March 1, 2006 — -- Tysabri, a medication that treats the symptoms of the autoimmune disease multiple sclerosis, may offer new hope for patients, but it also carries small life-threatening risks, according to three new studies published in this week's New England Journal of Medicine.
Multiple sclerosis, or MS, affects approximately 400,000 Americans, mostly young adults. While the cause is unknown, MS can lead to serious nervous system damage. The debilitating symptoms, such as numbness and muscle weakness, often get worse over time, and current medications are not always completely effective in treating it.
That's why researchers and patients were so interested in Tysabri, which came on the market several years ago and was sold by Biogen Idec and Elan Pharmaceuticals. Clinical trials showed that it could alleviate symptoms.
However, last February two patients developed a rare viral infection while taking the drug, and one of these patients died. As a result, the manufacturers removed Tysabri from the market so the risks could be investigated.
The new studies released today shed new light on how the drug helps MS patients, and how often it may cause serious side effects. The studies are likely to become a major topic of discussion next week when a U.S. Food and Drug Administration committee meets to discuss using Tysabri to treat patients with relapsing forms of multiple sclerosis.
The first study looked at more than 940 MS patients, about 600 of whom took Tysabri and the others a placebo. The patients on Tysabri showed improvement in their symptoms, and none developed progressive multifocal leukoencephalopathy, or PML, the disease that killed the MS patients when Tysabri was on the market. PML is a rare but often fatal viral disease of the nervous system.
However, in an additional study, PML did strike two patients. This study followed 1,171 MS patients who showed symptoms despite treatment with interferon, another MS medication. In this study, half of the patients took Tysabri and interferon, while the other half received a placebo and interferon. This trial also showed that Tysabri improved symptoms.
PML is linked to a virus that causes destruction of the protective covering of nerve fibers in the brain. Many people are exposed to the virus in childhood, but it tends to come out of dormancy only among those with weakened immune systems, according to the FDA. There is no cure, and people with PML usually die one to four months after its onset.
Knowing this risk, the researchers of the third published study attempted to find other potential cases of PML among the approximately 3,000 patients who received Tysabri in clinical trials. But no other cases were found, meaning that roughly one person out of every 1,000 who took this drug in clinical trials developed the disease.
Because of the new data, the FDA will make recommendations next Tuesday and Wednesday on whether Tysabri should be returned to the market and become available for use outside of clinical trials.
A doctor with the National Multiple Sclerosis Society said his organization did not have an opinion on whether the FDA should approve Tysabri but instead provided information to help the agency make a decision.
"Our feeling has been that our role is to do everything we can to make sure that the FDA gets all the information it needs to make the wisest decision possible," said Dr. John Richert, the society's vice president for research and clinical programs.
Tysabri is a "significant advance" for MS patients, said Dr. Allan H. Ropper, author of an editorial that accompanied the studies published in The New England Journal of Medicine. He is chairman of the department of neurology at Caritas St. Elizabeth's Medical Center and chairman and professor of neurology at Tufts New England Medical Center in Boston.
Dr. Richard Rudick, the lead author of one of the studies, agreed.
"In the studies there were significant improvements in self-reported symptoms, which we have never seen in previous studies," said Rudick, of the Mellen Center for MS Treatment and Research at the Cleveland Clinic Foundation.
Still, the potential benefits of Tysabri need to be weighed against the potential risk of acquiring PML and other side effects associated with the medication, experts said.
"A lot of these patients don't realize what PML is," said Dr. Syed Rizvi, the director of the Rhode Island Hospital Multiple Sclerosis Center in Providence. "I don't think they will be too excited about Tysabri once they realize the risk of PML."
And there are additional risks associated with the medication, said Dr. Thomas Leist, director of the Comprehensive Multiple Sclerosis Center at Thomas Jefferson University in Philadelphia.
"What nobody talks about is that there is a small but not insignificant risk of increased infections -- this is concerning in patients with advanced MS who are at increased risk of acquiring infections," he said.
So, patients eager to try Tysabri if it is returned to the market will need to discuss and consider carefully the potential risks and benefits of using the medication, Rudick said.
"At the moment we have a large pool of MS patients who are not controlled with current drugs, and I think those patients are prime patients to [start taking] Tysabri if the FDA releases the drug, " he said. "But they would need to be well-informed of the risk and willing to accept this risk."
Schofer is a chief resident in emergency medicine at the U.S. Naval Medical Center in San Diego. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.