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Comparison of plasma and CSF Neurofilament-light in an MS trial

de Flon, P; Laurell, K; Sundström, P; Blennow, K; Söderström, L; Zetterberg, H; Gunnarsson, M; (2019) Comparison of plasma and CSF Neurofilament-light in an MS trial. Acta Neurologica Scandinavica , 139 (5) pp. 462-468. 10.1111/ane.13078. Green open access

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Abstract

OBJECTIVE: 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. MATERIALS & METHODS: 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 for two years. Thirty patients from the extension trial (STRIX-MS extension), accepting repeated lumbar punctures, were followed for an additional three 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. RESULTS: 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. CONCLUSION: 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 optimise the use in clinical trials. This article is protected by copyright. All rights reserved.

Type: Article
Title: Comparison of plasma and CSF Neurofilament-light in an MS trial
Location: Denmark
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/ane.13078
Publisher version: http://doi.org/10.1111/ane.13078
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Multiple sclerosis, cerebrospinal fluid, clinical trial, neurofilament light, plasma, rituximab, treatment
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10068849
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