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Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis

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Titel: Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis
Autoren: Robert J. Fox, Bruce A.C. Cree, Jérôme de Sèze, Ralf Gold, Hans-Peter Hartung, Douglas Jeffery, Ludwig Kappos, Xavier Montalban, Bianca Weinstock-Guttman, Carol M. Singh, Arman Altincatal, Nicholas Belviso, Robin L. Avila, Pei-Ran Ho, Ray Su, Robert Engle, Dipen Sangurdekar, Carl de Moor, Elizabeth Fisher, Bernd C. Kieseier, Richard A. Rudick
Weitere Verfasser: Institut Català de la Salut, [Fox RJ] Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Ohio, United States. [Cree BAC] Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, United States. [de Sèze J] Department of Neurology, Hôpital Civil, Strasbourg, France. [Gold R] Department of Neurology, St. Josef Hospital, Ruhr University, Bochum, Germany. [Hartung HP] Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. Brain and Mind Center, University of Sydney, Australia. Department of Neurology, Palacky University Olomouc, Czech Republic. [Jeffery D] Piedmont HealthCare, Mooresville, NC, United States. [Montalban X] Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus
Quelle: Neurology
Scientia
Scientia. Dipòsit d'Informació Digital del Departament de Salut
instname
Verlagsinformationen: Ovid Technologies (Wolters Kluwer Health), 2024.
Publikationsjahr: 2024
Schlagwörter: Male, Adult, Multiple Sclerosis, Time Factors, Filaments citoplasmàtics, Gadolinium, DISEASES::Nervous System Diseases::Autoimmune Diseases of the Nervous System::Demyelinating Autoimmune Diseases, CNS::Multiple Sclerosis, CHEMICALS AND DRUGS::Biological Factors::Biomarkers, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Neurofilament Proteins, Humans, Immunologic Factors, COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores, Esclerosi múltiple - Imatgeria per ressonància magnètica, Natalizumab, Otros calificadores::Otros calificadores::Otros calificadores::/diagnóstico por imagen, Other subheadings::Other subheadings::Other subheadings::/diagnostic imaging, Brain, Middle Aged, Magnetic Resonance Imaging, COMPUESTOS QUÍMICOS Y DROGAS::sustancias macromoleculares::polímeros::biopolímeros::proteínas de filamentos intermedios::proteínas de neurofilamentos, CHEMICALS AND DRUGS::Macromolecular Substances::Polymers::Biopolymers::Intermediate Filament Proteins::Neurofilament Proteins, ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple, Marcadors bioquímics, Disease Progression, Female, Biomarkers, Research Article
Beschreibung: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083).In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28.Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion.Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.
Publikationsart: Article
Other literature type
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1526-632X
0028-3878
DOI: 10.1212/wnl.0000000000209357
Zugangs-URL: https://pubmed.ncbi.nlm.nih.gov/38648580
https://hdl.handle.net/11351/11386
Rights: CC BY NC ND
URL: http://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) (http://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.
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  Data: Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis
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  Data: Institut Català de la Salut<br />[Fox RJ] Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Ohio, United States. [Cree BAC] Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, United States. [de Sèze J] Department of Neurology, Hôpital Civil, Strasbourg, France. [Gold R] Department of Neurology, St. Josef Hospital, Ruhr University, Bochum, Germany. [Hartung HP] Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. Brain and Mind Center, University of Sydney, Australia. Department of Neurology, Palacky University Olomouc, Czech Republic. [Jeffery D] Piedmont HealthCare, Mooresville, NC, United States. [Montalban X] Vall d’Hebron Hospital Universitari, Barcelona, Spain<br />Vall d'Hebron Barcelona Hospital Campus
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  Data: Serum neurofilament light chain (sNfL) levels correlate with multiple sclerosis (MS) disease activity, but the dynamics of this correlation are unknown. We evaluated the relationship between sNfL levels and radiologic MS disease activity through monthly assessments during the 24-week natalizumab treatment interruption period in RESTORE (NCT01071083).In the RESTORE trial, participants with relapsing forms of MS who had received natalizumab for ≥12 months were randomized to either continue or stop natalizumab and followed with MRI and blood draws every 4 weeks to week 28 and again at week 52 The sNfL was measured, and its dynamics were correlated with the development of gadolinium-enhancing (Gd+) lesions. Log-linear trend in sNfL levels were modeled longitudinally using generalized estimating equations with robust variance estimator from baseline to week 28.Of 175 patients enrolled in RESTORE, 166 had serum samples for analysis. Participants with Gd+ lesions were younger (37.7 vs 43.1, p = 0.001) and had lower Expanded Disability Status Scale scores at baseline (2.7 vs 3.4, p = 0.017) than participants without Gd+ lesions. sNfL levels increased in participants with Gd+ lesions (n = 65) compared with those without (n = 101, mean change from baseline to maximum sNfL value, 12.1 vs 3.2 pg/mL, respectively; p = 0.003). As the number of Gd+ lesions increased, peak median sNfL change also increased by 1.4, 3.0, 4.3, and 19.6 pg/mL in the Gd+ lesion groups of 1 (n = 12), 2-3 (n = 18), 4-9 (n = 21), and ≥10 (n = 14) lesions, respectively. However, 46 of 65 (71%) participants with Gd+ lesions did not increase above the 95th percentile threshold of the group without Gd+ lesions. The initial increase of sNfL typically trailed the first observation of Gd+ lesions, and the peak increase in sNfL was a median [interquartile range] of 8 [0, 12] weeks after the first appearance of the Gd+ lesion.Although sNfL correlated with the presence of Gd+ lesions, most participants with Gd+ lesions did not have elevations in sNfL levels. These observations have implications for the use and interpretation of sNfL as a biomarker for monitoring MS disease activity in controlled trials and clinical practice.
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  Data: CC BY NC ND<br />URL: http://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) (http://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.
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        Value: 10.1212/wnl.0000000000209357
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      – SubjectFull: Multiple Sclerosis
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      – SubjectFull: ENFERMEDADES::enfermedades del sistema nervioso::enfermedades autoinmunitarias del sistema nervioso::enfermedades autoinmunes desmielinizantes del SNC::esclerosis múltiple
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      – SubjectFull: Biomarkers
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      – SubjectFull: Research Article
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      – TitleFull: Temporal Relationship Between Serum Neurofilament Light Chain and Radiologic Disease Activity in Patients With Multiple Sclerosis
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            NameFull: Robert Engle
      – PersonEntity:
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            NameFull: Dipen Sangurdekar
      – PersonEntity:
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            NameFull: Carl de Moor
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            NameFull: Elizabeth Fisher
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            NameFull: Bernd C. Kieseier
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            NameFull: Richard A. Rudick
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            NameFull: Institut Català de la Salut
      – PersonEntity:
          Name:
            NameFull: [Fox RJ] Mellen Center for Multiple Sclerosis, Neurological Institute, Cleveland Clinic, Ohio, United States. [Cree BAC] Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, United States. [de Sèze J] Department of Neurology, Hôpital Civil, Strasbourg, France. [Gold R] Department of Neurology, St. Josef Hospital, Ruhr University, Bochum, Germany. [Hartung HP] Department of Neurology, Heinrich-Heine-University, Düsseldorf, Germany. Brain and Mind Center, University of Sydney, Australia. Department of Neurology, Palacky University Olomouc, Czech Republic. [Jeffery D] Piedmont HealthCare, Mooresville, NC, United States. [Montalban X] Vall d’Hebron Hospital Universitari, Barcelona, Spain
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            NameFull: Vall d'Hebron Barcelona Hospital Campus
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          Dates:
            – D: 14
              M: 05
              Type: published
              Y: 2024
          Identifiers:
            – Type: issn-print
              Value: 1526632X
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            – Type: volume
              Value: 102
          Titles:
            – TitleFull: Neurology
              Type: main
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