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.

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA Center for Biomedical Imaging Clinical and Translational Science Institute University at Buffalo The State University of New York Buffalo NY USA

Buffalo Neuroimaging Analysis Center Department of Neurology Jacobs School of Medicine and Biomedical Sciences University at Buffalo The State University of New York Buffalo NY USA IRCCS Fondazione Don Carlo Gnocchi ONLUS Milan Italy

Clinical Trial Unit Department of Clinical Research University Hospital Basel University of Basel Basel Switzerland

CORe Department of Medicine The University of Melbourne Melbourne VIC Australia; Melbourne MS Centre Department of Neurology The Royal Melbourne Hospital Melbourne VIC Australia

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Katerinska 30 120 00 Prague Czech Republic

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic CORe Department of Medicine The University of Melbourne Melbourne VIC Australia

Department of Radiology 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Neurologic Clinic and Policlinic MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel University Hospital Basel University of Basel Basel Switzerland

Mult Scler. 2021 Nov;27(13):1967-1969. doi: 10.1177/13524585211049552. PubMed

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