FDA updates Tysabri label to include testing for PML risk

The US Food and Drug Administration just approved a labeling change to Tysabri (natalizumab), which states that people who test positive for JC virus antibodies are at higher risk of progressive multifocal leukoencephalopathy (PML) if they take Tysabri.

I should start by mentioning that the scientific community has been studying the predictive ability of JC antibodies to indicate that people with a positive test are at an increased risk for PML, however, the test only recently became commercially available. There is now a new lab test from Quest Diagnostics, called STRATIFY JCV.
What does this mean and why is it relevant? Well, this means that doctors and people with MS can now make more informed decisions about Tysabri than before.
JC virus is the infectious agent that causes PML, a potentially fatal brain disease. However, many people in the world have been infected with the JC virus. The virus does not appear to cause any disease in people unless conditions are "just right." In a small percentage of people who take Tysabri (and a few other medications), conditions will be just right for the JC virus to proliferate and cause PML, as certain immune cells that usually keep this virus in check can become depleted.
Since PML cannot develop unless a person has been infected with the JC virus, one approach to preventing PML in people who are taking or considering Tysabri is to test for JC virus antibodies in their blood. In one study, an antibody test successfully identified JC virus antibodies in 100% of samples of people with Tysabri-related PML.
The challenge here is that many, many more people have been infected with the JC virus in their lives than will ever develop PML, even among those who take Tysabri. In fact, one study conducted in Sweden showed that 61% of people with MS tested positive for antibodies to the JC virus – a huge percentage, considering that less than .002% of people on Tysabri ever develop PML. The test is pretty effective if the idea is to prevent all cases of PML by refusing to give them Tysabri, but that approach does exclude many people who would be eligible for Tysabri (and may never develop PML).
Also, a negative test for JC virus antibodies does not mean that the person is at NO risk of PML, as they can become infected with JC virus in the future or have a “false positive” test that incorrectly suggests they have not been infected.
Let's take a look at risk levels for PML, based on the JC antibody test and other risk factors:
  • The risk of people who test positive for JC virus antibodies (with no other risk factors) is less than 1/1000. 
  • If a person tests positive for JC virus antibodies AND has taken Tysabri for more than 2 years AND has previously taken an immune-suppressing drug (such as mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate mofetil), their risk of PML is 11/1000. Before anyone panics, however, keep in mind that even with all of these risk factors, this represents a 1.1% chance of developing PML – or about one in one hundred. People who meet all of these criteria and are taking Tysabri should not assume that they will develop PML, but should carefully consider this information about elevated risk. 
Bottom Line 
My goal here is to help people make rational decisions about treatment, not to sell Tysabri and not to discourage anyone from taking it. The STRATIFY JCV test will give people more information to enter into their personal treatment equation. Some people with a positive test will decide that the benefits of Tysabri warrant the risk of PML. Other people, even with a negative test, will still decide that Tysabri is not the drug for them, as a risk for PML will still exist. It is a very personal decision, based on many factors.
People with MS and their doctors should take a positive JC virus antibody test as just one piece in the whole equation, especially if other therapy options have been explored and failed. A careful risk-benefit analysis with their doctor will help people figure out whether or not Tysabri is right for them.
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Julie Stachowiak, PhD

Julie is the author of the Multiple Sclerosis Manifesto, the winner of the 2009 ForeWord Book of the Year Award in the Health Category. She is an epidemiologist who is also a person living with MS, Julie has an in-depth understanding about current research and scientific developments around MS. She also has first-hand knowledge of the frustrations and anxiety surrounding the disease, as she had MS for at least 15 years before receiving a diagnosis in 2003 and has had several relapses since her diagnosis.