DX51 JCV Antibody Index Stratifies PML Risk in Natalizumab-Treated MS Patients

Thursday, May 30, 2013
Tatiana Plavina, PhD , Biogen Idec Inc., Weston, MA
Meena Subramanyam, PhD , Biogen Idec Inc., Weston, MA
Gary Bloomgren, MD , Biogen Idec Inc., Weston, MA
Sandra Richman, MD, MPH , Biogen Idec Inc., Weston, MA
Amy Pace, ScD , Biogen Idec Inc., Weston, MA
Sophia Lee, PhD , Biogen Idec Inc., Weston, MA
Brian Schlain, MS , Biogen Idec Inc., Weston, MA
Denise Campagnolo, MD , Biogen Idec Inc., Weston, MA
Barry Ticho, MD, PhD , Biogen Idec Inc., Weston, MA

Background: The presence of anti-JCV antibodies (JCV Ab+), prior use of immunosuppressants (IS), and increased duration of natalizumab treatment, especially greater than 2 years, are identified risk factors for progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients. While higher antibody levels have been correlated with increased viral burden as well as disease risk for other polyomaviruses, it is not known whether JCV Ab levels correlate with PML risk in natalizumab-treated patients.

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.