Tuesday, January 24, 2012

FDA updates Tysabri label to include testing for PML risk

Julie Stachowiak, PhD 
Writer, ms.about.com

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.


  1. I, for one, am happy for more knowledge. I have been on Tysabri for 4 yrs (#51 this month) now and tested positive for the JC virus several months ago. For me, this means I am in power to make more informed decisions with my choice of continuing my Tysabri treatment. My Dr. and I are both more aware of what we are dealing with. I am so thankful for your blog that is loaded with information. KNOWLEDGE IS POWER!!!

  2. I, have been on Tysabri for about 2 1/2 yrs. Was tested positive for the JC virus last June 2010. My doctor and I have discussed this fact in detail and we both decided that my positive results of treatment out way the chances of developing PML. I agree with Katehirth "KNOWLEDGE IS POWER".

  3. My wife, Dr.Natalie Murphy, is one of the now 201 people diagnosed with Tysabri related PML. Two years on from the diagnosis, she is in a paraplegic state and is unable to speak. Despite this, she is continuing to be an inspiration to us all. More information can be found at www.defernotrust.org

  4. I have been on Tysabri Since December 2009 and have received so far a total of 25 infusions. I just had the blood work done to test for the JC virus. I am awaiting the results right now. I am rattled by the idea of PML being a real issue. In speaking to my neurologist I realized that everyone who are taking this drug are basically human guinea pigs. I mean yes it is known,PML is a real risk and has been known for some time now but only after the drug has been prescribed for many MS patients have they found another real risk from Tysabri. IRIS, is another abbreviation that is another serious abbreviation that needs to be considered before going on this therapy. If I would have known about all of these possible issues before starting I wouldn't have agreed to take Tysabri. There are enough things that need to be seriously thought of once being diagnosed with MS which can cause a great deal of stress. All that I am saying is that hindsight is 20/20.

    1. I am interested to know what IRIS is? Please enlighten me.

    2. This comment has been removed by the author.

    3. This comment has been removed by the author.

    4. This comment has been removed by the author.

  5. Wow! Thank you for the heads-up, Riseski!
    I have been diagnosed with MS for coming up on 3 years now. Was doing well until 3 months ago when I had a particularly nasty relapse. Due to this relapse 2 specialists have recommended I start Tysabri. I am currently awaiting results of my JC virus test.
    I was aware of the risk of PML, but had never heard of IRIS. After doing some searching, I learned that IRIS is "Immune Reconstitution Inflammatory Syndrome". This is basically an inflammatory condition that results as the immune system "reconstitutes" (or rebounds) after stopping therapy with Tysabri. The prescribing information for Tysabri indicates that IRIS is only seen after patients are taken off Tysabri after suffering from PML. However, a recent study in Archives of Neurology (http://archneur.ama-assn.org/cgi/content/short/68/2/186) seems to suggest otherwise.
    I think the lesson is that those of us with MS who are considering starting Tysabri need to add IRIS to the list of topics that must be discussed with our specialist in order to make an informed decision.