Plasma neurofilament light chain concentrations as a biomarker of clinical and radiologic outcomes in relapsing multiple sclerosis: Post hoc analysis of Phase 3 ozanimod trials

BACKGROUND AND PURPOSE: We investigated plasma neurofilament light chain concentration (pNfL) as a biomarker for neuroaxonal damage and disease activity using data from Phase 3 trials of ozanimod in relapsing multiple sclerosis (RMS). METHODS: pNfL was measured before and after ozanimod 0.46 mg or 0.92 mg daily or interferon β‐1a 30 µg weekly in the randomized, double‐blind SUNBEAM and RADIANCE trials. In these post hoc analyses, we investigated relationships between pNfL (at baseline and median percentage change from baseline to Month 12 [SUNBEAM] or 24 [RADIANCE]) and clinical and magnetic resonance imaging outcomes. RESULTS: Median (Q1, Q3) baseline pNfL, available in 1244 of 1346 SUNBEAM participants, was 14.70 (10.16, 23.26) pg/ml and in 1109 of 1313 RADIANCE participants was 13.35 (9.42, 20.41) pg/ml. Baseline gadolinium‐enhancing (GdE) and T2 lesion counts increased and brain volume decreased with increasing baseline pNfL. Baseline pNfL was higher in those with versus without on‐treatment relapse. Median percentage reduction in pNfL at 12 months in SUNBEAM (n = 1238) and 24 months in RADIANCE (n = 1088) was greater for ozanimod (20%–27%) than interferon β‐1a (13%–16%; p < 0.01). Greater pNfL reduction was associated with fewer GdE lesions, fewer new/enlarging T2 lesions per scan, less loss of brain volume, lower annualized relapse rate (ARR), and no evidence of disease activity. The following models predicted ARR: 0.5111 + 0.0116 × ΔNfL at 12 months (SUNBEAM) and 0.4079 + 0.0088 × ΔNfL at 24 months (RADIANCE). CONCLUSIONS: pNfL was associated with clinical and radiologic measures of disease and treatment effects in RMS, supporting its use as a biomarker.