Abstract Details

Title Longitudinal stability of anti–JC virus (JCV) antibody index over 2 years in multiple sclerosis (MS) patients treated with natalizumab in the ASCEND study

Topic Multiple Sclerosis

Presentation(s) P4 - Poster Session 4 (5:30 PM-6:30 PM)

Poster/Presentation
Number 15-009

Objective To evaluate longitudinal anti-JCV antibody index (“index”) changes in patients treated with natalizumab or placebo over 2 years in the ASCEND study.

Background Anti-JCV antibodies are a risk factor for progressive multifocal leukoencephalopathy (PML) in natalizumab-treated patients. In anti-JCV antibody positive patients without prior immunosuppressant use, index level correlates with PML risk and allows improved risk stratification. No randomized, placebo-controlled data on longitudinal index change have previously been assessed.

Design/Methods ASCEND was a randomized, double-blind, placebo-controlled phase 3 trial conducted in patients with secondary progressive MS. Samples for anti-JCV antibody analyses were collected every 24 weeks. Investigators were blinded to results until study completion. Patients with index values at baseline, 48 weeks, and 96 weeks were included.

Results In ASCEND, 889 patients were randomized (placebo, 449; natalizumab, 440); 662 had index data at all 3 time points (placebo, 320; natalizumab, 342). The mean change in index from baseline to 96 weeks was small (placebo, −0.122; natalizumab, −0.198). When stratified by baseline index value, mean index values appeared to be stable over time, with no differences between the natalizumab and placebo groups. Proportions of patients in each index group between baseline and 96 weeks were similar in the 2 treatment groups (index ≤0.4: natalizumab, 41.8%−43.9%; placebo, 44.4%−45.0%; index >0.4 to ≤0.9: natalizumab, 12.9%−16.1%; placebo, 12.5%−13.8%; index >0.9 to ≤1.5: natalizumab, 9.9%−11.1%; placebo, 7.2%−10.3%; index >1.5: natalizumab, 30.1%−34.8%; placebo, 31.3%−35.3%). At 108 weeks, the Kaplan-Meier–estimated cumulative probability of changing from index ≤0.9 to >1.5 without reversion to index ≤1.5 was 4.1% with natalizumab and 3.1% with placebo.

Conclusions

This analysis in a placebo-controlled trial population provides robust evidence that natalizumab treatment is not associated with changes in index over 2 years. The stability of index regardless of natalizumab treatment supports the use of index for individualized patient management.

Authors/Disclosures
Louise Mason PRESENTER	No disclosure on file
Thomas A. Berger, MD (Dept. of Neurology, Medical University of Vienna)	Prof. Berger has received personal compensation in the range of $10,000-$49,999 for serving as a speaker at scientific meetings and participant of local and international advisory boards with various companies producing and markerting treatments for multiple sclerosis (Almirall, Biogen, Biologix, Bionorica, Celgene-BMS, Merck, Novartis, Roche, Sanofi-Genzyme, TG Therapeutics, UCB).
Raju Kapoor, MD	No disclosure on file
Hans-Peter Hartung, MD, FAAN (Heinrich Heine University Medical Faculty)	Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS Celgene. Dr. Hartung has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Geneuro. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Merck. Dr. Hartung has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bayer. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for TG Therapeutics. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Dr. Hartung has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers Neurology.
Ih Chang	Ih Chang has received personal compensation for serving as an employee of Cerevel. Ih Chang has received stock or an ownership interest from Cerevel Therapeutics.
Zheng Ren	Zheng Ren has received personal compensation for serving as an employee of Biogen.
Nolan Campbell	Nolan Campbell has received personal compensation for serving as an employee of Biogen. Nolan Campbell has stock in Biogen.
Pei-Ran Ho	No disclosure on file

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