Guest guest Posted February 5, 2004 Report Share Posted February 5, 2004 Upcoming Biologic Agents for the Treatment of Rheumatic Diseases from Current Opinion in Rheumatology B-Cell-Directed Therapies Rituximab Rituximab (anti-CD20 antibody) is a monoclonal antibody that selectively depletes B cells bearing the CD20 surface marker. Depletion of immature, mature naïve, and memory B cells occurs through antibody-mediated and complement-mediated cytotoxicity. Plasma cells do not express CD20; therefore, immunoglobulin levels are not significantly affected by anti-CD20 treatment. This agent has been used widely in the treatment of B-cell lymphomas and is currently under study for use in human autoimmune diseases, especially those diseases characterized by autoantibody production.[78, 79*] Case reports suggest a possible role for rituximab in refractory WG,[80] SLE-associated hemolytic anemia,[81] idiopathic thrombocytopenic purpura,[82] and essential mixed cryoglobulinemia.[83] A phase I, dose-finding trial of rituximab in SLE is currently underway. Rituximab has also been shown to be surprisingly effective for the treatment of RA. An open-label trial of rituximab, administered as four weekly infusions, for active, refractory RA in five subjects resulted in ACR70 and ACR50 responses in one patient each and ACR20 responses in two other patients, while only one patient failed to respond. The clinical improvement occurred within 1 to 2 months of treatment and was maintained for 2 to 10 months after infusion.[84] Another research group treated 22 patients with various doses of rituximab in combination with cyclophosphamide and/or high-dose prednisolone.[85] The subjects tolerated the regimen well, and major responses were seen in subjects receiving higher doses of rituximab. Subjects who did not receive cyclophosphamide performed poorly compared with the cyclophosphamide-treated groups. In a phase II, placebo-controlled, randomized trial of rituximab in RA, subjects with active RA despite methotrexate were randomized to one of four treatment groups: methotrexate and placebo, rituximab alone, rituximab and cyclophosphamide, and rituximab and methotrexate. The rituximab dose was the same in all groups: two 1-g infusions. All subjects received a course of corticosteroids (a total of 960 mg over 17 days). Interim results found that ACR20 criteria were met by 58% treated with rituximab alone, 80% receiving rituximab and continuing methotrexate, and 84% treated with rituximab and cyclophosphamide, but only 33% of those treated with methotrexate and placebo. The primary outcome, ACR20 response, was measured at 24 weeks.[86**] http://www.medscape.com/viewarticle/452882_11 Quote Link to comment Share on other sites More sharing options...
Recommended Posts
Join the conversation
You are posting as a guest. If you have an account, sign in now to post with your account.
Note: Your post will require moderator approval before it will be visible.