapie eingeschlossen werden, ist die Krankheitsaktivität im Vergleich zu anderen Kohorten aus dem Versorgungsalltag relativ hoch. Es wurden bereits einige Analysen der RABBIT-SpA-Patient:innen publiziert. Es konnte zum Beispiel gezeigt werden, dass die Therapieretention bei PsA-Patient:innen, die entweder mit einer b/tsDMARD-Monotherapie oder einer Kombination eines b/tsDMARDs mit MTX behandelt wurden, gleich war. Eine Analyse zur mentalen Gesundheit zeigte, dass bei ca. 30% der Patient:innen depressive Symptome vorliegen, sowohl bei der axSpA als auch bei der PsA. In einer weiteren Analyse wurden PsA-Patient:innen, die auch eine axiale Beteiligung haben mit den axSpA-Patient:innen, die auch eine Hautpsoriasis haben, verglichen. axPsA-Patient:innen waren älter und weniger häufig HLA-B27 positiv, zudem war der Frauenanteil höher, als bei den axSpA+Pso-Patient:innen. Die Krankheitslast gemessen z. B. an der globalen Krankheitsaktivität berichtet sowohl von den Ärzten als auch von den Patient:innen war sehr ähnlich in beiden Gruppen. Damit die Daten aus Krankheitsregistern nutzbringend analysiert werden können und zum Beispiel auch Analysen über Therapiesicherheit möglich sind, ist es wichtig, dass möglichst viele Patient:innen eingeschlossen werden und über eine lange Zeit im Register beobachtet werden. Deshalb freuen wir uns sehr über die aktive Mitarbeit so vieler Rheumtaolog:innen und ihrer Mitarbeiter:innen und heißen neue rheumatologische Einrichtungen jederzeit herzlich willkommen.

Authors: Anne C. Regierer, Anja Weiß

Date Published: 2024

Publication Type: Journal

[RABBIT-SpA: a new disease register for axial spondyloarthritis and psoriatic arthritis]

Abstract (Expand)

BACKGROUND: The treatment of axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) has changed enormously in recent years due to market authorization of a number of new biologicals with different … modes of action and the increasing use of biosimilars. Real-world data on long-term safety and efficacy under routine daily conditions is not yet sufficient. Therefore, the German Rheumatism Research Center has initiated a new cohort study covering axSpA and PsA. OBJECTIVE: Presentation of initial results from the new register RABBIT-SpA, which was started in May 2017. MATERIAL AND METHODS: This is a prospective longitudinal cohort study with a similar study design to the German biologics register RABBIT. Patients can be included at the start of a new treatment either in the so-called index drug group or in the comparison group (conventional systemic treatment, including non-steroidal anti-inflammatory drugs, NSAID). Follow-up per patient should be at least 5 years and preferably 10 years. The RABBIT-SpA uses a web-based documentation system. RESULTS: Up to mid-December 2018 a total of 514 axSpA patients had been documented in RABBIT-SpA, 410 with an index drug and 104 with conventional treatment. There are differences between these treatment groups, e. g. in the duration of the disease and in parameters of disease activity. It is also noticeable that in axSpA patients, approximately 5 years lie between the onset of the symptoms and confirmation of the diagnosis. Of the 355 PsA patients, 265 were included with an index drug and 90 with conventional treatment. Of the PsA patients 86% have a dominant peripheral manifestation. The average number of pressure tender joints is 8 and the average number of swollen joints is 4. CONCLUSION: The online register RABBIT-SpA is well-received by the participating rheumatological institutions. The electronic recording of patient data can be carried out in a reasonable time. Participation in the RABBIT-SpA is open to new rheumatological institutions at any time.

Authors: A. C. Regierer, A. Weiss, X. Baraliakos, A. Zink, J. Listing, A. Strangfeld

Date Published: 2020

Publication Type: Journal

The Sensitivity to Change of the ASAS Health Index in an Observational Real-Life Cohort Study

Abstract (Expand)

Objective The Assessment of Spondyloarthritis international Society Health Index (ASAS HI) measures global functioning and health in patients with axial spondyloarthritis (axSpA) covering domains of … physical, emotional, and social functioning. The main aim of this study was to investigate the sensitivity to change of ASAS HI in comparison with established variables of disease activity, function, and mental health.Methods Patients with axSpA from the disease register RABBIT-SpA with follow-up time of at least 12 months and available ASAS HI questionnaires were included. Patients received questionnaires addressing disease activity (Bath Ankylosing Spondylitis Disease Activity Index [BASDAI], Ankylosing Spondylitis Disease Activity Score [ASDAS]), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]), mental health (5-item World Health Organization Well-Being Index [WHO-5]), and global functioning (ASAS HI). Standardized response means (SRMs) were calculated to compare the sensitivity to change of different variables.Results Six hundred and sixty-seven patients were included, 552 treated with biologic disease-modifying antirheumatic drugs (bDMARDs) and 115 with conventional synthetic DMARDs and/or nonsteroidal antiinflammatory drugs (control group). Between baseline and month 12, the mean ASAS HI declined from 6.9 to 5.1 in the bDMARD group and from 5.9 to 5.6 in the conventionally treated group. In the bDMARD group, the SRM of ASAS HI was 0.52, compared to 0.59 for BASFI, 0.65 for WHO-5, 0.73 for BASDAI, and 0.90 for ASDAS. The following ASAS HI domains were most frequently affected: pain (78% agreed), maintaining body position (75%), and energy/drive (73%). In the patients receiving bDMARDs, there was an improvement in all items. In the control group, the largest improvement was seen in pain.Conclusion As expected, ASDAS and BASDAI as disease activity scores showed high sensitivity to change, whereas changes in physical function (BASFI), mental health (WHO-5), and the broader concept of functioning and health (ASAS HI) were moderate.

Authors: Anne C. Regierer, Anja Weiß, Uta Kiltz, Joachim Sieper, Ilka Schwarze, Martin Bohl-Bühler, Herbert Kellner, Denis Poddubnyy, Angela Zink, Jürgen Braun, Joachim Listing, Anja Strangfeld

Date Published: 2023

Publication Type: Journal

Comparison of patients with axial PsA and patients with axSpA and concomitant psoriasis: an analysis of the German register RABBIT-SpA

Abstract (Expand)

BACKGROUND: Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) show certain overlaps: A subset of patients with PsA can develop axial involvement (axial PsA, axPsA), while a subset of patients … with axSpA presents with psoriasis (axSpA+pso). Treatment strategy for axPsA is mostly based on axSpA evidence. OBJECTIVES: To compare demographic and disease-specific parameters of axPsA and axSpA+pso. METHODS: RABBIT-SpA is a prospective longitudinal cohort study. AxPsA was defined based on (1) clinical judgement by rheumatologists; (2) imaging (sacroiliitis according to modified New York criteria in radiographs or signs of active inflammation in MRI or syndesmophytes/ankylosis in radiographs or signs of active inflammation in spine MRI). axSpA was stratified into axSpA+pso and axSpA without pso. RESULTS: Psoriasis was documented in 181/1428 axSpA patients (13%). Of 1395 PsA patients, 359 (26%) showed axial involvement. 297 patients (21%) fulfilled the clinical definition and 196 (14%) the imaging definition of axial manifestation of PsA. AxSpA+pso differed from axPsA regardless whether clinical or imaging definition was used. axPsA patients were older, more often female and less often HLA-B27+. Peripheral manifestations were more often present in axPsA than in axSpA+pso, whereas uveitis and inflammatory bowel disease were more common in axSpA+pso. Burden of disease (patient global, pain, physician global) was similar among axPsA and axSpA+pso patients. CONCLUSIONS: AxPsA differs from axSpA+pso in its clinical manifestations, irrespective of whether axPsA is defined clinically or by imaging. These findings support the hypothesis that axSpA and PsA with axial involvement are distinct entities, so extrapolation of treatment data from randomised controlled trials in axSpA should be performed with caution.

Authors: A. C. Regierer, A. Weiss, F. Proft, X. Baraliakos, F. Behrens, D. Poddubnyy, G. Schett, H. M. Lorenz, M. Worsch, A. Strangfeld

Date Published: 2023

Publication Type: Journal

Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort

Abstract (Expand)

BACKGROUND: In patients with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA), concomitant depression might have a negative impact on the course of disease and treatment outcomes. The aims … of this analysis are to determine the prevalence of depressive symptoms in axSpA and PsA patients in a real-world cohort study and to identify sociodemographic and clinical associated factors for moderate or severe depressive symptoms in both diseases. METHODS: Patients from the RABBIT-SpA cohort with an axSpA or PsA diagnosis and a valid WHO-5 Well-Being Index score at baseline were included. A descriptive analysis of baseline and outcome parameters by category of depressive symptoms was performed and factors associated with the presence of depressive symptoms (moderate or severe) were examined in a logistic regression. RESULTS: Two thousand four hundred seventy patients (1,245 axSpA; 1,225 PsA) were included in the analysis. In both diagnoses, the proportion of patients with moderate depressive symptoms was 8% and 21% with severe symptoms. Patients with moderate or severe depressive symptoms were less likely to engage in sports than those with no or mild depressive symptoms, had more comorbidities and higher scores for disease activity, functional limitations, fatigue, and pain and took more analgesics. In axSpA, patients with a higher disease activity, a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms, while patients with more years in education and engaging in sports for at least 1 h/week were less likely to experience depressive symptoms. PsA patients with a greater functional impairment and more severe fatigue were more likely to experience depressive symptoms while those engaging in sports for at least 1 h/week were less likely to experience depressive symptoms. CONCLUSION: We confirmed a high prevalence of depressive symptoms in both PsA and axSpA. Factors negatively associated with the presence of depressive symptoms were fatigue, not engaging in sports, and greater functional limitations. Depressive symptoms may affect the perception of disease activity / severity by patients. Thus, depressive symptoms are an important condition in axSpA and PsA that should be considered when evaluating disease activity and treatment outcomes.

Authors: A. Reich, A. Weiss, L. Lindner, X. Baraliakos, D. Poddubnyy, S. Zinke, C. Stille, A. Strangfeld, A. C. Regierer

Date Published: 2023

Publication Type: Journal

Correction: Depressive symptoms are associated with fatigue, poorer functional status and less engagement in sports in axSpA and PsA: an analysis from the RABBIT-SpA cohort

Abstract

Not specified

Authors: A. Reich, A. Weiss, L. Lindner, X. Baraliakos, D. Poddubnyy, S. Zinke, C. Stille, A. Strangfeld, A. C. Regierer

Date Published: 2024

Publication Type: Journal

Effect of depressive symptoms on treatment response in patients with axSpA: data from the RABBIT-SpA register

Abstract (Expand)

OBJECTIVES: This analysis aimed to evaluate the effect of depressive symptoms on treatment outcomes in patients with axial spondyloarthritis (axSpA), focusing on low disease activity (LDA) and inactive … disease (ID) at 3 and 6 months after the start of a new systemic therapy. METHODS: This analysis used data from the longitudinal, observational RABBIT-SpA register. Depressive symptoms were assessed using the WHO-5 Well-Being Index, with scores below 29 indicating moderate-to-severe symptoms. The treatment outcomes LDA and ID, based on the Axial Spondyloarthritis Disease Activity Score with C-reactive protein, were evaluated after 3 and 6 months. Logistic regression models adjusted for confounding variables, selected via a directed acyclic graph, were used to assess the relationship between baseline depressive symptoms and treatment outcomes. Multiple imputation was used to handle missing data. RESULTS: A total of 1755 patients with axSpA were included in the analysis. Moderate-to-severe depressive symptoms were present in 29% of patients at baseline. Fewer patients with moderate-to-severe depressive symptoms reached LDA or ID at 3 months and 6 months compared with those with no or mild symptoms. Logistic regression analysis showed that depressive symptoms were associated with lower odds of reaching LDA or ID at both time points. CONCLUSION: Depressive symptoms have a significant and independent negative effect on treatment response in patients with axSpA, particularly in achieving LDA and ID. These findings highlight the importance of routine mental health screening and treatment of depressive symptoms in axSpA management to optimise disease outcomes.

Authors: A. Reich, A. Weiss, L. Lindner, S. Zinke, C. Stille, J. Detert, D. Poddubnyy, A. Strangfeld, X. Baraliakos, A. C. Regierer

Date Published: 2025

Publication Type: Journal

Biosimilars in den deutschen Biologika-Registern RABBIT und RABBIT-SpA

Abstract

Not specified

Authors: A Strangfeld, A Regierer, A Zink

Date Published: 2021

Publication Type: Journal

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EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update.

Abstract (Expand)

OBJECTIVES: To update the existing European Alliance of Associations for Rheumatology (EULAR) points to consider (PtC) for use of antirheumatic drugs in reproduction, pregnancy, and lactation, including … additional drugs and adverse outcomes as well as paternal drug safety. METHODS: According to the EULAR standardised operating procedures, an international task force (TF) defined the questions for a systematic literature review, followed by formulation of the updated statements. A predefined voting process was applied to each overarching principle and statement. Level of evidence and strength of recommendation were assigned, and participants finally provided their level of agreement for each item. RESULTS: The TF proposes 5 overarching principles and 12 recommendations for the use of antirheumatic drugs before and during pregnancy, through lactation, and in male patients. The current evidence indicates that synthetic disease-modifying antirheumatic drugs (DMARDs) compatible with pregnancy include antimalarials, azathioprine, colchicine, cyclosporine, sulfasalazine, and tacrolimus. Regarding nonsteroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids, a more restrictive approach to their use during pregnancy is recommended. Based on an individualised risk-benefit assessment, all tumour necrosis factor inhibitor (TNFi) biologic DMARDs (bDMARDs) can be used throughout pregnancy, and non-TNFi bDMARDs may be used if needed. In relation to lactation, compatible drugs include antimalarials, azathioprine, colchicine, cyclosporine, glucocorticoids, intravenous immunoglobulin (IVIG), NSAIDs, sulfasalazine, and tacrolimus. All bDMARDs are considered compatible with breastfeeding. Concerning the use of drugs in men, compatible options include antimalarials, azathioprine, colchicine, cyclosporine, IVIG, leflunomide, methotrexate, mycophenolate, NSAIDs, glucocorticoids, sildenafil, sulfasalazine, tacrolimus, and bDMARDs. CONCLUSIONS: The updated recommendations provide consensus guidance and will help to improve the quality of care of patients during the phases of reproduction, pregnancy, and lactation.

Authors: L. Ruegg, A. Pluma, S. Hamroun, I. Cecchi, L. F. Perez-Garcia, P. O. Anderson, L. Andreoli, S. B. Wirstrom, V. Boyadhzieva, C. Chambers, N. Costedoat-Chalumeau, R. J. E. M. Dolhain, R. Fischer-Betz, I. Giles, C. Gotestam-Skorpen, M. Hoeltzenbein, F. Marchiori, K. Mayer-Pickel, A. Molto, C. Nelson-Piercy, O. H. Nielsen, A. Tincani, M. Wallenius, A. Zbinden, Y. Meissner, A. Finckh, F. Forger

Date Published: 8th Jun 2025

Publication Type: Journal

EULAR recommendations for a core data set for pregnancy registries in rheumatology.

Abstract (Expand)

BACKGROUND AND OBJECTIVE: There is an urgent need for robust data on the trajectories and outcomes of pregnancies in women with inflammatory rheumatic diseases (IRD). In particular when rare outcomes … or rare diseases are to be investigated, collaborative approaches are required. However, joint data analyses are often limited by the heterogeneity of the different data sources.To facilitate future research collaboration, a European League Against Rheumatism (EULAR) Task Force defined a core data set with a minimum of items to be collected by pregnancy registries in rheumatology covering the period of pregnancy and the 28-day neonatal phase in women with any underlying IRD. METHODS: A stepwise process included a two-round Delphi survey and a face-to-face meeting to achieve consensus about relevant items. RESULTS: A total of 64 multidisciplinary stakeholders from 14 different countries participated in the two rounds of the Delphi process. During the following face-to-face meeting of the EULAR Task Force, consensus was reached on 51 main items covering 'maternal information', 'pregnancy' and 'treatment'. Generic instruments for assessment are recommended for every item. Furthermore, for the five most frequent IRDs rheumatoid arthritis, spondyloarthritis, juvenile idiopathic arthritis, systemic lupus erythematosus and other connective tissue diseases, disease-specific laboratory markers and disease activity measurements are proposed. CONCLUSION: This is the first consensus-based core data set for prospective pregnancy registries in rheumatology. Its purpose is to stimulate and facilitate multinational collaborations that aim to increase the knowledge about pregnancy course and safety of treatment in women with IRDs during pregnancy.

Authors: Y. Meissner, R. Fischer-Betz, L. Andreoli, N. Costedoat-Chalumeau, D. De Cock, R. J. E. M. Dolhain, F. Forger, D. Goll, A. Molto, C. Nelson-Piercy, R. Ozdemir, L. Raio, S. C. Rodriguez-Garcia, S. Sciascia, M. Wallenius, A. Zbinden, A. Zink, A. Strangfeld

Date Published: 16th Oct 2020

Publication Type: Journal

Re-treatment with etanercept is as effective as the initial firstline treatment in patients with juvenile idiopathic arthritis

Abstract

Not specified

Authors: Jens Klotsche, Ariane Klein, Martina Niewerth, Paula Hoff, Daniel Windschall, Ivan Foeldvari, Johannes-Peter Haas, Gerd Horneff, Kirsten Minden

Date Published: 1st Apr 2021

Publication Type: Journal

Pregnancy outcomes in DMARD-exposed patients with juvenile idiopathic arthritis—results from a JIA biologic registry

Abstract

Not specified

Authors: Paula Drechsel, Katrin Stüdemann, Martina Niewerth, Gerd Horneff, Rebecca Fischer-Betz, Eva Seipelt, Susanna Spähtling-Mestekemper, Peer Aries, Angela Zink, Jens Klotsche, Kirsten Minden

Date Published: 1st Aug 2019

Publication Type: Journal

Time of Disease‐Modifying Antirheumatic Drug Start in Juvenile Idiopathic Arthritis and the Likelihood of a Drug‐Free Remission in Young Adulthood

Abstract

Not specified

Authors: Kirsten Minden, Gerd Horneff, Martina Niewerth, Eva Seipelt, Martin Aringer, Peer Aries, Ivan Foeldvari, Johannes‐Peter Haas, Ariane Klein, Stefanie Tatsis, Klaus Tenbrock, Angela Zink, Jens Klotsche

Date Published: 1st Mar 2019

Publication Type: Journal

Time spent in inactive disease before MTX withdrawal is relevant with regard to the flare risk in patients with JIA

Abstract

Not specified

Authors: Jens Klotsche, Kirsten Minden, Martina Niewerth, Gerd Horneff

Date Published: 1st Jul 2018

Publication Type: Journal

Outcome of adult patients with JIA treated with the biosimilar Benepali\textregistered: results of the biologic register JuMBO

Abstract

Not specified

Authors: Kristina Vollbach, Klaus Tenbrock, Nobert Wagner, Gerd Horneff, Ariane Klein, Ivan Foeldvari, Johannes-Peter Haas, Peer Aries, Georg Gauler, Frank Striesow, Paula Hoff, Christine Scholz, Stefanie Tatsis, Eva Seipelt, Jens Klotsche, Kirsten Minden

Date Published: 1st Dec 2022

Publication Type: Journal

Burden of comorbid conditions in children and young people with juvenile idiopathic arthritis: a collaborative analysis of 3 JIA registries

Abstract

Not specified

Authors: Lianne Kearsley-Fleet, Jens Klotsche, Joeri W van Straalen, Wendy Costello, Gianfranco D’Angelo, Gabriella Giancane, Gerd Horneff, Ariane Klein, Matilda Láday, Mark Lunt, Sytze de Roock, Nicolino Ruperto, Casper Schoemaker, Gordana Vijatov-Djuric, Jelena Vojinovic, Olga Vougiouka, Nico M Wulffraat, Kimme L Hyrich, Kirsten Minden, Joost F Swart

Date Published: 1st Oct 2021

Publication Type: Journal

Long-term outcome of patients with JIA treated with etanercept, results of the biologic register JuMBO

Abstract

Not specified

Authors: K. Minden, M. Niewerth, A. Zink, E. Seipelt, I. Foeldvari, H. Girschick, G. Ganser, G. Horneff

Date Published: 1st Mar 2012

Publication Type: Journal

Biologikatherapie der juvenilen idiopathische Arthritis im jungen Erwachsenenalter: Übergang von der pädiatrischen in die Erwachsenenversorgung

Abstract

Not specified

Authors: M. Niewerth, K. Minden, J. Klotsche, G. Horneff

Date Published: 1st Aug 2014

Publication Type: Journal

Biologikaregister JuMBO: Langzeitsicherheit von Biologikatherapie bei juveniler idiopathischer Arthritis

Abstract

Not specified

Authors: K. Minden, J. Klotsche, M. Niewerth, G. Horneff, A. Zink

Date Published: 1st Mar 2013

Publication Type: Journal

Medication burden in young adults with juvenile idiopathic arthritis: data from a multicentre observational study

Abstract

Not specified

Authors: Laura J Montag, Gerd Horneff, Paula Hoff, Ariane Klein, Tilmann Kallinich, Ivan Foeldvari, Eva Seipelt, Stefanie Tatsis, MD Peer Aries, Martina Niewerth, Jens Klotsche, Kirsten Minden

Date Published: 1st Oct 2022

Publication Type: Journal

Assessing Competencies, Needs, and Satisfaction With the Transition From Pediatric to Adult Health Care in Rheumatology: Development and Validation of the Transition-KompAZ

Abstract

Not specified

Authors: Henriette Haney, Jens Klotsche, Martina Niewerth, Sandra Hansmann, Gabi Erbis, Christiane Reiser, Sebastian Jonas Saur, Paula Hoff, Eva Seipelt, Anna Maier, Susanne Schalm, Stefanie Tatsis, Ivan Foeldvari, Ina Kötter, Kirsten Minden

Date Published: 1st Aug 2024

Publication Type: Journal

Mental comorbidities in adolescents and young adults with juvenile idiopathic arthritis: an analysis of German nationwide health insurance data

Abstract

Not specified

Authors: Florian Milatz, Katinka Albrecht, Kirsten Minden, Ursula Marschall, Jens Klotsche, Johanna Callhoff

Date Published: 2024

Publication Type: Journal

First-year follow-up of children with chronic nonbacterial osteomyelitis—an analysis of the German National Pediatric Rheumatologic Database from 2009 to 2018

Abstract

Not specified

Authors: Christiane Reiser, Jens Klotsche, Anton Hospach, Rainer Berendes, Anja Schnabel, Annette F. Jansson, Markus Hufnagel, Nadine Grösch, Martina Niewerth, Kirsten Minden, Hermann Girschick

Date Published: 1st Nov 2021

Publication Type: Journal

Long-term follow-up of children with chronic non-bacterial osteomyelitis—assessment of disease activity, risk factors, and outcome

Abstract

Not specified

Authors: Christiane Reiser, Jens Klotsche, Toni Hospach, Georg Heubner, Daniel Windschall, Ralf Trauzeddel, Nadine Groesch, Martina Niewerth, Kirsten Minden, Hermann Girschick

Date Published: 1st Nov 2023

Publication Type: Journal

Participation in school sports among children and adolescents with juvenile idiopathic arthritis in the German National Paediatric Rheumatologic Database, 2000–2015: results from a prospective observational cohort study

Abstract

Not specified

Authors: Florian Milatz, Jens Klotsche, Martina Niewerth, Nils Geisemeyer, Ralf Trauzeddel, Elisabeth Weißbarth-Riedel, Tilmann Kallinich, Joachim Peitz, Matthias Hartmann, Kirsten Minden

Date Published: 1st Feb 2019

Publication Type: Journal

Prevalence of overweight in children and adolescents with juvenile idiopathic arthritis

Abstract

Not specified

Authors: S Schenck, M Niewerth, C Sengler, R Trauzeddel, A Thon, K Minden, J Klotsche

Date Published: 1st Mar 2015

Publication Type: Journal

Enthesitis-related Arthritis: Prevalence and Complications of Associated Uveitis in Children and Adolescents From a Population-based Nationwide Study in Germany

Abstract

Not specified

Authors: Karoline Walscheid, Karen Glandorf, Kai Rothaus, Martina Niewerth, Jens Klotsche, Kirsten Minden, Arnd Heiligenhaus

Date Published: 1st Mar 2020

Publication Type: Journal

Similarities in clinical course and outcome between juvenile idiopathic arthritis (JIA)-associated and ANA-positive idiopathic anterior uveitis: data from a population-based nationwide study in Germany

Abstract

Not specified

Authors: Arnd Heiligenhaus, Jens Klotsche, Martina Niewerth, Gerd Horneff, Gerd Ganser, Johannes-Peter Haas, Kirsten Minden

Date Published: 1st Apr 2020

Publication Type: Journal

Anxiety and depression symptoms in adolescents and young adults with juvenile idiopathic arthritis: results of an outpatient screening

Abstract

Not specified

Authors: Florian Milatz, Jens Klotsche, Martina Niewerth, Claudia Sengler, Daniel Windschall, Tilmann Kallinich, Frank Dressler, Ralf Trauzeddel, Reinhard W. Holl, Ivan Foeldvari, Normi Brück, Svenja Temming, Toni Hospach, Petra Warschburger, Rainer Berendes, Gabriele Erbis, Jasmin B. Kuemmerle-Deschner, Frank Weller-Heinemann, Johannes-Peter Haas, Annabel S. Müller-Stierlin, Agnes Mutter, Thomas Meissner, Harald Baumeister, Kirsten Minden

Date Published: 1st Apr 2024

Publication Type: Journal

Level and correlates of physical activity among children and adolescents with juvenile idiopathic arthritis compared to controls: results from a German nationwide prospective observational cohort study

Abstract

Not specified

Authors: Florian Milatz, Sandra Hansmann, Jens Klotsche, Martina Niewerth, Tilmann Kallinich, Frank Dressler, Johannes-Peter Haas, Rainer Berendes, Gerd Horneff, Markus Hufnagel, Frank Weller-Heinemann, Daniel Windschall, Ralf Trauzeddel, Moritz Klaas, Hermann Girschick, Prasad T. Oommen, Ivan Foeldvari, Serdar Mustafa Cantez, Annette F. Jansson, Matthias Hartmann, Joachim Peitz-Kornbrust, Kirsten Minden

Date Published: 1st Mar 2024

Publication Type: Journal

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