Tysabri PML Risk Factors Outlined in New Study

The findings of new research may make it easier for doctors to identify users of the multiple sclerosis drug Tysabri who are at risk of suffering a rare and potentially life-threatening brain infection, known as progressive multifocal leukoencephalopathy (PML).

In a study published in the New England Journal of Medicine on May 17, researchers associated with Biogen Idec, identified three risk factors for developing PML from Tysabri.

PML is a rare and deadly brain infection that is believed to be caused when some immunosuppressant drugs, like Tysabri, disable the immune system enough for the JC virus to take hold.

Tysabri (natalizumab) is an intravenous injection given every 28 days to treat multiple sclerosis (MS) and Crohn’s disease. Manufactured by Biogen Idec Inc. and marketed with Elan Corp PLC, Tysabri has been shown to prevent relapse, cognitive decline and vision loss associated with MS.

Shortly after Tysabri was introduced in 2004, it was recalled after cases of PML were identified, including at least two deaths. The medication was re-introduced in 2006, with stricter guidelines for usage and more prominent warnings about the possible PML risks associated with Tysabri.

In the new study, researchers looked at 54 of the 212 confirmed cases of PML that have been identified, out of the nearly 100,000 patients treated with the drug. All of the cases involved users who tested positive for anti-JC virus antibodies before they began taking Tysabri, meaning the virus was likely present but dormant. The risk of developing PML was lowest among those patients who tested negative for the antibodies before taking Tysabri.

Researchers indicate that the presence of anti-JC virus antibodies, prior use of immunosuppressant drugs and increased duration of the use of Tysabri were all risk factors that could be used to help doctors determine the likelihood of developing PML.

The findings are similar to those determined by the FDA earlier this year. The FDA has identified three risk factors that increase the odds of a Tysabri patient developing PML:

• The presence of anti-JCV antibodies, which indicate that the JC virus is present in the body
• Treatment with Tysabri for longer than two years
• Treatment with other immunosuppressants before being placed on Tysabri

Patients with all three risk factors appear to have the highest chances of being diagnosed with PML, the FDA determined.