Association of Serum Neurofilament Light Levels with Long-term Brain Atrophy in Patients with a First Multiple Sclerosis Episode

Abstract

Importance: Data are needed on the potential long-term prognostic association of serum neurofilament light in multiple sclerosis (MS). Objective: To evaluate serum neurofilament light as a biomarker associated with long-term disease outcomes in clinically isolated syndrome. Design, Setting, and Participants: This post hoc cohort study used data from the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study, a 36-month, multicenter, placebo-controlled interferon β-1a randomized clinical trial conducted from April 1996 to March 2000, and its long-term (5- and 10-year) extension study from February 2001 to March 2009. Participants included individuals with a symptomatic initial demyelinating event and brain magnetic resonance imaging (MRI) lesions suggestive of MS. Data were analyzed from April 2017 through 2019. Exposure: The variable of interest was naturally occurring serum neurofilament light concentration Main Outcomes and Measures: Gadolinium-enhancing (Gd+) lesion number, T2 lesion volume, and brain parenchymal fraction, a measure of brain atrophy were measured at baseline and 5 and 10 years. Multivariate regression models evaluated whether age, sex, and baseline covariates, including serum neurofilament light, brain parenchymal fraction, Expanded Disability Status Scale, Gd+lesion count, and T2 lesion volume, were associated with brain parenchymal fraction changes over 5 and 10 years. Results: Among 308 included participants (mean [SD] age, 33.2 [7.6] years; 234 [76.0%] women), baseline serum neurofilament light concentrations were associated with Gd+lesions (Spearman r = 0.41; P