Rituxan Shows Promise In Treating RA

In June 2006, a team of scientists funded by Genentech and Biogen Idec, Inc. announced positive results from a Phase III clinical study of Rituxan (Rituximab) in adult patients with moderately-to-severely rheumatoid arthritis. The results were first presented at a rheumatology meeting in Amsterdam, Netherlands. The team was lead by Edward Keystone, M.D. of the University of Toronto.

Rituxan, the first and only CD20-positive B-cell-targeted therapy for rheumatoid arthritis (RA), was recently approved by the U.S. Food and Drug Administration. While RA has traditionally been considered a T-cell-mediated disease, newer research suggests that other immune cells called B-cells may play multiple roles in the development of RA. These roles include the production of antibodies that trigger immune attacks against a person's own cells, thus perpetuating the disease, and production of cytokines, which have shown to promote inflammation and joint damage. Rituxan itself is a therapeutic antibody that targets and selectively depletes CD20-positive B-cells without targeting stem cells or existing plasma cells.

In this multi-center, double-blind, placebo-controlled REFLEX study, patients were randomized to receive either a single treatment course of two infusions of Rituxan (1000 mg twice monthly) or placebo, in combination with a stable dose of methotrexate (MTX) and followed through 24 weeks. Following week 24, patients with active RA that had either demonstrated a response to an initial treatment course of Rituxan or had initially received placebo, were eligible for a subsequent or initial course of Rituxan treatment, respectively, and were followed through 56 weeks. X-rays of the hands and feet were taken at the start of the study and at weeks 24 and 56, and assessed using the Genant-modified Sharp method. The Genant-modified Sharp method focuses on 14 specific sites for evidence of bone erosion and 13 sites for narrowing of the joint space--both key measures of ongoing structural damage to the joints. Of the 520 total patients in the study, the analysis evaluated X-rays from 277 of the 311 Rituxan-treated patients and 186 of the 209 placebo-treated patients.

The most common adverse events observed in patients treated with Rituxan for RA in clinical trials were infusion reactions and infections. No significant change in average immunoglobulin levels was observed in Rituxan-treated patients in clinical trials. There was no increase in risk of opportunistic infections (including tuberculosis) in Rituxan-treated patients over the 24 weeks of treatment. Although 5 percent of Rituxan-treated RA patients developed human anti-chimeric antibodies (HACA), this was not associated with loss of clinical response or additional safety observations.

Article References
Analysis of Phase III Study Showed Rituxan Plus Methotrexate Reduced Joint Damage in Rheumatoid Arthritis Patients Who Respond Inadequately to TNF Antagonist Therapies, site accessed on 6/25/2006