Cancer, Arthritis Drug May Help People With Multiple Sclerosis
By Salynn Boyles
WebMD Medical News Reviewed by Louise Chang, MD
Feb. 13 -- The novel cancer and rheumatoid arthritis drug Rituxan may prove to be a highly effective treatment for the most common form of multiple sclerosis, if results from a small, phase II trial are confirmed.
In the study, sponsored by the drug's manufacturers, patients with relapsing-remitting MS who were treated with a single course of Rituxan showed rapid reductions in the inflammatory brain lesions that are a hallmark of the disease.
And after nearly a year of follow-up, half as many patients treated with the drug had experienced clinically significant relapses as patients in the placebo arm of the study.
If the findings are confirmed in larger, phase III studies, the Rituxan research opens a new frontier for the study of the cause and treatment of MS, says lead author Stephen L. Hauser, MD, of the University of California, San Francisco (UCSF).
The study is published in the Feb. 14 issue of The New England Journal of Medicine.
"No matter what happens with Rituxan down the road, this represents a paradigm shift that has profound implications for our understanding of MS," he tells WebMD.
T Cells and B Cells
The leading treatments for MS target the T cells. The thinking has been that T-cell-mediated inflammation sends the immune system into overdrive, causing the body to attack itself.
MS occurs when this attack targets the protective insulation known as myelin, which protects nerve fibers of the central nervous system. Myelin helps nerve fibers transmit electrical signals.
Instead of targeting T cells, Rituxan targets specific immune cells called B cells.
Studies by the UCSF researchers and others suggest that B cells and related pathways play a key role in destroying myelin.
The study included 104 patients with relapsing-remitting multiple sclerosis treated with either two infusions of Rituxan separated by two weeks, considered one course of treatment, or placebo infusions.
The patients were followed for 48 weeks, and brain imaging was performed to look for areas of inflammatory lesions at weeks 4, 12, 16, 18, and 24.
The imaging revealed dramatic and very rapid improvements in these lesions.
By week 24, the Rituxan-treated patients showed 91% fewer lesions, compared with the placebo-treated patients, and the results were similar at week 48.
"What we found so stunning was not only that the drug worked, but that it worked almost immediately," Hauser says.
The patients who got Rituxan showed improvement in lesions with the first post-infusion MRI scan, taken just weeks after treatment ended.
"This could only have happened if the B cells themselves are the culprit and not the antibody," he says. "It sends us back to the lab to discover what it is about the B cell, independent of its impact on antibodies, that is at the center of what causes MS flares."
Rituxan Safety Concerns
Hauser says there were few treatment-related side effects among the patients in the study, but questions about the long-term safety of Rituxan remain.
Rituxan is approved for the treatment of non-Hodgkin's lymphoma (NHL) and rheumatoid arthritis.
Use of the drug has been linked to a rare but fatal brain infection known as progressive multifocal leukoencephalopathy (PML). But it is not clear if PML is caused by the drug or by the patients' underlying disease.
Until more is known and until Rituxan is approved for the treatment of MS, patients with multiple sclerosis should not use it, says John Richert, MD, the National Multiple Sclerosis Society's executive vice president for research and clinical programs.
"We really want to discourage off-label use," he tells WebMD. "We just don't know enough about its long-term safety."
But Richert agrees that the early findings offer the hope of a new direction in the study and treatment of MS.
"Within the limitations of what you would expect with a small trial of short duration, the (UCSF) results are very exciting," he says. "We are cautiously optimistic that the phase III trials will show the same degree of efficacy."
SOURCES:
Hauser, S.L., The New England Journal of Medicine, Feb. 14, 2008; vol 358: pp 676-688.
Stephen L. Hauser, MD, department of neurology, University of California, San Francisco.
John Richert, MD, executive vice president for research and clinical programs, National Multiple Sclerosis Society.
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