The Effect of Ocrelizumab on Anti-JC Virus Antibody Index

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.

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.

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.

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.