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.