OP0046 LONG-TERM SAFETY OF RITUXIMAB: FOLLOW-UP OF THE RA CLINICAL TRIALS AND RETREATMENT POPULATION

R. F. van Vollenhoven ^1,*P. Emery ²C. O. Bingham ³E. Keystone ⁴R. Fleischmann ⁵D. E. Furst ⁶K. Macey ⁷M. Sweetster ⁸P. B. Lehane ⁷P. Farmer ⁹S. G. Long ⁷

¹Karolinska Institute, Stockholm, Sweden, ²Leeds General Infirmary, Leeds, United Kingdom, ³Johns Hopkins University, Baltimore, United States, ⁴University of Toronto, Toronto, Canada, ⁵University of Texas Southwestern Medical Center, Dallas, ⁶UCLA, Los Angeles, United States, ⁷Roche Products Ltd, Welwyn Garden City, United Kingdom, ⁸Biogen Idec, Cambridge, ⁹Genentech Inc, South San Francisco, United States

Objectives: To evaluate the long-term safety of rituximab (RTX) in RA patients (pts) in clinical trials.

Methods: Pooled analysis of safety data from pts treated with RTX plus methotrexate (MTX) in a global clinical trial programme. All pts were offered RTX retreatment based on physician decision of clinical need. Pts receiving placebo during placebo-controlled study periods were pooled to provide a placebo population.

Results: As of September 2009, 3189 pts had been treated with RTX providing 9342 pt-yrs of exposure. The analysis includes >9 yrs of follow-up with up to 15 courses of RTX. More than 1500 pts were followed for >3 yrs and 2417, 1724, 1392, 1036 and 656 pts received ≥2, ≥3, ≥4, ≥5 and ≥6 courses, respectively. Other than infusion-related reactions (IRR), the safety profile of RTX was similar to the placebo population or general RA populations. In the RTX group, the most frequent adverse event (AE) was IRR (35.6%); most were CTC grade 1 or 2 and occurred after the first infusion of the first course (23.0%), with 0.5% considered serious (over all courses). Rates of serious AEs (SAEs) and infections generally remained stable over time and over multiple RTX courses (Table). The overall serious infection rate was 4.35 events/100 pt-yrs, comparable to that observed in the placebo population (4.29 events/100 pt-yrs). The numerically higher serious infection rate at Course 5 was not seen at Course 6. The most frequent serious infections were of the lower respiratory tract, predominantly pneumonia (2%). Serious opportunistic infections were rare, but included one confirmed case of Pneumocystis jiroveci pneumonia in each of the RTX and placebo groups, and one previously reported case of progressive multifocal leukoencephalopathy (PML)¹ in the RTX group. Rates of myocardial infarction (0.49 events/100 pt-yrs) and stroke (0.25 events/100 pt-yrs) were consistent with rates in the general RA population (0.34–0.59 per 100 pt-yrs and 0.112–0.76 per 100 pt-yrs, respectively).^2–5

 Table: AE rates per 100 pt-yrs by course (C)

Conclusion: In prolonged follow-up of RA pts treated with RTX in clinical trials, RTX has remained well tolerated over time and over multiple courses, with a safety profile similar to that of the placebo population and consistent with published data on pts with moderate to severe RA.

References: ¹ Fleischmann, A&R, 2009 ²Pharmetrics Claims Database, 2006. ³ British Society for Rheumatology Biologics Register, 2007. ⁴ Nurses’ Health Study, 2003. ⁵ General Practice Research Database, 2003

Disclosure of Interest: R. van Vollenhoven Grant / Research Support from: Merck/Schering-Plough, Pfizer/Wyeth, Roche, Centocor, Inc, BMS, Abbott, Consultant for: BMS, Abbott, Centocor, Inc, Roche, Pfizer/Wyeth, Merck/Schering-PloughP. Emery Grant / Research Support from: Roche, Abbott Consultant for: Roche, Pfizer, Merck, Abbott, BMSC. Bingham Grant / Research Support from: Genentech, BMS, UCB, Abbott, Amgen Consultant for: Genentech, Roche, Merck, UCB, Centocor, SeronoE. Keystone Grant / Research Support from: Amgen Canada, Schering Plough Consultant for: Abbott, Roche, Amgen, BMS, Schering Plough, Wyeth, Centacor Inc, Genentech, UCBR. Fleischmann Shareholder of: Abbott, Astra Zeneca, GlaxoSmith Kline, Johnson and Johnson Grant / Research Support from: Amgen, Abbott, Centocor, UCB, Genentech, Roche, Biogen Idec, Pfizer, Bristol Myers Squibb, Regeneron, Lexicon, Medimmune Consultant for: Amgen, Abbott, Centocor, UCB, Pfizer, BMS Speakers Bureau: AmgenD. Furst Grant / Research Support from: Actelion, BMS, Celgene, Genentech, Gilead, NIH, Novartis, Roche, UCB Consultant for: Abbott, Actelion, Amgen, Array, BiogenIdec, BMS, Centocor, Genentech, Gilead, GSK, Encysive, Nitec, Novartis, Roche, TAP, UCB, Wyeth, XomaK. Macey Employee of: RocheM. Sweetster Shareholder of: Biogen-Idec Employee of: Biogen-IdecP. Lehane Employee of: RocheP. Farmer Employee of: GenetechS. Long Shareholder of: Roche Employee of: Roche