Incidence Of PML With Tysabri In Multiple Sclerosis Lower Than Previously Thought

Main Category: Multiple Sclerosis
Also Included In: Neurology / Neuroscience
Article Date: 08 May 2009 - 3:00 PDT

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The risk of developing progressive multifocal leukoencephalopathy (PML), a viral brain infection, in patients with multiple sclerosis (MS) taking the drug natalizumab (Tysabri) appears to be much lower - and the infection less deadly - than previously estimated, according to new postmarketing surveillance data.

Previous research found that the risk of developing PML was 1 in 1000, but new data show that the risk is closer to 1.2 per 10,000 patients, according to Carmen Bozic, MD, vice president and global head of drug safety and risk management for the maker of natalizumab, Biogen Idec, in Cambridge, Massachusetts.

Dr. Bozic delivered an updated overview of the risks and benefits of natalizumab during the American Academy of Neurology (AAN) 61st Annual Meeting.

Approved In 40 Countries

Natalizumab is approved in over 40 countries for the treatment of relapsing forms of MS to reduce the frequency of relapses and delay worsening of physical disability in patients who have had an inadequate response to or are unable to tolerate another MS medication. The drug is approved in the United States, Canada, Europe, Australia, and parts of the Middle East and Latin America. It is also approved in the United States to induce and maintain clinical response and remission in adult patients with moderately to severely active Crohn's disease.

Natalizumab is an antibody rather than an interferon; Biogen Idec also manufactures an interferon beta1-a drug (Avonex) for newly diagnosed MS patients. It works by preventing white blood cells from entering the brain and attacking nerves.

The data presented were taken from the Tysabri Outreach: Unified Commitment to Health (TOUCH) prescribing program and the Tysabri Global Observation Program in Safety (TYGRIS), both part of a global risk-management program to further evaluate the safety of natalizumab. TOUCH is a mandatory prescribing program for all patients, physicians, and infusion centers in the United States that ensures "appropriate and informed use of natalizumab," the researchers note. TYGRIS is a global voluntary observational study evaluating the long-term safety of natalizumab in clinical practice. Data from countries that do not participate in either TOUCH or TYGRIS were also collected.

As of the end of March 2009, or about 3 years after approval in the United States and the European Union, approximately 52,000 patients had been treated with natalizumab in the postmarketing setting. "This is more than 10 times the exposure we had in clinical trials," said Dr. Bozic.

Long-Term Exposure

As well, there is now much more information on the drug's long-term exposure in the postmarketing setting, she said. To date, about 24,900 patients have been taking the drug for 12 months or longer, 14,400 for 18 months or longer, and 6800 for 24 months or longer. Some patients have taken the drug for more than 2.5 years, she added.

"So both overall exposure and long-term exposure is significantly greater than we had in the original clinical trials, and that gives us a very robust ability to evaluate the safety of the drug," she told Medscape Neurology & Neurosurgery.

Of the 52,000 patients who have taken the drug, there have been 6 cases of PML, or an incidence of approximately 1.2 per 10,000 patients treated. "It's trending lower than what we saw in the clinical-trial setting," said Dr. Bozic.

The 6 patients - 3 men and 3 women aged 37 to 59 years - had taken the drug as monotherapy for periods ranging from 12 to 31 months. "This is a highly variable duration of treatment," noted Dr. Bozic.

Helen Yates, Chief Executive of the Multiple Sclerosis Resource Centre said, "It is obviously good news to see that the incidence of PML looks much lower than was first supposed. We would still like to see more investigation into the potential causal links between Tysabri and PML and of course the potential to develop this life-threatening condition does still remain"

Source
American Academy of Neurology

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