Abstract
OBJECTIVE: The increased risk of progressive multifocal leukoencephalopathy (PML) with natalizumab treatment is associated with the presence of anti-JC virus (JCV) antibodies. We analyzed whether anti-JCV antibody levels, measured as index, may further define PML risk in seropositive patients. METHODS: The association between serum or plasma anti-JCV antibody levels and PML risk was examined in anti-JCV antibody-positive multiple sclerosis (MS) patients from natalizumab clinical studies and postmarketing sources. For PML and non-PML patients, the probabilities of having an index below and above a range of anti-JCV antibody index thresholds were calculated using all available data and applied to the PML risk stratification algorithm. Longitudinal stability of anti-JCV antibody index was also evaluated. RESULTS: Anti-JCV antibody index data were available for serum/plasma samples collected >6 months prior to PML diagnosis from 71 natalizumab-treated PML patients and 2,522 non-PML anti-JCV antibody-positive patients. In patients with no prior immunosuppressant use, anti-JCV antibody index distribution was significantly higher in PML patients than in non-PML patients (p < 0.0001). Among patients who were anti-JCV antibody negative at baseline in the AFFIRM and STRATIFY-1 trials, 97% remained consistently negative or below an index threshold of 1.5 over 18 months. Retrospective analyses of pre-PML samples collected longitudinally from PML patients displayed sustained higher anti-JCV antibody index over time. INTERPRETATION: Anti-JCV antibody levels in serum/plasma, measured as index, may differentiate PML risk in anti-JCV antibody-positive MS patients with no prior immunosuppressant use. Continued evaluation of anti-JCV antibody index and PML risk is warranted.