[Register and cohort studies : Overview of the most important data sources at the German Rheumatism Research Center]. / Register- und Kohortenstudien : Eine Übersicht über die wichtigsten Datenquellen am Deutschen Rheuma-Forschungszentrum.

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.

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

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.

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

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-α 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.

[How frequent are poor prognostic markers in rheumatoid arthritis? : An estimate based on three epidemiologic cohorts]. / Wie häufig sind prognostisch ungünstige Faktoren bei Patienten mit rheumatoider Arthritis? : Eine Abschätzung anhand von 3 epidemiologischen Kohorten.

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)-naïve 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/1st/2nd/3rd DMARD; n = 5707). RESULTS: In DMARD-naïve patients (CAPEA), 50% presented with DAS28 > 5.1, 64% were ACPA/RF+, 13% had erosions, and 37% functional disability (FFbH < 70). In RABBIT, 63 (1st 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-naïve) 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.