Abstract
When an infectious serious adverse event is linked with a therapy for an underlying disease, it usually is seen in a few weeks or months, not years. This is not the case with the effective monoclonal antibody therapy for patients with multiple sclerosis (MS) natalizumab (Tysabri), the α4 integrin inhibitor preventing inflammatory T cells entering the brain. The infectious adverse event in patients with MS is another demyelinating disease, progressive multifocal leukoencephalopathy (PML), caused by lytic infection of oligodendrocytes with JC virus (JCV), a ubiquitous agent in the population. Although cases of PML are seen in patients with MS after receiving as few as 7 monthly doses, the highest incidence of PML, 1/75 or higher,1 occurs after 24 monthly doses. Other risk factors for PML in these patients implicate prior exposure to JCV infection evidenced by presence of antiviral antibody as well as previous immunosuppressive treatments.2
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