Longitudinal course of neurofilament light chain levels in amyotrophic lateral sclerosis : insights from a completed randomized controlled trial with rasagiline

Abstract

Background and purpose: Rasagiline might be disease modifying in patients with amyo-trophic lateral sclerosis (ALS). The aim was to evaluate the effect of rasagiline 2 mg/day on neurofilament light chain (NfL), a prognostic biomarker in ALS.Methods: In 65 patients with ALS randomized in a 3:1 ratio to rasagiline 2 mg/day (n= 48) or placebo (n= 17) in a completed randomized controlled multicentre trial, NfL levels in plasma were measured at baseline, month 6 and month 12. Longitudinal changes in NfL levels were evaluated regarding treatment and clinical parameters.Results: Baseline NfL levels did not differ between the study arms and correlated with disease progression rates both pre-baseline (r= 0.64, p< 0.001) and during the study (r=0.61, p< 0.001). NfL measured at months 6 and 12 did not change significantly from base-line in both arms, with a median individual NfL change of +1.4 pg/mL (interquartile range [IQR] −5.6, 14.2) across all follow-up time points. However, a significant difference in NfL change at month 12 was observed between patients with high and low NfL baseline levels treated with rasagiline (high [n= 13], −6.9 pg/mL, IQR −20.4, 6.0; low [n= 18], +5.9 pg/mL, IQR −1.4, 19.7; p= 0.025). Additionally, generally higher longitudinal NfL variability was observed in patients with high baseline levels, whereas disease progression rates and disease duration at baseline had no impact on the longitudinal NfL course.Conclusion: Post hoc NfL measurements in completed clinical trials are helpful in inter-preting NfL data from ongoing and future interventional trials and could provide hypoth-esis-generating complementary insights. Further studies are warranted to ultimately differentiate NfL response to treatment from other factors.