Anti-JCV antibody index assessment may improve risk prediction for progressive multifocal leukoencephalopathy (PML) in people with multiple sclerosis (MS) treated with natalizumab, according to findings from a pooled analysis published in the Lancet Neurology.
Investigators pooled patient-level risk factor data from 4 observational, open-label studies (STRATIFY-2, STRATA, TOP, and TYGRIS) to determine risk estimates for PML in subjects with MS who had previously been treated with natalizumab (n=37,249). Additionally, researchers analyzed data to establish risk for PML by analyzing serum concentrations of anti-JCV antibodies.
Only 0.4% of patients in this cohort (n=156) had a PML diagnosis. Of 120 patients who had anti-JCV antibody test results available, approximately 99% (n=119) tested positive for the antibodies 6 months prior to a PML diagnosis. In the overall cohort, antibody-positive patients treated with natalizumab who also had previous immunosuppressant exposure over a 6-year period had a probability of PML developing of 2.7% (95% CI, 1.8-4.0), whereas those without immunosuppressant exposure had a probability of 1.7% (1.4-2.1).
Those who tested negative for anti-JCV antibody had an estimated PML risk of <0.07 per 1000 patients (95% CI, 0.00-0.40). In addition, the annual estimated PML risk per 1000 patients among subjects without a history of immunosuppressant exposure, no previous PML diagnosis, and an anti-JCV antibody index of ≤0.9 was between 0.01 (0.00-0.03) at 1 year (1-12 infusions) and 0.6 (0.0-1.5) at 6 years (61-72 infusions).
This pooled analysis included a small number of patients with immunosuppressant exposure and duration of treatment >5 years, resulting in wide variability of risk estimates in this population group. According to the investigators, this may explain why risk estimates were lower at 6 years (infusions 61-72) vs those at year 5 (infusions 49-60).
Despite this potential limitation, the investigators believe their findings may ultimately improve “the temporal precision of natalizumab-associated PML risk estimates and address the shift in clinical practice away from assessing binary antibody status (ie, anti-JCV antibody negative or positive) toward assessing anti-JCV antibody index as a PML risk variable.”
Ho PR, Koendgen H, Campbell N, Haddock B, Richman S, Chang I. Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol. 2017;16(11):925-933.