Risk stratification and patient counseling for natalizumab in multiple sclerosis

Natalizumab has demonstrated efficacy in multiple sclerosis (MS), but is associated with increased risk of progressive multifocal leukoencephalopathy (PML), a potentially fatal brain infection caused by the JC virus. At the time of natalizumab's reapproval in 2006, the estimated risk of PML was 1:1,000 (95% confidence interval 0.2–2.80) over 17.9 months of treatment.1 Since then, 3 risk factors for natalizumab-related PML have emerged2: 1) cumulative exposure to natalizumab, with risk increasing up to 3 years, after which risk appears to plateau; 2) previous treatment with cytotoxic or immunosuppressive (IS) drugs3; and 3) prior history of JCV infection, as indicated by the presence of JCV antibodies. Using a 2-step ELISA assay for anti-JCV antibodies, Gorelik et al.4 reported a 53.6% incidence of anti-JCV antibodies in patients with MS; the false-negative rate was 2.5%. To date, 28 natalizumab-related PML cases had blood specimens available 1 year or more prior to the development of PML. Using this assay, all 28 patients were seropositive, which is highly statistically significant ( p = 3.21 × 10−8).5 This assay is now clinically available in the United States …