Neurofilament light levels are associated with long-term outcomes in multiple sclerosis. (November 2020)

• Record Type: Journal Article
• Authors: Kuhle, Jens; Plavina, Tatiana; Barro, Christian; Disanto, Giulio; Sangurdekar, Dipen; Singh, Carol M; de Moor, Carl; Engle, Bob; Kieseier, Bernd C; Fisher, Elizabeth; Kappos, Ludwig; Rudick, Richard A; Goyal, Jaya
• Is Part Of: Multiple sclerosis. Volume 26:Number 13(2020)
• Page Start: 1691
• Page End: 1699
• Publication Date: 2020-11
• Subjects: Neurofilament -- multiple sclerosis -- MRI; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458519885613
• Languages: English
• ISSNs: 1352-4585

Abstract

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 15 years. 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 β-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 8 years ( 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 15 years (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.