Risk for PML in Multiple Sclerosis Predicted With Anti-JCV Antibody Index

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While an efficacious treatment for relapsing MS, natalizumab is associated with risk of developing progressive multifocal leukoencephalopathy.
While an efficacious treatment for relapsing MS, natalizumab is associated with risk of developing progressive multifocal leukoencephalopathy.

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.”

Reference

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.

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