Multiple Sclerosis and Progressive Multifocal Leukoencephalopathy: Risks and Detection

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Fred Lublin, MD, explains that prior to the use of natalizumab, progressive multifocal leukoencephalopathy (PML) had never been observed in patients with multiple sclerosis (MS). Providing accurate figures about the risk of PML to patients who may be or are being treated with natalizumab iscritically important in makingthe best treatment choices. PML is not as severe and lethal in the setting of MS as in other diseases, such as HIV. Still, he adds,PML often leaves individuals left with some kind of disability, and the mortality rate in MS is about 20%.

Patricia K. Coyle, MD, lists the 3 major risk factorsrecognized as contributing to the development of PML in MS.The first and requisite factor is JC virus—positive status. JC virus is a ubiquitous yet benign virus. Approximately 55% of the general population will test positive for the antibody.A simple blood test can be used to determine JC virus status.

The second risk factor is the duration oftreatment on natalizumab. Less than 2%ofPML cases in MS have been documented in JCvirus—positive patients on treatment for less than 1 year.The greatest risk is present in JC virus–positive patients on treatment for more than 2 years,and the risk is thought to increasethe longer treatment it is continued.

Finally, a history of prior immunosuppression will put JCvirus—positivepatients on natalizumab at an increased risk for PML. This includes the use of various immunosuppressive therapies such as azathioprine, methotrexate, and cyclophosphamide.

More recently, Coyle explains, data have shown that the risk of developing PML may also vary based on JC virus antibody index, a measure of the plasma anti-JCV antibody levels. For example, if the JC virus antibody index is ≤0.9, conveying a lower antibody titer, a patient is at much lower risk of PML. In contrast,if the JC virus antibody index is >1.5, a patient is at higher risk. [Plavina T, et al. Ann Neurol. 2014;76(6):802-812.]