Objectives To conduct an updated overall safety analysis of rituximab (RTX) in RA patients in the global clinical trial programme.
Methods Pooled observed case analysis of safety data from patients with moderate to severe active RA treated with RTX+MTX. 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). Pooled data from patients who received placebo during placebo-controlled study periods were also analysed.
Results As of Sep 2012, 3595 patients (All-Exposure population) had received up to 20 courses of RTX over the 11-yr observation period (14 816 pt-yrs). Of these patients, 1246 had >5yrs follow-up. The placebo population comprised 818 patients (1107 pt-yrs) with a mean follow-up of 1–1.5 yrs. In the All-Exposure population, infusion-related reaction (IRR) was the most frequent adverse event (AE); most were grade 1 or 2, were rarely serious (0.5%), and primarily occurred following the 1st infusion of the 1st course (799/3595 patients; 22%). Rates per 100 pt-yrs for AEs, serious AEs (SAEs), and infections were not increased when compared to placebo (Table). Overall the serious infection rate in RTX-treated patients was comparable to that observed in placebo patients. Pneumonia was the most frequently reported serious infection (2% of RTX patients). There were no cases of hepatitis B reactivation. Serious opportunistic infections were rare (0.05/100 pt-yrs in RTX patients vs 0.09/100 pt-yrs in placebo). One confirmed case of PML in the RA clinical trial programme has been reported, as previously described.1 Following RTX treatment low immunoglobulin (Ig) concentrations (particularly IgM, less often IgG) were observed. For both Ig classes, serious infection rates were similar before and during/after development of low Ig. No increased risk of malignancy over time or course was evident, and MI rates (0.39/100 pt-yrs) were consistent with rates in the general RA population (0.48–0.59/100 pt-yrs).2
Conclusions These long-term data from 3595 patients with up to 11-yr follow-up (14 816 pt-yrs) confirm that RTX remains well tolerated over time and multiple courses with a consistent safety profile. No new safety signals were observed with increasing duration of exposure. Apart from IRRs and low Ig (where there was a lack of placebo comparator), 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 and with previous analyses of this patient cohort.
Fleischmann RM. Arthritis Rheum 2009;60:3225;
British Society for Rheumatology Biologics Register, 2007
Disclosure of Interest R. van Vollenhoven Grant/research support from: Abbott, GSK, Merck, Pfizer, Roche, UCB, BMS, Consultant for: Abbott, GSK, Merck, Pfizer, Roche, UCB, BMS, P. Emery Consultant for: Pfizer, Merck, Abbott, BMS, Roche, Novartis, C. Bingham Grant/research support from: Roche, Genentech Inc., Biogen/IDEC, Consultant for: Roche, Genentech Inc., E. Keystone Grant/research support from: Abbott, Amgen, AstraZeneca, Bristol-Meyers Squibb, Janssen, Roche, Genzyme, Merck, Novartis, Pfizer, UCB, Consultant for: Abbott, AstraZeneca, Biotest, Bristol-Meyers Squibb, Roche, Genentech Inc., 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 Inc., UCB, Consultant for: Abbott, Actelion, Amgen, BMS, BiogenIdec, Centocor, CORRONA, Gilead, GSK, NIH, Novartis, Pfizer, Roche/Genentech Inc., UCB, Speakers bureau: Abbott, Actelion, UCB (CME ONLY), E. Hessey Shareholder of: F. Hoffmann La-Roche, Employee of: Roche Products Limited, A. Vashishtha Employee of: Genentech Inc., A. Mehbob Employee of: Roche Products Limited, P. Lehane Employee of: Roche Products Limited