Antibody Test Identifies New Risk Factor for PML

On January 20, 2012, the United States Food and Drug Administration (FDA) announced that three factors are now identified with increasing the risk of Progressive Multifocal Leukoencephalopathy (PML) for individuals with multiple sclerosis (MS) being treated with Tysabri® (natalizumab). PML is a potentially fatal brain infection with the JC virus (JCV), in people with weakened immune systems. The FDA has approved a labeling change, which adds the results of a newly approved test for the presence of anti-JCV antibodies, to the two previously listed risk factors. The following three PML risk factors now appear on Tysabri’s labeling:

  • The presence of anti-JCV antibodies, which identifies a previous exposure to the JC virus
  • Longer duration of Tysabri treatment, especially after two years
  • Prior treatment with an immunosuppressant medication, such as mitoxantrone (Novantrone®), azathioprine (Imuran®), methotrexate, cyclophosphamide (Cytoxan®), or mycophenolate.

Each of these three factors increases the PML risk and the combination of all three increases the risk to as high as 11 in 1,000 (or slightly more than one percent). The new validated JCV antibody detection test (Stratify JCV Antibody ELISA test) was cleared by the FDA on January 20, 2012 and is now commercially available from Quest Diagnostics. Through this specific testing, JCV antibodies have been measured and validated in 59,000 tests. A positive test indicates a previous JCV exposure, but does not indicate the development of PML. According to the FDA, “The test is for professional use and by prescription only and is to be performed only at Focus Diagnostics’ Reference Laboratory [a wholly owned subsidiary of Quest Diagnostics Incorporated].”

JCV typically remains dormant in those exposed to the virus, but may become active when the immune system is weakened. An individual needs to be anti-JCV antibody positive in order to be at risk of developing PML, although a person who is negative could be exposed to the virus at any time. Whether or not a person has received any prior treatment for their MS, about 55 percent of individuals with MS are anti-JCV positive.

The new labeling explains that “The risks and benefits of continuing treatment with Tysabri should be carefully considered in patients who are found to be anti-JCV antibody positive and have one or more additional risk factors. Patients who are anti-JCV antibody negative are still at risk for the development of PML due to the potential for a new JCV infection or a false negative test result. Therefore, patients with a negative antibody test result should be retested periodically.”

For more information on this label change, please refer to the FDA announcement.

Readers may also contact MSAA’s toll-free Helpline at (800) 532-7667 to speak with a consultant.

Written by Jack Burks, MD, MSAA Chief Medical Officer &
Susan Wells Courtney, MSAA Senior Writer and Creative Director