Objectives This phase III study evaluated the efficacy and safety of rituximab plus methotrexate (MTX) in patients with active rheumatoid arthritis (RA) who had an inadequate response to MTX and who were naïve to prior biological treatment.
Methods Patients with active disease on stable MTX (10–25 mg/week) were randomised to rituximab 2×500 mg (n=168), rituximab 2×1000 mg (n=172), or placebo (n=172). From week 24, patients not in remission (Disease Activity Score (28 joints) ≥2.6) received a second course of rituximab; patients initially assigned to placebo switched to rituximab 2×500 mg. The primary end point was American College of Rheumatology 20 (ACR20) response at week 24. All patients were followed until week 48.
Results At week 24, both doses of rituximab showed statistically superior efficacy (p<0.0001) to placebo (ACR20: 54%, 51% and 23%; rituximab (2×500 mg) + MTX, rituximab (2×1000 mg) + MTX and placebo + MTX, respectively). Secondary end points were also significantly improved for both rituximab groups compared with placebo. Further improvements in both rituximab arms were observed from week 24 to week 48. Rituximab + MTX was well tolerated, demonstrating comparable safety to placebo + MTX through to week 24, and between rituximab doses through to week 48.
Conclusions Rituximab (at 2×500 mg and 2×1000 mg) plus MTX significantly improved clinical outcomes at week 24, which were further improved by week 48. No significant differences in either clinical or safety outcomes were apparent between the rituximab doses.
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Funding This study was sponsored by Hoffmann-La Roche, Genentech and Biogen Idec.
Competing interests PE has received research grants and consulting fees from Roche and research grants from Abbott. AD has received payments for educational lectures, teleconferences and serving on advisory boards for Genentech, a company that may have a commercial interest in the results of this research. This potential conflict of interest has been reviewed and managed by OHSU. WFR has received speaker fees from Genentech, Abbott, Biogen Idec and Bristol-Myers Squibb; clinical trial payments from Genentech, Abbott, Roche and Bristol-Myers Squibb; and consulting fees from Genentech, Roche, Biogen Idec and Amgen. JDI has received consulting fees from Roche and speaker fees from Roche and Biogen Idec. BC has received speaker fees and consulting fees from Abbott, Bristol-Myers Squibb, Roche, Schering-Plough, UCB and Wyeth. KL has received speaker fees from Genentech, Abbott, Centocor and Bristol-Myers Squibb; clinical trial payments from Genentech, Centocor, Bristol-Myers Squibb and Amgen; and consulting fees from Genentech. AC is an employee of Genentech, a member of the Roche Group; GKA, WD and HT are employees of Roche. AJR, CA-M, LJS and RAR have no competing interests to declare.
Ethics approval Approval from the Independent Ethics Committee (IEC) was obtained before starting the study.
Provenance and peer review Not commissioned; not externally peer reviewed.