B cells in rheumatoid arthritis: from hypothesis to the clinic.
Rituximab (MabThera/Rituxan) is a therapeutic monoclonal antibody against CD20, an antigen expressed by B cells but not B-cell progenitor or plasma cells. It is currently approved for the treatment of relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) and is well tolerated and efficacious. A small open-label study (conducted by Edwards and Cambridge) indicated that selective depletion of B cells using rituximab led to sustained benefits for patients with active rheumatoid arthritis. A 24-week, double-blind, randomized controlled trial was carried out to confirm these initial observations. In total, 161 patients with active rheumatoid arthritis were randomized to one of four treatment groups: rituximab monotherapy; rituximab plus methotrexate (R+MTX); rituximab plus cyclophosphamide (R+CTX); or methotrexate alone (MTX). Rituximab was administered as two 1000 mg infusions on days 1 and 15. An analysis at 24 weeks showed that the proportion of patients achieving an ACR20 response was significantly greater (P < or = 0.025 for all three comparisons) in all the rituximab groups compared with the MTX control group (rituximab alone, 65%; R+CTX, 76%; R+MTX, 73%; MTX alone, 38%). Both ACR50 (43 vs 13%; P = 0.005) and ACR70 (23 vs 5%; P = 0.048) responses were also significantly higher for the R+MTX group compared with the MTX group. The rituximab groups showed no significant safety differences compared with the MTX arm. The majority of adverse events were of mild to moderate intensity. Rituximab is a novel targeted therapy for the treatment of rheumatoid arthritis and it appears to be highly effective, safe and well tolerated.
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The Rebecca MacDonald Centre for Arthritis and Autoimmune Disease, Mount Sinai Hospital, The Joseph and Wolf Lebovic Building, 2nd Floor, Room 2-006, 60 Murray Street, Toronto, Ontario M5G 1X5, Canada. ksnow@mtsinai.on.ca
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000276:immunology; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D018501:Antirheumatic Agents; D000069283:Rituximab