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Comparison of plasma and cerebrospinal fluid neurofilament light in a multiple sclerosis trial.

Journal article
Authors Pierre de Flon
Katarina Laurell
Peter Sundström
Kaj Blennow
Lars Söderström
Henrik Zetterberg
Published in Acta neurologica Scandinavica
Volume 139
Issue 5
Pages 462-468
ISSN 1600-0404
Publication year 2019
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 462-468
Language en
Keywords Adult, Biomarkers, analysis, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunologic Factors, therapeutic use, Male, Middle Aged, Multiple Sclerosis, Relapsing-Remitting, drug therapy, metabolism, Neurofilament Proteins, analysis, metabolism, Rituximab, therapeutic use
Subject categories Neurochemistry


The main objective of this study was to evaluate the axonal component neurofilament light protein (NFL) in plasma and cerebrospinal fluid (CSF) as an outcome measure in a clinical trial on disease-modifying treatments in multiple sclerosis.Seventy-five patients with clinically stable relapsing-remitting multiple sclerosis (RRMS) participating in the clinical trial "Switch-To RItuXimab in MS" (STRIX-MS) were switched to rituximab from first-line injectable therapy and then followed up for 2 years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed up for an additional 3 years. Plasma and CSF samples were collected yearly during the follow-up. NFL concentration in plasma was measured by an in-house NF-light assay on the Simoa platform with a Homebrew kit. NFL concentration in CSF was measured by sandwich ELISA.The mean levels of NFL, in both CSF and plasma, were low. The reduction of CSF-NFL was 25% during the first year of follow-up (from a mean of 471 [SD 393] to 354 [SD 174] pg/mL; P = 0.006) and was statistically significant. The corresponding reduction in plasma NFL was 18% (from 9.73 [SD 7.04] to 7.94 [SD 3.10] pg/mL; P = 0.055) and did not reach statistical significance.This study indicates that NFL in plasma is less sensitive as an endpoint in group comparisons than NFL in CSF. Given that plasma NFL is far easier to access, it is a promising and awaited method but further studies are needed to optimize the use in clinical trials.

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