Neurofilament light levels are associated with long-term outcomes in multiple sclerosis

Background: Neurofilament light chain (NfL) is a promising marker of disease activity/treatment response in multiple sclerosis (MS), although its predictive value for long-term clinical outcomes remains unclear. Objective: We measured NfL from a phase 3 trial in relapsing-remitting MS and investigated its association with outcomes after 8 and 15years. Methods: NfL concentrations were measured by single molecule array assay in cerebrospinal fluid (CSF) from MS patients (n=235) in a 2-year randomized clinical trial (RCT) of intramuscular interferon beta-1a, and in serum (n=164) from the extension study. Results: Year 2 CSF and Year 3 serum NfL were associated with brain parenchymal fraction (BPF) change over 8years (p<0.0001, r=-0.46; p<0.05. r=-0.36, respectively) and were predictive of reaching Expanded Disability Status Scale (EDSS)6.0 at Year 8 (odds ratio (OR) (upper vs lower tertile)=3.4; 95% confidence interval (CI)=1.2-9.9, p<0.05; OR=11.0, 95% CI=2.0-114.6; p<0.01, respectively). Serum NfL concentration (Year 4) was predictive of reaching EDSS score 6.0 at 15years (OR (upper vs lower tertile)=4.9; 95% CI=1.4-20.4; p<0.05). NfL concentrations were complementary to 2-year BPF change in predicting long-term outcomes. Conclusion: Serum and CSF NfL concentrations were associated with long-term clinical outcomes in MS patients and are promising biomarkers for disease severity stratification supporting treatment decisions.