As many of you are aware, Tysabri has become one of the most widely used medications for multiple sclerosis. At this time there are nearly 100,000 people taking Tysabri around the world. In our center in Norfolk we currently are treating approximately 180 patients with Tysabri each month. It has become popular for several reasons, but primarily because it seems to be more effective than anything else on the market at preventing MS relapses and slowing down disability. It is given as an intravenous infusion, which takes 2 hours overall, once a month. It is thought to work by preventing inflammatory cells which cause MS from entering the nervous system.
There have been new developments within the past year which have improved our ability to use this medication safely. Tysabri is very well tolerated by most patients, but there is a small risk that it can activate a viral infection in the brain called progressive multifocal leukoencephalopathy, or PML. PML is caused by activation of a virus called the JC virus. The symptoms may be similar to those of MS itself, but they tend to be more progressive and severe. For example, the early symptoms of PML might include progressive weakness of one side, and enlarging blind spot, difficulty with speech or language, or changes in behavior.
PML is actually not terribly difficult to diagnose. There are characteristic signs on MRI. A spinal tap required because we are able to detect to the viral DNA in the spinal fluid.
The current treatment is designed to restore the immune system to normal. To do that, we removed the Tysabri from the bloodstream using a technique called plasmapheresis. This is basically a blood washing procedure. Blood is removed from a large vein, separated into cells and plasma, and the cells are returned to the body with artificial plasma. The Tysabri therefore is removed with the plasma. The immune system returns to normal and a syndrome called the Immune Reconstitution Inflammatory Syndrome - IRIS for short - usually develops. This is similar to a very severe attack of MS, and is treated with steroids. This can last for a number of months. If all goes well, the patient will recover but will frequently have more disability than they had previously. Some patients do still die from PML, but the percentage is down to under 20% with our current treatments.
Because this is such a potentially serious side effect, researchers have been trying to figure out which patients are most likely to get PML. It turns out that roughly half of the population carries the JC virus in their bodies without knowing it. We now have a blood test which can tell quite accurately whether or not a person carries the virus. If he or she does have the virus, the risk of PML will be higher. If there is no virus present, the risk of PML is extremely low.
The risk of PML also increases the longer you take Tysabri. For the first couple of years, even if you have the virus, the risk is less than 1:1000. After that, for patients with the virus, the risk increases to approximately 1:240. Also, if you have previously been treated with chemotherapy, such as Novantrone, Imuran, methotrexate, or others, your risk is increased.
I realize that some of this sounds a little scary. However, you have to compare the risk of PML to the risk of other treatments for other conditions and indeed to other life events themselves. For example the lifetime risk of dying from fire or smoke is 1:1116; from a car accident, 1:100 (*). Taken in that context, the risk of PML does not seem so bad.
To summarize, Tysabri is a widely used and very effective treatment for multiple sclerosis. While it does carry some risk, we are beginning to learn which risk factors are important so that we can identify patients who are most in danger of getting PML but also we can identify patients who have an extremely low risk and who may benefit from beginning Tysabri earlier in the course of MS.
It now appears that relative risk factors for development of PML include positive JC virus antibody status, duration of treatment, and previous treatment with chemotherapy. Patient’s with those risk factors should certainly keep in close contact with their physicians and frankly discuss their own particular situation with them. Patients who do not have any of those risk factors may be eligible to consider Tysabri early in the stages of MS.
(*) this is from an article by Drs Fox and Rudick in Neurology 2012;78;436