Researchers report that one course of the IV drug rituximab (Rituxan®, Genentech and Biogen Idec) reduced disease activity and relapses for 48 weeks in people with relapsing-remitting (RR) MS*. Rituximab depletes immune B cells, which may play a role in the immune attack on brain and spinal cord tissues in MS. Dr. Stephen Hauser (University of California at San Francisco) and colleagues report these results in the February 14, 2008 issue of The New England Journal of Medicine. The clinical trial was supported by Biogen Idec and Genentech. Larger and longer-term studies are needed to confirm the drug’s safety and effectiveness.
The phase 2 trial was conducted at 32 centers in the U.S. and Canada. Two infusions of rituximab were administered two weeks apart to 69 people, and inactive placebo to 35 people. The primary goal of the study was to determine the drug’s effect on “enhancing” brain lesions (areas of tissue damage that glow with a contrast agent to signal active inflammation) at weeks 12, 16, 20 and 24. Other goals included the proportion of patients who experienced relapses. The number of active lesions at 24 weeks was reduced by 91% in the group taking rituximab versus those on placebo, and 58% fewer people in the treatment group had relapses (14.5% vs. 34.3%). More infusion-related reactions occurred in the group taking rituximab.
Of the 104 patients, 79 completed 48 weeks. The original results the reduction in number of active lesions and in the proportion of people having relapses compared with the placebo group were maintained at 48 weeks.
These findings not only herald the potential of a new therapeutic strategy for MS, but they also may shed light on the immunologic mechanisms leading to the disease, writes MS expert Henry F. McFarland, MD (NINDS, Bethesda, MD) in an accompanying editorial. Rituximab treatment showed benefit as early as four weeks. This suggests that the clinical benefit of depleting B cells may not be as it has been believed to be from curbing their production of immune system antibodies. For decades, immune T cells have been thought to be the main culprits in MS, and the rituximab study raises the possibility that interactions between B cells and T cells may be key to the destructive action of the immune system in MS.
Dr. McFarland cautions, however, that some antibodies produced by B cells have been found to induce tissue repair, so investigators conducting phase 3 trials should conduct long-term, careful monitoring of participants.
Rituximab is approved for use with certain types of lymphoma and a form of arthritis. The drug has been associated with severe adverse effects including fatal infusion reactions and progressive multifocal leukoencephalopathy, but these have not occurred in the MS studies. A large-scale clinical trial of rituximab is also ongoing in 435 people with primary-progressive MS*.
-- Research and Clinical Programs Department
*Relapsing-Remitting MS is a course of MS characterized by clearly defined flare-ups followed by partial or complete recovery periods (remissions) free of disease progression.
**Primary-progressive MS is a course of MS characterized by a slow but nearly continuous worsening of disease from the onset.
Rituxan is a registered trademark of Genentech and Biogen Idec