Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis.

MULTIPLE SCLEROSIS

Journal

Journal of neurology, neurosurgery, and psychiatry
ISSN: 1468-330X
Titre abrégé: J Neurol Neurosurg Psychiatry
Pays: England
ID NLM: 2985191R

Informations de publication

Date de publication:
08 Nov 2023
Historique:
received: 18 07 2023
accepted: 21 10 2023
medline: 9 11 2023
pubmed: 9 11 2023
entrez: 8 11 2023
Statut: aheadofprint

Résumé

We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS). A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods. Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change. Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.

Sections du résumé

BACKGROUND BACKGROUND
We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS).
METHODS METHODS
A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods.
RESULTS RESULTS
Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change.
CONCLUSIONS CONCLUSIONS
Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.

Identifiants

pubmed: 37940409
pii: jnnp-2023-332251
doi: 10.1136/jnnp-2023-332251
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Nicolás Fissolo (N)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain.

Pascal Benkert (P)

Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.

Jaume Sastre-Garriga (J)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain.

Neus Mongay-Ochoa (N)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain.

Andreu Vilaseca-Jolonch (A)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain.

Sara Llufriu (S)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Yolanda Blanco (Y)

Center of Neuroimmunology, Service of Neurology, Hospital Clinic and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.

Harald Hegen (H)

Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.

Klaus Berek (K)

Department of Neurology, Innsbruck Medical University, Innsbruck, Austria.

Francisco Perez-Miralles (F)

Neuroimmunology Unit, València University and Polytechnic Hospital La Fe, Valencia, Spain.

Konrad Rejdak (K)

Department of Neurology, Medical University of Lublin, Lublin, Poland.

Luisa M Villar (LM)

Departments of Neurology and Immunology, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal deInvestigacion Sanitaria (IRYCIS), Madrid, Spain.

Enric Monreal (E)

Department of Neurology, Hospital Universitario Ramón y Cajal, REEM, IRYCIS, Universidad de Alcalá, Madrid, Spain.

Roberto Alvarez-Lafuente (R)

Environmental Factors in Degenerative Diseases Research Group, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico SanCarlos (IdISSC), Madrid, Spain.

Onder K Soylu (OK)

Department of Neurology, Ulm University, Ulm, Germany.

Ahmed Abdelhak (A)

Department of Neurology, Ulm University, Ulm, Germany.
Department of Neurology, Division of Neuroinflammation and Glial Biology, University of California San Francisco, San Francisco, California, USA.

Franziska Bachhuber (F)

Department of Neurology, Ulm University, Ulm, Germany.

Hayrettin Tumani (H)

Department of Neurology, Ulm University, Ulm, Germany.

Sergio Martínez-Yélamos (S)

Neurology Department, Multiple Sclerosis Unit, Hospital Universitari deBellvitge-IDIBELL, Universitat de Barcelona, Barcelona, Spain.

Antonio J Sánchez-López (AJ)

Neuroimmunology Unit, Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain.
Biobank, Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain.

Antonio García-Merino (A)

Neuroimmunology Unit, Puerta de Hierro-Segovia de Arana Health Research Institute, Madrid, Spain.

Lucía Gutiérrez (L)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain.

Tamara Castillo-Trivino (T)

Neurology Department, Donostia University Hospital, San Sebastian, Spain.

Jan Lycke (J)

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Igal Rosenstein (I)

Department of Clinical Neuroscience, Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Roberto Furlan (R)

Clinical Neuroimmunology Unit, Division of Neuroscience, Institute of Experimental Neurology, IRCCS Ospedale San Raffaele, Milan, Italy.

Massimo Filippi (M)

Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy.
Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy.
Università Vita Salute San Raffaele, Milano, Italy.

Nieves Téllez (N)

Neurology Department, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.

Lluís Ramió-Torrentà (L)

Girona Neuroimmunology and Multiple Sclerosis Unit, Neurology Department,Hospital Universitari Dr. Josep Trueta and Hospital Santa Caterina.Neurodegeneration and Neuroinflammation research group (IDIBGI). Department of Medical Sciences, University of Girona, Girona, Spain.

Jan D Lünemann (JD)

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Munster, Germany.

Heinz Wiendl (H)

Department of Neurology with Institute of Translational Neurology, University Hospital Münster, Munster, Germany.

Sara Eichau (S)

Multiple Sclerosis Unit, Neurology Service, Hospital Universitario Virgen Macarena, Sevilla, Spain.

Michael Khalil (M)

Department of Neurology, Medical University of Graz, Graz, Austria.

Jens Kuhle (J)

Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Departments of Biomedicine and Clinical Research, University Hospital and University of Basel, Basel, Switzerland.
Department of Neurology, University Hospital and University of Basel, Basel, Switzerland.

Xavier Montalban (X)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain.

Manuel Comabella (M)

Servei de Neurologia-Neuroimmunologia, Centre d'Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d'Hebron (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Vall d'Hebron University Hospital, Barcelona, Spain manuel.comabella@vhir.org.

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