ABSTRACT Purpose/Introduction The anti‐JC virus (JCV) antibody index is used to stratify the risk of progressive multifocal leukoencephalopathy (PML) in multiple sclerosis (MS), particularly with natalizumab therapy. B‐cell‐depleting therapies may alter antibody levels and potentially confound the estimation of PML risk. This study evaluated the effect of ocrelizumab on anti‐JCV antibody indices during the first 2 years of treatment. Methods: We conducted a retrospective cohort study of 553 MS patients who initiated ocrelizumab between 2017 and 2019. Anti‐JCV antibody indices were measured using the STRATIFY JCV assay at baseline and approximately every 6 months prior to subsequent infusions. Linear mixed‐effects models were used to assess longitudinal changes in log‐transformed JCV indices, adjusting for age, sex, and ethnicity. Secondary analyses evaluated serum B‐cell counts and immunoglobulin levels. Sensitivity analyses addressed missing data. Results/Finding There was no significant change in anti‐JCV antibody index over time following ocrelizumab initiation (mean percent change per infusion cycle −0.049%, 95% CI: −0.449 to 0.351; p = 0.81). Results were consistent across sensitivity analyses and did not differ by age or sex. In contrast, peripheral B‐cell counts declined significantly after treatment initiation and remained suppressed. Serum IgG, IgM, and IgA levels decreased modestly but significantly over time. JCV seroconversion occurred in 4.1% of initially seronegative patients, while seroreversion occurred in 6.6% of initially seropositive patients. Conclusion: Anti‐JCV antibody indices remain stable during the first 2 years of ocrelizumab treatment despite marked B‐cell depletion and modest reductions in serum immunoglobulins. These findings suggest that existing PML risk stratification tools based on anti‐JCV antibody indices remain applicable during early ocrelizumab therapy.
Virupakshaiah et al. (Fri,) studied this question.