| Abstract
| - Objectives. To evaluate the long-term safety of rituximab (RTX) in rheumatoid arthritis (RA) patients in a global clinical trial programme. Methods. A pooled observed case analysis of safety data from patients with moderate to severe active RA treated with RTX + methotrexate is presented. Patients were retreated based on physician’s determination of clinical need and evidence of active disease (defined as either SJC and TJC ≥8 or DAS28 ≥2.6). Subgroup analysis of patients with follow-up >5 years was undertaken. Pooled data from patients who received placebo during placebo-controlled study periods were also analysed. Results. As of September 2011, 3595 patients (All Exposure population) had received up to 19 courses of RTX over the 10-year observation period (14008 pt-yrs). Of these patients, 1145 had follow-up >5 years (7716 pt-yrs) (>5 year population). The placebo population comprised 818 patients (1107 pt-yrs) with a mean duration of follow-up of 1-1.5 years. In All Exposure population, infusion-related reaction (IRR) was the most frequent adverse event (AE); most of these were CTC grade 1 or 2, were rarely serious, and generally occurred following the first infusion of the first course (789/3595 patients; 22%). Rates of AEs, serious AEs (SAEs) and infections were comparable across analysis populations and generally remained stable over time and multiple courses (Table). Overall serious infection rates in the rituximab All Exposure and >5 year sub-population were 3.80 events/100 pt-yrs and 2.76 events/100 pt-yrs, respectively, both rates being comparable to that observed in the placebo population (3.79 events/100 pt-yrs). Pneumonia was the most frequently reported serious infection (2% of RTX patients). Serious opportunistic infections were rare (0.05/100 pt-yrs in RTX patients compared with 0.09/100 pt-yrs in placebo). No increased risk of malignancy over time or course was evident, and myocardial infarction rates (0.40 events/100 pt-yrs) were consistent with rates in the general RA population (0.48-0.59 events/100 pt-yrs).1 Table 1. AE rates per 100 pt-yrs (95% CI)RTX All ExposureRTX Long term (>5 yrs)Pooled placebo(n=3595) 14008 pt-yrs(n=1145) 7716 pt-yrs(n=818) 1107 pt-yrsAEs249.34 (246.74-251.97)237.25 (233.83-240.71)315.43 (305.14-326.06)SAEs14.03 (13.42-14.66)12.25 (11.49-13.05)13.82 (11.79-16.19)Infections78.60 (77.14-80.08)75.10 (73.19-77.06)90.39 (84.96-96.17)Serious infections3.80 (3.50-4.14)2.76 (2.41-3.16)3.79 (2.80-5.13) Conclusions. This analysis of safety data from 3595 patients with up to 10-year follow-up (14008 pt-yrs), demonstrates that RTX has a consistent safety profile and remains well tolerated over time and multiple treatment courses. No new safety signals were observed with increasing duration of exposure, including within a subgroup of patients with >5 years of follow-up. Apart from IRR, the overall safety profile of RTX remains similar to that of the pooled placebo population and is consistent with published data for moderate to severe RA. References. British Society for Rheumatology Biologics Register, 2007 Disclosure of Interest. R. van Vollenhoven Grant/Research support from: Abbott, GSK, Merck, Pfizer, Roche, UCB, Consultant for: Abbott, GSK, Merck, Pfizer, Roche, UCB, P. Emery Consultant for: Pfizer, Merck, Abbott, BMS, Roche, Novartis, C. Bingham Grant/Research support from: Roche, Genentech, Biogen/IDEC, Consultant for: Roche, Genentech, E. Keystone Grant/Research support from: Abbott, Amgen, AstraZeneca, Bristol-Meyers Squibb, Centocor, Roche, Genzyme, Merck, Novartis, Pfizer, UCB, Consultant for: Abbott, AstraZeneca, Biotest, Bristol-Meyers Squibb, Centocor, Roche, Genentech, Merck, Nycomed, Pfizer, UCB, R. Fleischmann Grant/Research support from: Genentech Inc, Roche, Consultant for: Genentech Inc, Roche, D. Furst Grant/Research support from: Abbott, Actelion, Amgen, BMS, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Consultant for: Abbott, Actelion, Amgen, BMS, BiogenIdec, Centocor, CORRONA, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech, UCB, Speakers Bureau: Abbott, Actelion, UCB (CME ONLY), N. Tyson Shareholder of: Roche Products Ltd, Employee of: Roche Products Ltd, A. Mehbob Employee of: Roche Products Ltd, P. Lehane Employee of: Roche Products Ltd
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