The FDA approved Tysabri in November 2004 to treat relapsing forms of multiple sclerosis (MS). On Feb. 28, 2005 Tysabri was suspended over cases of a rare, disabling neurological disease called PML in patients taking Tysabri.
In February 2006 the FDA allowed Tysabri's clinical trials for MS treatment to resume. However, the drug isn't back on the market.
PML, or progressive multifocal leukoencephalopathy, affects the central nervous system, usually in people with unhealthy immune systems. PML is caused by a common virus, but most people with the virus don't get PML.
Now, researchers say they've found no new cases of PML in more than 3,000 patients who took Tysabri in the drug's clinical trials. Their report appears in The New England Journal of Medicine.
Combing the Records
The researchers did a detailed review of 3,116 patients who took Tysabri in clinical trials. Most patients had gotten nearly 18 monthly doses of the drug. The patients either had MS, Crohn's disease, or rheumatoid arthritis. Before its suspension, Tysabri was being studied as a possible treatment for Crohn's disease and rheumatoid arthritis.
A total of 44 patients were referred to experts to check for possible PML. All but one of those patients turned out not to have PML. Complete data wasn't available for the one exception, so PML wasn't confirmed in that person, either.
The only confirmed cases of PML in people taking Tysabri are the three cases that had previously been reported, according to the review.
The review had three key findings:
- The group had no new cases of PML.
- About one in 1,000 trial participants who took Tysabri for 18 months got PML.
- PML risk beyond 18 months isn't known.
The researchers included Tarek Yousry, Dr.Med.Habil., who works in London's Institute of Neurology.
"This study was designed to address a critical, immediate need for patient safety in the people who participated in clinical trials of this drug," researcher Eugene Major, PhD, says, in a news release.
"We had to assess who else might be at risk," says Major, who works at the National Institute of Neurological Diseases and Stroke (NINDS), part of the U.S. National Institutes of Health.
The researchers caution that they don't know if any of the patients will develop PML later on.
They add that their review didn't include everyone who ever took Tysabri. But PML is "generally a serious, disabling disease," and would likely have been detected, the researchers note.
"It seems that less than two years of treatment with [Tysabri] alone is relatively safe, but the possibility remains that PML will develop in one in 1,000 patients," states an editorial in the journal.
"At the moment, it is doubtful that neurologists will chance using [Tysabri] in conjunction with other immunosuppressive agents, with the possible exception of corticosteroids when they are required for acute relapses," the editorial continues.
The editorial was written by Allan Ropper, MD, of the neurology department at Boston's Caritas St. Elizabeth's Medical Center.