What question did this study set out to answer?

This research aims to determine if neurofilament light chain can effectively reflect disease activity and treatment response in multiple sclerosis.

January 25, 2026

Neurofilament light chain as a surrogate candidate for disease activity in multiple sclerosis (LUMINOUS)—A meta-regression of randomized controlled trials

Key Points

This research aims to determine if neurofilament light chain can effectively reflect disease activity and treatment response in multiple sclerosis.
Conducted systematic PubMed search for RCTs in multiple sclerosis from 1999 to 2023.
Included RCTs had a duration of 24 months or more and data on serum/plasma NfL.
Evaluated treatment effects on s/pNfL, annualized relapse rate, confirmed disability worsening, MRI lesions, and brain volume change.
Fifteen RCTs with 6814 participants were analyzed, including 5221 in relapsing MS and 1593 in progressive MS.
Moderate associations were observed between treatment effects on s/pNfL and MRI lesions (R² = 0.42) and annualized relapse rate (R² = 0.33).
The strongest associations in relapsing MS trials were noted for annualized relapse rate (R² = 0.45) and confirmed disability worsening (R² = 0.50).

Abstract

Background/Objectives: Neurofilament light chain (NfL) is a promising biomarker for monitoring disease activity and treatment response in multiple sclerosis (MS). This meta-regression assesses the relationship between treatment effects on serum/plasma NfL (s/pNfL) and clinical and radiological endpoints in randomized controlled trials (RCTs). Methods: A systematic PubMed search identified RCTs in MS (1999–2023) with ⩾24 months’ duration and s/pNfL data. Extracted outcomes included treatment effects on s/pNfL, annualized relapse rate (ARR), confirmed disability worsening (CDW), magnetic resonance imaging (MRI) new/enlarging T2 lesions, and percentage brain volume change (PBVC). We evaluated the association of treatment effect on the selected outcomes at the trial level by a meta-regression, weighted by trial size and duration. Results: Fifteen RCTs ( n = 6814) were included, nine in relapsing MS (RMS, n = 5221), and six in progressive MS (PMS, n = 1593). Treatment effects on s/pNfL showed a moderate association with treatment effects on MRI new/enlarging T2 lesions ( R 2 = 0.42, p = 0.01), ARR ( R 2 = 0.33, p = 0.03) and CDW ( R 2 = 0.30, p = 0.04), but not with PBVC. In RMS-only trials, association with ARR ( R 2 = 0.45, p = 0.05) and CDW ( R 2 = 0.50, p = 0.03) was more pronounced. Conclusion: In MS, treatment effects on s/pNfL are moderately associated with therapeutic effects on ARR, MRI new/enlarging T2 lesions, and CDW, whereas no consistent association was observed with PBVC.

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