Risk Factors Predict PML Risk with Tysabri

May 17, 2012 — Tysabri (natalizumab), a multiple sclerosis treatment, has come under scrutiny after it was linked to hundreds of cases of Progressive Multifocal Leukoencephalopathy (PML), a deadly brain disease. Tysabri is thought to cause PML by activating the JC-virus, which is normally dormant.

PML was an exceptionally rare disease before Tysabri. Now, a new study has been published in the New England Journal of Medicine which found that Tysabri patients without the JC-virus had an almost zero risk for developing PML. With the advent of a commercially available test for the JC-virus, more people will be able to be screened for the virus before taking Tysabri.

The researchers analyzed data from 54 patients who had available pre-treatment antibody status. All 54 patients developed PML, and all tested positive for the JC-virus antibodies. The presence of an antibody means that they contracted the virus, and their body created antibodies to defend itself.

Of the nearly 100,000 people who have used Tysabri, approximately 212 have developed PML as of February 29, 2012.

The researchers also identified three risk factors which significantly increase a Tysabri patient’s risk of developing PML. These risk factors include: 1) taking Tysabri for longer than 24 months, 2) testing positive for the JC-virus antibodies, and 3) having a medical history of immunosuppressant therapy.

Among patients who had all of these risk factors, PML occurred in approximately 11.1 per 1,000 patients. Among the patients who had no risk factors or JC-virus antibodies, the risk was approximately 1 per 1,000 patients.

Tysabri has been under regulatory scrutiny since it was approved in 2004. Soon after its approval, patients began suffering from PML. The FDA decided to recall Tysabri in 2005. When the manufacturer developed strict criteria for determining risk factors, the FDA allowed Tysabri back onto the market. Now there is a commercially-available test for the JC-virus. There is also scientific data to back up the rate of PML when the JC-virus is present. Today, doctors are much better-equipped to inform new Tysabri patients of the risk of PML before they prescribe the drug.