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213 Publications visible to you, out of a total of 213
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

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

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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

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

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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

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

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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

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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

[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

[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

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