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216 Publications visible to you, out of a total of 216

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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

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

Abstract

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Author: A. Strangfeld

Date Published: 2017

Publication Type: Journal

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

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

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

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

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