Measurement of neurofilaments improves stratification of future disease activity in early multiple sclerosis

Abstract

Background: The added value of neurofilament light chain levels in serum (sNfL) to the concept of no evidence of disease activity-3 (NEDA-3) has not yet been investigated in detail. Objective: To assess whether combination of sNfL with NEDA-3 status improves identification of patients at higher risk of disease activity during the following year. Methods: We analyzed 369 blood samples from 155 early relapsing-remitting MS patients on interferon beta-1a. We compared disease activity, including the rate of brain volume loss in subgroups defined by NEDA-3 status and high or low sNfL (> 90th or < 90th percentile). Results: In patients with disease activity (EDA-3), those with higher sNFL had higher odds of EDA-3 in the following year than those with low sNFL (86.5% vs 57.9%; OR = 4.25, 95% CI: [2.02, 8.95]; p = 0.0001) and greater whole brain volume loss during the following year (β = −0.36%; 95% CI = [−0.60, −0.13]; p = 0.002). Accordingly, NEDA-3 patients with high sNfL showed numerically higher disease activity (EDA-3) in the following year compared with those with low sNfL (57.1% vs 31.1%). Conclusion: sNfL improves the ability to identify patients at higher risk of future disease activity, beyond their NEDA-3 status. Measurement of sNfL may assist clinicians in decision-making by providing more sensitive prognostic information.

Contributors to SerumNfLLevels in People without Neurologic Disease

“…For example, people with amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD) have an estimated 10‐fold increase in CSF NfL levels relative to healthy controls 2 ; CSF NfL levels in these individuals are also strongly correlated with serum levels, and both are associated with worse functional status 4,5 . Similarly, in multiple sclerosis (MS), serum NfL (sNfL) levels are associated with clinico‐radiological measures of disease activity, are modulated by MS disease modifying therapies, and predict disability worsening and brain atrophy 6–10 . Thus, combined with its strong relevance to underlying pathological disease processes and the relative ease with which serum samples can be obtained, sNfL is emerging as a potential disease prognostic and monitoring tool in clinical care for several neurological disorders.…”

“…4,5 Similarly, in multiple sclerosis (MS), serum NfL (sNfL) levels are associated with clinico-radiological measures of disease activity, are modulated by MS disease modifying therapies, and predict disability worsening and brain atrophy. [6][7][8][9][10] Thus, combined with its strong relevance to underlying pathological disease processes and the relative ease with which serum samples can be obtained, sNfL is emerging as a potential disease prognostic and monitoring tool in clinical care for several neurological disorders.…”

Prognostic Value of Serum Neurofilament Light Chain for Disease Activity and Worsening in Patients With Relapsing Multiple Sclerosis: Results From the Phase 3 ASCLEPIOS I and II Trials

“…NfL has been proposed as a prognostic and monitoring biomarker in MS to assess disease activity; the cumulative evidence for NfL has been reviewed elsewhere ( 25 ). In patients with RMS, high sNfL levels were found to correlate with active T2 lesions and relapses ( 3 , 16 , 20 ) and brain volume loss ( 26 ), suggesting that measuring sNfL levels can add value as a prognostic biomarker to identify patients at higher risk for future disease activity that can assist clinicians in decision-making ( 3 , 18 , 24 , 27 , 28 ).…”

The prognostic significance of early blood neurofilament light chain concentration and magnetic resonance imaging variables in relapse‐onset multiple sclerosis

“…Our finding of a trend toward a greater rate of increase in bNfL, independent of T2LV, in the poor prognostic group is supported by other recent studies. In a large mixed cohort of pwMS, and in a separate RRMS group, NfL appeared to provide additional prognostic information regarding future inflammatory disease activity, in addition to that determined through the monitoring of clinical and MRI variables (new T2 lesions or enhancing lesions) (Benkert et al, 2022, Uher et al, 2021.…”

“…Our finding of a trend toward a greater rate of increase in bNfL, independent of T2LV, in the poor prognostic group is supported by other recent studies. In a large mixed cohort of pwMS, and in a separate RRMS group, NfL appeared to provide additional prognostic information regarding future inflammatory disease activity, in addition to that determined through the monitoring of clinical and MRI variables (new T2 lesions or enhancing lesions) (Benkert et al., 2022 , Uher et al., 2021 ). While one should be cautious about applying such group‐level data to individual patients, these results suggest that incorporating NfL monitoring into clinical practice may be useful in improving our ability to predict future disease activity.…”