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.

ABSTRACT

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 ß-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 ß-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.