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

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.

CHIT1 at Diagnosis Reflects Long‐Term Multiple Sclerosis Disease Activity

“…Both serum and CSF NfL levels have been consistently associated with long-term brain atrophy. 33,34 Of note, this effect size is similar to the percentage of variance explained for the associations between CHIT1 and disease activity measures in our work. In contrast, serum and CSF NfL levels measured at 6 to 8 years of disease duration were not associated or were at most weakly associated with future relapse activity, EDSS worsening, or lesions in 2 recent large-scale studies.…”

“…In contrast, serum and CSF NfL levels measured at 6 to 8 years of disease duration were not associated or were at most weakly associated with future relapse activity, EDSS worsening, or lesions in 2 recent large-scale studies. 33,34 Similarly, we did not detect an association between NfL levels at diagnosis and any primary outcome, and associations between CHIT1 and disease activity outcomes were importantly independent of NfL. A combination of biomarkers will likely be indicated to capture the different disease processes in MS.…”

Blood neurofilament light as a potential endpoint in Phase 2 studies in MS

“…High NfL levels in blood were also associated with higher risk of future relapses and EDSS worsening . Blood NfL levels predicted disability worsening after up to 8 years and lesion load and atrophy after 10 years in patients with MS . Notably, NfL predicted future brain and spinal cord atrophy .…”

Association of Plasma Neurofilament Light with Postoperative Delirium

“…[1][2][3] Knowledge of delirium pathophysiology is limited, but emerging evidence suggests neuronal injury may play a role. 4,5 Increasingly, fluid biomarkers of neuronal injury have been studied in a range of conditions, including traumatic brain injury (TBI), 6 multiple sclerosis, 7,8 stroke, 9 and neurodegenerative disease. 7 In delirium, prior studies examining plasma markers of neuronal injury have been mixed.…”