Publication date: May 17, 2019
As Joseph Berger, MD, chief of the multiple sclerosis division in the University of Pennsylvania’s Perelman School of Medicine in Philadelphia, pointed out, it’s not MS per se that puts a patient at risk for PML, the rare but often fatal inflammatory viral disease — characterized by progressive damage or inflammation of the white matter of the brain.
“Although they weren’t used widely in great numbers, they were still used, and we never had a case of PML reported as associated with MS, despite the fact that we gave people cyclophosphamide and azathioprine, and large doses of steroids, and a large variety of other drugs when they had aggressive disease that, in theory, would have put them at risk for developing PML. “
Instead, in MS, PML has been associated with a few disease-modifying drugs, the first being natalizumab (Tysabri).
According to the National Multiple Sclerosis Society, while the vast majority of PML cases in MS involve patients taking natalizumab, cases of PML have since been reported in individuals treated with other agents including dimethyl fumarate (Tecfidera) and fingolimod (Gilenya).
In a 2017 article in Multiple Sclerosis and Related Disorders, Berger divided MS disease-modifying therapies into three classes, depending on the degree of PML risk: As he put it in his article, “natalizumab occupied a place of its own with respect to PML risk,” and was the only drug he assigned to class I. PML is caused by activation of the JC (John Cunningham) virus that, according to estimates, is eventually acquired by more than 70% of the population.
As described by the drug’s manufacturer, a patient’s risk of developing PML is higher if that patient has been infected by the JC virus, has taken natalizumab for a prolonged period of time (especially beyond 2 years), and was previously treated (before natalizumab) with an immunosuppressant.
Researchers have toyed with longer intervals between natalizumab infusions as a means of reducing PML risk while maintaining the drug’s efficacy.
As for the risks associated with class II drug fingolimod, “there is no risk mitigation strategy right now,” said Berger, who added that the risk with fingolimod is “very low” (about one case per 18,000 patients).
“Whether PML will be observed with other [disease-modifying therapies] in use for MS .. . remains uncertain,” wrote Berger in his article.
Berger noted that Spanish researchers have proposed that one such marker — lipid-specific IgM bands in spinal fluid — are associated with a reduced risk of developing PML during treatment with natalizumab.
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