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Rituximab in the Treatment of Rheumatoid Arthritis

A number of high-profile media reports heralded a study reported at the recent ACR annual meeting in Philadelphia as describing a possible cure for rheumatoid arthritis. Many patients and physicians have understandably expressed interest in the therapy.

News reports were a response to an abstract presented by Edwards et al.1 regarding the use of rituximab (Rituxan® in U.S., Mabthera® in Europe) in the treatment of rheumatoid arthritis. Rituximab is an anti-CD 20 chimeric mouse/human monoclonal antibody approved in 1997 for the treatment of B-cell lymphomas and has since been used in more than 50,000 patients. The monoclonal antibody has been shown to selectively deplete mature and malignant CD-20 positive pre B-and mature B-cells, and is the first monoclonal agent approved for cancer therapy. Based on their hypothesis that rheumatoid arthritis may be driven by auto-reactive B-lymphocytes, the authors utilized rituximab to deplete B-cells in five patients with refractory rheumatoid arthritis.

Five patients with refractory seropositive rheumatoid arthritis who had failed five or more disease modifying drugs, were treated with a four week course of rituximab in conjunction with prednisolone (60 mg. daily for 10 days, then 30 mg. daily for 12 days) and cyclophosphamide (750 mg. iv x2). At six months all patients achieved an ACR 50, and three achieved an ACR 70. Three had still achieved an ACR 70 at one year. The two who relapsed (at 7 and 9 months) were retreated and achieved an ACR 70. At 18 months all patients were classified as having a durable ACR 70 response. The effective lowering of rheumatoid factor titers and the number of circulating B-lymphocytes appear to correlate well with efficacy. These patients were able to discontinue all other DMARD use and no DMARDs were reintroduced. Despite prolonged B-lymphocyte depletion, no serious infections were encountered. Two patients developed lower respiratory tract infections requiring antibiotics, one patient developed petecchiae and thrombocytopenia in the second week of therapy and one patient had a local tissue reaction to cyclophosphamide. The investigators also claimed improvement in some extraarticular features (e.g., amyloidosis, nodules, anemia).

This novel study has resurrected the notion that RA may be a B cell driven process in some patients and that therapies aimed at curtailing the humoral response may be efficacious. Nonetheless, this is a very preliminary and uncontrolled trial in a small number of patients. Moreover, it is not certain to what extent cyclophosphamide and corticosteroids contributed to the therapeutic responses observed. More clinical research with this combination regimen is necessary before it can be applied in the clinic.

November 20, 2000
Robert Spiera, MD; John J. Cush, MD
Hotline Editors

1. Edwards JC, Cambridge G, Leandro MJ. Sustained improvement in rheumatoid arthritis following B lymphocyte depletion. Arthritis Rheum 43(9, SUPPL): S391, 2000.

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