Serum neurofilament light-chain levels and long-term treatment outcomes in relapsing-remitting multiple sclerosis patients: A post hoc analysis of the randomized CombiRx trial

BackgroundCombiRx was a randomized, double-blind, placebo-controlled phase 3 trial in treatment-naive relapsing-remitting multiple sclerosis (RRMS) patients randomized to intramuscular interferon beta-1a (IM IFN beta-1a), glatiramer acetate (GA), or both therapies. ObjectiveThis analysis investigated changes in serum neurofilament light-chain (sNfL) levels in response to treatment and assessed baseline sNfL as a predictor of relapse. MethodsRRMS patients treated with IM IFN beta-1a 30 mu g weekly + placebo (n = 159), GA 20 mg/mL daily + placebo (n = 172), or IM IFN beta-1a + GA (n = 344) were included. A linear mixed model compared sNfL values over time. Cox regression models analyzed baseline sNfL and gadolinium-enhancing (Gd+) lesions as predictors of relapse. ResultsIn all treatment arms, the proportion of patients with sNfL >= 16 pg/mL decreased significantly from baseline to 6 months and was maintained at 36 months. A significantly higher percentage of patients with both baseline sNfL >= 16 pg/mL and >= 1 Gd+ lesion experienced relapses within 90 days compared to patients with sNfL ConclusionsNfL levels were reduced within 6 months and remained low at 36 months. Results suggest that the combination of lesion activity and sNfL was a stronger predictor of relapse than either factor alone.