Objectives This study sought to evaluate rates of anti-JCV antibody seroconversion and prospective change in antibody titre in a cohort of people with MS receiving natalizumab.

Methods Anti-JCV antibody results (n=1154) from the second-generation STRATIFY JCV™ DxSelect™ test were analysed from an observational cohort of MS patients on natalizumab (n=485; n= 340 with repeat testing).

Results At baseline, 59% (287/485) of patients were JCV seropositive; 33% (162/485) had a high anti-JCV antibody index (> 1.5). Baseline titres and rates of seropositivity increased slightly with baseline patient age. With multiple tests repeated over time, 22.3% of seronegative patients converted to seropositive. When comparing pairs of prospective tests, seroconversion rate was greater than seroreversion rate (40/373 (10.7%) vs 18/296 (6.1%); p<0.05). Moreover, anti-JCV antibody titres increased across prospective paired tests (mA-B 0.095; paired t(668)=4.6; p<0.0001) – an effect that was independent of baseline sample titre. This magnitude of antibody level increase far exceeds that expected due to age alone.

Conclusions Our data suggest that natalizumab therapy itself causes anti-JCV antibody titres to increase over time. Future work should investigate the underlying mechanisms, and clinical relevance to risk stratification of this phenomenon.