Objectives: To examine the association between JCV Ab index (JCV antibody level as measured using the STRATIFY JCV DX Select assay) and PML risk in natalizumab-treated MS patients.
Methods: JCV Ab index data from JCV Ab+ MS patients enrolled in clinical studies or from postmarketing settings were used for analyses. An analysis of cross-sectional JCV Ab index data from patients without PML was first performed to assess potential relationships between JCV Ab index and current risk factors (natalizumab treatment duration ≤24 vs >24 infusions and prior IS use). P values were calculated using a Wilcoxon rank sum test. The association between JCV Ab index and PML was then assessed using all available longitudinal data. Odds ratios (ORs) were estimated from generalized estimating equations with a logit link. The predicted probabilities were then used to update the current PML risk estimates for JCV Ab+ patients with high/low Ab index by applying Bayes theorem.
Results: JCV Ab index data were available from 71 natalizumab-treated PML patients at least 6 months prior to PML diagnosis and from 2522 non-PML JCV Ab+ patients. JCV Ab index was not found to be associated with duration of natalizumab treatment (P=0.39) or prior IS use (P=0.43), but was significantly associated with PML risk (P<0.001). Estimated ORs were at least 4 for high versus low index in JCV Ab+ patients. Updated PML risk estimates and longitudinal stability of JCV Ab index will be presented.
Conclusions: Risk of PML in JCV Ab negative MS patients is very low (0.1 per 1000). JCV Ab+ MS patients who have low JCV Ab index have several-fold lower PML risk compared with current risk attributed to all JCV Ab+ patients. Utilization of JCV Ab index allows for further clinically meaningful stratification of PML risk in JCV Ab+ natalizumab-treated MS patients.