Background Tocilizumab (TCZ) is an interleukin-6-receptor inhibitor for treatment of patients (pts) with rheumatoid arthritis (RA), which was approved in the EU in JAN 2009.
Objectives To evaluate the effectiveness, safety, and utilization of TCZ in a usual care setting in Germany.
Methods ROUTINE is a prospective, non-interventional study with 174 study sites (specialized rheumatologists or hospital units) across Germany. Included pts were to be treated according to the Summary of Product Characteristics (SmPC); the individual observation period was 52 weeks.
Main study objectives were to assess the physicians’ adherence to SmPC when treating their pts, occurrence of infections and other adverse events (AEs), and post-baseline changes in disease activity up to Week 52. All statistical analyses were purely descriptive. Additional subgroup analyses considered prior RA treatment (conventional DMARDs [cDMARDs] vs. TNF inhibitors [TNFi]) and the use of other concomitant RA drugs in addition to TCZ (TCZ combination therapy vs. monotherapy).
Results A total of 850 pts (mean age: 56±13 years; 75% women) were analyzed. Mean disease duration was 10.3±8.6 years. Most pts (79%) had previously received TNFi, while 21% were previously treated only with cDMARDs. The most common previous RA treatments (>50% of pts) were the cDMARDs MTX (79%) and leflunomide (LEF, 68%), and the TNFi adalimumab (53%) and etanercept (50%). Mean number of previous DMARDs (both cDMARDs and TNFi) was 4.0±2.1.
Mean treatment duration on study was 329±133 days (median: 377 days). TCZ was generally dosed as recommended (ie, 8.0 mg/kg body weight). At baseline 60.5% of pts received TCZ in combination with other RA drugs (incl. steroids), while 39.5% were treated with TCZ as monotherapy. During the entire course of the study TCZ was mostly combined with MTX (77%), followed by LEF (20%), prednisolone (7%), sulfasalazine (6%), hydroxychloroquine (3%), and prednisone (2%; percentages based on 555 pts with combination treatment at any time). Mean steroids (prednisolone equivalent) decreased from 8.9±9.6 mg/day at baseline to 6.1±6.5 mg/day at Week 52.
Mean baseline DAS28 was 5.5±1.3 and decreased to 2.6±1.6 at Week 52 (observed data). At Week 52, “good” EULAR response was achieved in 62.3%, LDAS in 44.4%, and DAS remission in 55.1% of pts (percentages based on pts. with observation).
300 pts (35.3%) discontinued the study prematurely; most common reasons (>5%) were lack of effectiveness (10.5%), intolerability (7.3%), missing data (6.1%), and pt’s request (5.6%). Any acute infections and severe acute infections during the study period occurred in 314 and 60 pts (37.6% and 7.2%, respectively; N=836). Most of the infections were related to upper respiratory infections and usually completely resolved; 2 cases of tuberculosis were reported. Generally, incidence and pattern of AEs did not show new or unexpected findings.
Conclusions TCZ administered in usual care demonstrated clinically meaningful effectiveness, which was consistent with the efficacy results observed in the preceding pivotal studies. Likewise, the safety profile of TCZ in routine use was consistent with previous findings with TCZ.
Disclosure of Interest: G.-R. Burmester Consultant for: Abbott, BMS, MedImmune, MSD, Pfizer, Roche, UCB, Speakers bureau: Abbott, BMS, MSD, Pfizer, Roche, UCB, U. von Hinüber: None Declared, C. Richter: None Declared, H. Schwenke: None Declared, I. Gürtler: None Declared, P. Kästner: None Declared, M. A. Peters Employee of: Roche Pharma AG, C. Iking-Konert Consultant for: Roche Pharma AG; Chugai Pharma Marketing Ltd., Speakers bureau: Roche Pharma AG; Chugai Pharma Marketing Ltd.