OP0004 RITUXIMAB IN RA: EFFICACY AND SAFETY FROM A RANDOMISED, CONTROLLED TRIAL
H Stahl, L Szczepaski, J Szechiski, A Filipowicz-Sosnowska, J Edwards, D Close, R Stevens, T Shaw

Rituximab is an anti-CD20 monoclonal antibody that depletes B cells. The current study is a randomized, double-blind, placebo controlled trial in RA. The data presented here is a follow-up to the interim analysis of the first 120 patients reported during the 2002 ACR annual meeting (see interim results).

Methods: 161 RA patients were enrolled who were: 1) RF positive; 2) receiving MTX > 10 mg/wk; 3) had active disease (> 8 swollen and tender joints; elevated ESR/CRP). Forty patients each were randomized to 1 of 4 treatment groups: 1) MTX only; 2) Rituximab alone (2 x 1g IV on days 1 and 15); 3) Rituximab (2 x 1g IV) plus CTX (2 x 750 mg IV on days 3 amd 17); and 4) Rituximab (2 x 1g IV) and continued MTX. All groups also received a 17 day course of steroids (100 mg Solumedrol IV on days 1, 3, 15 and 17; 60 mg po on days 2 and 4-17), then tapering; 910 mg total).

Results: The primary outcome was ACR50 response at 6 months. Data in the table below represents the analysis of the 161 patients at week 24.

Adverse events were similar among all treatment groups, were mild or moderate in intensity, resolved without complication and predominantly included hypotension, pruritus, rash, and fever. 13 serious adverse events were reported, distributed among all treatment groups including MTX, and included 5 infections (one fatal).

Conclusion: Rituximab alone or in combination with CTX or MTX conferred additional benefit above MTX alone. The combination of rituximab with MTX was shown to be as efficacious as that with CTX. B cell depletion was well tolerated.

Editorial Comment: This study extends the results reported at the 2002 ACR meetings by the addition of 40 more patients into the protocol. The data confirm the efficacy of rituximab and the role of CD20+ B cells in rheumatoid arthritis. The study design is similar to other prior studies with TNF inhibitors. Rituximab is added to MTX in patients with active disease despite >10 mg of MTX weekly. These patients are not true MTX failures, but the MTX only arm of the study acts as a placebo group. The efficacy seen in the rituximab/MTX group is similar to that seen in the studies with TNF inhibitors used in combination with MTX. Arguably the patients studied are more severe with all patients failing multiple DMARDs and all are RF+. It is remarkable that patients have sustained efficacy at 6 months, 22 weeks after last receiving treatment with either rituximab or corticosteroids. The finding that cyclophosphamide can be replaced with MTX will be helpful to allay concerns about toxicity of the regimen. Many questions remain including durability of the response, long term toxicity and the effects of repeated dosing.

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