High cumulative JC virus seroconversion rate during long-term use of natalizumab.

Background and purpose John Cunningham virus ( JCV) seropositivity is a risk factor for the development of natalizumab-associated progressive multifocal leukoencephalopathy ( PML) in multiple sclerosis ( MS) patients. When JCV seronegative patients seroconvert, their risk of developing PML increases. Limited longitudinal data exist about the seroconversion rate amongst natalizumab-treated relapsing−remitting MS ( RRMS) patients. Our objective was to evaluate the seroconversion rate in a large Dutch cohort of natalizumab-treated RRMS patients. Seroconversion was defined as at least two consecutive seropositive serum samples (or cessation of therapy after a single seropositive sample because of seropositivity) after initial seronegative testing. Methods and results In our study of 179 patients for whom longitudinal blood samples were available over a long period (median 4.2 years), anti- JCV antibody indices were measured in 933 available samples. Eighty-six patients (48.0%) tested seronegative initially. Of these 86 seronegative patients, 23 patients (26.7%) seroconverted during follow-up. The annualized seroconversion rate was 7.1%. Seroconversion occurred between 9 and 90 months (median 43 months) of treatment. The rate of seroconversion was independent of follow-up duration. No significant increase was seen in the anti- JCV antibody index in the non-converting patients during the follow-up. Conclusion The annualized seroconversion rate of 7.1% in patients using natalizumab, cumulatively leading to more than 25% of seronegative patients becoming seropositive in 4 years, is of clinical relevance and should be taken into account in the risk assessment when considering the start of natalizumab therapy. [ABSTRACT FROM AUTHOR]