More uncertainty for MS patients taking Tysabri

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When Tysabri first came on the market in 2004 to treat multiple sclerosis, patients hailed it as a wonder drug. Clinical trials showed that it was twice as effective as other medications at preventing recurrences of MS. It also appeared to slow the overall course of the disease.

But it was pulled from the market in 2005 because it caused a rare and sometimes fatal disease called multifocal leukoencephalopathy – PML for short – in two MS patients. MS and PML are diseases involving demyelination of nerve cells, but they had never been seen in the same patients until Tysabri came along. (Typically, PML strikes people with AIDS, transplant patients, and others with compromised immune systems.) Experts at the National Institutes of Health calculated that the chances that an MS patient would develop PML while taking Tysabri were 1 in 1,000.

Pleas from MS patients prompted the FDA to reconsider its decision, and in 2006 it was allowed back on the market. The agency instituted restrictions aimed at reducing the 1-in-1,000 risk. Tysabri is now considered a medication of last resort, and MS patients who take it are monitored for symptoms of PML.

So, has Tysabri – known generically as natalizumab – gotten safer? Not really, according to a series of reports published online today in the New England Journal of Medicine.

The companies that make and market the drug – Biogen Idec and Elan – say that approximately 20,000 MS patients have received monthly Tysabri infusions for at least 18 months since it went back on the market three years ago.

In that time, there have been 12 new cases of PML in MS patients, according to one of the reports, by Eugene Major of the NIH’s National Institute of Neurological Disorders and Stroke. On average, a new case of PML has emerged about once every three months. That works out to an incidence rate approaching 1 in 1,000, Major writes.

And more cases are sure to emerge. The first symptoms of PML aren’t apparent until after patients receive many rounds of treatment. In one case report published today, an MS patient showed signs of PML after 12 doses of the drug. In another case report, symptoms emerged after 14 doses.

Researchers are looking for ways to spot PML as early as possible. A study published as part of the New England Journal’s package found that many MS patients taking Tysabri have elevated levels of JC virus– which causes PML – in their urine and blood.

That’s an encouraging development, but still leaves many questions unanswered. For instance, no one yet knows how JC virus leads to PML. Roughly one-third of healthy adults are thought to carry JC virus in a dormant state and never develop the disease. None of the 19 MS patients tracked in the study developed PML.

The authors of the study said their results are too preliminary to offer meaningful guidance to MS patients. Patients should continue to weigh the risks and benefits with their doctors before deciding whether to take the drug, they said.

-- Karen Kaplan