Plasma neurofilament analysis in VITALITY-ALS.

Objective: To evaluate correlations between neurofilament (Nf) concentrations and clinical characteristics and disease progression using a large longitudinal dataset from VITALITY-ALS (ClinicalTrials.gov identifier: NCT02496767), a 48-week, randomized, double-blind, placebo-controlled clinical trial of tirasemtiv in people with ALS (pALS).
Methods: Plasma was collected at baseline and every 8 weeks thereafter. Results were compared between treatment groups and evaluated by clinical characteristics and over time. Pearson's correlation coefficients ( r ) were calculated to evaluate associations between Nf concentrations and slow vital capacity (SVC), Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score, and pre-study/in-study rates of disease progression (psRDP/isRDP).
Results: Nf measurements were available from 101 placebo- and 161 tirasemtiv -treated people with ALS (pALS). There were no significant differences in Nf between placebo and tirasemtiv groups at any time point; further analyses grouped all samples. At baseline, Nf concentration did not differ by multiple clinical characteristics. Baseline Nf light chain (NfL) concentration correlated with the psRDP ( r  = 0.50, p  < 0.001) and isRDP ( r  = 0.53, p  < 0.0001). Phosphorylated Nf heavy chain (pNfH) demonstrated a similar, but less robust, pattern of results. Baseline Nf concentration correlated with change in SVC and ALSFRS-R score over time. Plasma pNfH concentration continuously decreased over time. There was no meaningful change in plasma NfL concentration over the study period.
Conclusions: In this large longitudinal study, baseline NfL concentration correlated with multiple markers of disease progression. The findings suggest Nfs show promise primarily as prognostic markers for pALS, particularly for those with rapid disease progression.