Stopping Tysabri treatment in multiple sclerosis: disease on the rebound.

Many moons ago it would have been unthinkable that MS treatment would take about 2-3 hours a month. It would have been impossible to imagine that you could simply turn up to your local hospital, have an infusion while you read a book and then tell the ward staff that you would see them again in 4 weeks. This pipe dream became reality with the advent of Tysabri (natalizumab), a monoclonal antibody that has proven to be highly effective in reducing inflammatory activity in MS. Some of my MS patients who are on Tysabri say that they forget for most of the month that they actually have MS. That really says it all. From a scientific perspective, there has been a recent paper in JNNP that provides data on the safety and tolerability of this drug in a large cohort of patients http://jnnp.bmj.com/content/early/2014/02/14/jnnp-2013-306936.abstract?sid=8e3fc276-adf8-49ab-a852-1deb37906d4b . That study also confirms just how incredibly effective Tysabri can be in treating MS.

However, it hasn’t all been sweet sailing for this drug. There was a period when Tysabri’s prospects looked less than rosy, following the discovery that treatment with this drug could lead to activation of a potentially lethal virus, the John Cunningham or JC Virus. Following the discovery of the first few cases in 2006, many hundreds of patients have developed progressive multifocal leucoencephalopathy (PML), a brain infection caused by JC virus. While early cases of PML due to Tysabri were fatal, more recent attempts at doctor and patient education are helping to improve outcomes in patients who develop this complication. We now also have the means to screen patients for prior JC virus infection using an antibody test. A large proportion of the population have had prior exposure to the virus, usually manifesting as a flu-like illness. Once a person has been exposed, the virus remains dormant in the kidneys and can reactivate, especially when the immune system is suppressed.

For patients who are on Tysabri, a positive JC virus test does not mean that PML will develop, but it places patients in a high risk group. In these situations, many will need to stop Tysabri after ~2 years of treatment, the time period after which PML risk rises. The problem is that Tysabri is very effective at controlling MS disease activity and cessation of this medication may lead to worsening of MS symptoms, even if an alternative drug is introduced.

In this issue of the journal, Gueguen and colleagues from Paris provide us with interesting data on exactly how patients fare after Tysabri has been ceased http://jnnp.bmj.com/content/85/9/1038.abstract . While decisions regarding cessation need to be made on a case-by-case basis, the study helps inform clinical decisions making in what is a particularly difficult and frequent problem in MS clinics around the world.

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