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Blood neurofilament light chain as a biomarker of MS disease activity and treatment response

OBJECTIVE: To assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis. METHODS: We measured NfL in blood samples from 589 patient...

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Autores principales: Kuhle, Jens, Kropshofer, Harald, Haering, Dieter A., Kundu, Uma, Meinert, Rolf, Barro, Christian, Dahlke, Frank, Tomic, Davorka, Leppert, David, Kappos, Ludwig
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442011/
https://www.ncbi.nlm.nih.gov/pubmed/30737333
http://dx.doi.org/10.1212/WNL.0000000000007032
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author Kuhle, Jens
Kropshofer, Harald
Haering, Dieter A.
Kundu, Uma
Meinert, Rolf
Barro, Christian
Dahlke, Frank
Tomic, Davorka
Leppert, David
Kappos, Ludwig
author_facet Kuhle, Jens
Kropshofer, Harald
Haering, Dieter A.
Kundu, Uma
Meinert, Rolf
Barro, Christian
Dahlke, Frank
Tomic, Davorka
Leppert, David
Kappos, Ludwig
author_sort Kuhle, Jens
collection PubMed
description OBJECTIVE: To assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis. METHODS: We measured NfL in blood samples from 589 patients with relapsing-remitting multiple sclerosis (from phase 3 studies of fingolimod vs placebo, FREEDOMS and interferon [IFN]-β-1a, TRANSFORMS) and 35 healthy controls and compared NfL levels with clinical and MRI-related outcomes. RESULTS: At baseline, NfL levels (pg/mL) were higher in patients than in healthy controls (30.5 and 27.0 vs 16.9, p = 0.0001) and correlated with T2 lesion load and number of gadolinium-enhancing T1 lesions (p < 0.0001, both). Baseline NfL levels, treatment, and number of new or enlarging T2 lesions during the studies predicted NfL levels at the end of study (all p < 0.01). High vs low baseline NfL levels were associated (estimate [95% confidence interval]) with an increased number of new or enlarging T2 lesions (ratio of mean: 2.64 [1.51–4.60]; p = 0.0006), relapses (rate ratio: 2.53 [1.67–3.83]; p < 0.0001), brain volume loss (difference in means: −0.78% [−1.02 to −0.54]; p < 0.0001), and risk of confirmed disability worsening (hazard ratio: 1.94 [0.97–3.87]; p = 0.0605). Fingolimod significantly reduced NfL levels already at 6 months (vs placebo 0.73 [0.656–0.813] and IFN 0.789 [0.704–0.884]), which was sustained until the end of the studies (vs placebo 0.628 [0.552–0.714] and IFN 0.794 [0.705–0.894]; p < 0.001, both studies at all assessments). CONCLUSIONS: Blood NfL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value. Our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response.
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spelling pubmed-64420112019-04-15 Blood neurofilament light chain as a biomarker of MS disease activity and treatment response Kuhle, Jens Kropshofer, Harald Haering, Dieter A. Kundu, Uma Meinert, Rolf Barro, Christian Dahlke, Frank Tomic, Davorka Leppert, David Kappos, Ludwig Neurology Article OBJECTIVE: To assess the value of blood neurofilament light chain (NfL) as a biomarker of recent, ongoing, and future disease activity and tissue damage and its utility to monitor treatment response in relapsing-remitting multiple sclerosis. METHODS: We measured NfL in blood samples from 589 patients with relapsing-remitting multiple sclerosis (from phase 3 studies of fingolimod vs placebo, FREEDOMS and interferon [IFN]-β-1a, TRANSFORMS) and 35 healthy controls and compared NfL levels with clinical and MRI-related outcomes. RESULTS: At baseline, NfL levels (pg/mL) were higher in patients than in healthy controls (30.5 and 27.0 vs 16.9, p = 0.0001) and correlated with T2 lesion load and number of gadolinium-enhancing T1 lesions (p < 0.0001, both). Baseline NfL levels, treatment, and number of new or enlarging T2 lesions during the studies predicted NfL levels at the end of study (all p < 0.01). High vs low baseline NfL levels were associated (estimate [95% confidence interval]) with an increased number of new or enlarging T2 lesions (ratio of mean: 2.64 [1.51–4.60]; p = 0.0006), relapses (rate ratio: 2.53 [1.67–3.83]; p < 0.0001), brain volume loss (difference in means: −0.78% [−1.02 to −0.54]; p < 0.0001), and risk of confirmed disability worsening (hazard ratio: 1.94 [0.97–3.87]; p = 0.0605). Fingolimod significantly reduced NfL levels already at 6 months (vs placebo 0.73 [0.656–0.813] and IFN 0.789 [0.704–0.884]), which was sustained until the end of the studies (vs placebo 0.628 [0.552–0.714] and IFN 0.794 [0.705–0.894]; p < 0.001, both studies at all assessments). CONCLUSIONS: Blood NfL levels are associated with clinical and MRI-related measures of disease activity and neuroaxonal damage and have prognostic value. Our results support the utility of blood NfL as an easily accessible biomarker of disease evolution and treatment response. Lippincott Williams & Wilkins 2019-03-05 /pmc/articles/PMC6442011/ /pubmed/30737333 http://dx.doi.org/10.1212/WNL.0000000000007032 Text en Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
spellingShingle Article
Kuhle, Jens
Kropshofer, Harald
Haering, Dieter A.
Kundu, Uma
Meinert, Rolf
Barro, Christian
Dahlke, Frank
Tomic, Davorka
Leppert, David
Kappos, Ludwig
Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
title Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
title_full Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
title_fullStr Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
title_full_unstemmed Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
title_short Blood neurofilament light chain as a biomarker of MS disease activity and treatment response
title_sort blood neurofilament light chain as a biomarker of ms disease activity and treatment response
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442011/
https://www.ncbi.nlm.nih.gov/pubmed/30737333
http://dx.doi.org/10.1212/WNL.0000000000007032
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