R.F. van Vollenhoven1, S. Cohen 2 , K. Pavelka 3 , A. Kavanaugh 4 , P.P. Tak 5 , M. Greenwald 6 , M. Cravets 7 , P. Ward 8 , S. Agarwal 9 , F. Magrini 8. 1Rheumatology Dept, Karolinska University Hospital, Stockholm, Sweden, 2Radiant Research, Harry Hines Blvd, Dallas, TX, United States, 3Rheumatology Department, Institute of Rheumatology, Prague, Czech Republic, 4Rheumatology Div, UCSD, La Jolla CA, United States, 5Div. of Clinical Immunology and Rheumatology, University of Amsterdam, Amsterdam, Netherlands, 6Desert Medical Advances, Palm Desert, 7Biogen Idec, San Diego, CA, United States, 8Medical Sciences, Roche Products Ltd, Welwyn Garden City, United Kingdom, 9Clinical Development, Genentech Inc, South San Francisco, United States

Objectives: To evaluate response to repeated treatment courses and optimal frequency of repeated treatment with rituximab (RTX) in patients (pts) with active rheumatoid arthritis (RA).
Methods: Pts from the RTX clinical trial programme were eligible to enter an open-label repeated treatment study provided they met defined criteria (>/=20% improvement in joint counts) following a single course of RTX (C1) given within one of several Phase II/III studies in pts with an inadequate response to DMARDs including TNF inhibitors; this also included pts initially randomised to placebo. Each treatment course consisted of two infusions of RTX (1 g given 2 weeks apart as described previously). Active disease and a minimum 16-week interval between treatment courses were the only criteria for administering additional courses of RTX. Following repeated treatment courses, data were pooled for each pts first course of RTX (C1) and subsequent courses (C2-C3).
Results: 1039 pts were exposed to RTX; total exposure to treatment during the study was 1667 pt-years (839 pts had exposure >1 year; 139 >2 years; 89 >3 years). ACR response rates during C2 were comparable or improved relative to rates during C1; for pts who had prior exposure to TNF inhibitors, ACR 20, 50 and 70 scores were 65%, 33% and 12%, respectively, for C1, and 72%, 42% and 21%, respectively, for C2, relative to original baseline (n=155). There was no evidence of decreasing responses for C3, although the pt number was small. For both pt populations, the median interval between C1 and C2 was similar to C2 and C3 with no evidence of a decreased interval with further courses of treatment (Table). However, time to repeated treatment was artificially extended for those pts with no prior TNF inhibitor exposure as many of these were early study pts waiting for approval of the repeat treatment protocol. Repeated courses of treatment with RTX were generally well tolerated, with no new safety signals observed in the extension period.

Median time to repeat treatment (weeks)
Prior TNF (n=82)No prior TNF (n=50)
Second course (C2)30.936.7
Third course (C3)30.143.0

Conclusion: RTX, given as a single course of two infusions of RTX 2 weeks apart, is highly effective. The most appropriate interval between RTX treatment courses appears to lie between 6 and 12 months. RTX repeat treatment produces ACR responses that are comparable or improved relative to the first course of treatment; duration of effect is also comparable. RTX offers a fundamentally different approach to the treatment of RA, providing long-term duration of response after each treatment course.

Session: Rheumatic arthritis – treatment biologics
Citation: Ann Rheum Dis 2006;65(Suppl II):510


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