067 Neurofilament light chain concentration predicts risk of relapse in participants with relapsing multiple sclerosis in phase 3 ozanimod trials. (23rd August 2021)

• Record Type: Journal Article
• Authors: Harris, Sarah; Comi, Giancarlo; Cree, Bruce AC; Steinman, Lawrence; Sheffield, James K; Southworth, Harry; Kappos, Ludwig; Cohen, Jeffrey A
• Is Part Of: BMJ neurology open. Volume 3(2021) Supplement 1
• Page Start: A24
• Page End: A25
• Publication Date: 2021-08-23
• Subjects: Neurology -- Periodicals; 616.8
• DOI: 10.1136/bmjno-2021-ANZAN.67
• Languages: English
• ISSNs: 2632-6140

Abstract

Abstract : Objectives: Plasma neurofilament light chain concentration (pNfL-c) is increased in patients with multiple sclerosis (MS) and may serve as a biomarker for neurologic damage and disease activity in relapsing MS. We analyzed changes in pNfL-c and on-treatment risk of relapse with ozanimod vs interferon β-1a (IFN). Methods: In this post hoc analysis of the phase 3 SUNBEAM (NCT02294058 ; ≥12 months) and RADIANCE (NCT02047734 ; 24 months) trials, pNfL-c was measured at baseline and after 12 and 24 months of treatment with oral ozanimod 0.46 or 0.92 mg/d or intramuscular IFN 30 µg/wk. Poisson generalized linear models were used to fit the number of relapses as a function of baseline pNfL-c and treatment group with an offset for duration. Predictive modeling of expected annualized relapse rate (ARR) was calculated using median percentage change in pNfL-c from baseline. Results: At end of treatment, median pNfL-c was reduced from baseline by 20%–23% ( P< 0.01) and 23%–27% ( P≤ 0.0001) with ozanimod 0.46 and 0.92 mg, respectively, and by 13%–15% with IFN. Higher baseline pNfL-c was associated with more relapses ( P <0.0001), and greater median reductions in pNfL-c from baseline were associated with lower ARR. Predictive modeling estimated that a 25% reduction in pNfL-c, similar to that observed with ozanimod 0.92 mg, predicts an ARR (standard error [SE]) of 0.18–0.23 (0.4), whereas a 13% reduction, similar to IFN, predicts an ARR (SE) of 0.29–0.37 (0.04). Conclusion: Our findings support pNfL-c as a biomarker for relapsing MS disease activity. Ozanimod caused greater dose-dependent reductions in pNfL-c and ARR than IFN.