Serum biomarkers at disease onset for personalized therapy in multiple sclerosis

The potential for combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict worsening disability in multiple sclerosis remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across 13 European hospitals, spanned from 15 July 1994 to 18 August 2022, with follow-up until 26 September 2023. We enrolled patients with multiple sclerosis who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA) and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, the median age was 34.2 (interquartile range, 27.6-42.4) years, and 509 patients (70.2%) were female. The median follow-up duration was 6.43 (interquartile range, 4.65-9.81) years. Higher sNfL values were associated with an elevated risk of RAW [hazard ratio (HR) of 1.45; 95% confidence interval (CI) 1.19-1.76; P < 0.001], PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003) and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We also examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values exhibited a low risk of all outcomes and served as a reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in multiple sclerosis might identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

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Journal
Brain
Published
2024-08-05
DOI
https://doi.org/10.1093/brain/awae260
Citations
32
Primary Topic
Multiple Sclerosis Research Studies
Type
article
Field-Weighted Citation Impact
13.60

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article

Serum biomarkers at disease onset for personalized therapy in multiple sclerosis

María Inmaculada Domínguez‐Mozo, Ana Quiroga‐Varela, Sara Llufriú, Lucía Romero et al.
32 citations
Brain
Multiple Sclerosis Research Studies
13.60
article

Serum biomarkers at disease onset for personalized therapy in multiple sclerosis

María Inmaculada Domínguez‐Mozo, Ana Quiroga‐Varela, Sara Llufriú, Lucía Romero, Belén Pilo de la Fuente, Jaime Masjuán, Yolanda Aladro, Juan Luis Chico‐García, Francisco Pérez‐Miralles, Juan Pablo Cuello, José Rodríguez, Roberto Álvarez‐Lafuente, Xavier Montalbán, Laura Ghezzi, Lucía Ayuso, Mar Tintoré, Enric Monreal, José Ignacio Fernández-Velasco, Bonaventura Casanova, Alexander Rodero-Romero, Noelia Villarrubia, Fernando Rodríguez‐Jorge, Sergio Martínez‐Yélamos, María Luisa Martínez‐Ginés, Luís Brieva, Lucienne Costa‐Frossard, Daniela Galimberti, Lluís Ramió‐Torrentà, Luisa María Villar, Susana Sainz de la Maza, María Isabel García-Sánchez, Yolanda Blanco, Albert Saiz, Javier Zamora, Manuel Comabella, Mercedes Espiño, Sara Eichau, Lluïsa Rubio, Raquel Sainz-Amo
article en
32 citations

Abstract

The potential for combining serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) levels to predict worsening disability in multiple sclerosis remains underexplored. We aimed to investigate whether sNfL and sGFAP values identify distinct subgroups of patients according to the risk of disability worsening and their response to disease-modifying treatments (DMTs). This multicentre study, conducted across 13 European hospitals, spanned from 15 July 1994 to 18 August 2022, with follow-up until 26 September 2023. We enrolled patients with multiple sclerosis who had serum samples collected within 12 months from disease onset and before initiating DMTs. Multivariable regression models were used to estimate the risk of relapse-associated worsening (RAW), progression independent of relapse activity (PIRA) and Expanded Disability Status Scale (EDSS) score of 3. Of the 725 patients included, the median age was 34.2 (interquartile range, 27.6-42.4) years, and 509 patients (70.2%) were female. The median follow-up duration was 6.43 (interquartile range, 4.65-9.81) years. Higher sNfL values were associated with an elevated risk of RAW [hazard ratio (HR) of 1.45; 95% confidence interval (CI) 1.19-1.76; P < 0.001], PIRA (HR of 1.43; 95% CI 1.13-1.81; P = 0.003) and reaching an EDSS of 3 (HR of 1.55; 95% CI 1.29-1.85; P < 0.001). Moreover, higher sGFAP levels were linked to a higher risk of achieving an EDSS score of 3 (HR of 1.36; 95% CI 1.06-1.74; P = 0.02) and, in patients with low sNfL values, to PIRA (HR of 1.86; 95% CI 1.01-3.45; P = 0.04). We also examined the combined effect of sNfL and sGFAP levels. Patients with low sNfL and sGFAP values exhibited a low risk of all outcomes and served as a reference. Untreated patients with high sNfL levels showed a higher risk of RAW, PIRA and reaching an EDSS of 3. Injectable or oral DMTs reduced the risk of RAW in these patients but failed to mitigate the risk of PIRA and reaching an EDSS of 3. Conversely, high-efficacy DMTs counteracted the heightened risk of these outcomes, except for the risk of PIRA in patients with high sNfL and sGFAP levels. Patients with low sNfL and high sGFAP values showed an increased risk of PIRA and achieving an EDSS of 3, which remained unchanged with either high-efficacy or other DMTs. In conclusion, evaluating sNfL and sGFAP levels at disease onset in multiple sclerosis might identify distinct phenotypes associated with diverse immunological pathways of disability acquisition and therapeutic response.

BrainVol. 147(12)
Universitat Autònoma de Barcelona (ES), University of Milan (IT), Universidad de Alcalá (ES), Universitat de Girona (ES), Bellvitge University Hospital (ES), Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT), Hospital General Universitario Gregorio Marañón (ES), Institut d'Investigació Biomédica de Bellvitge (ES), Clínica Rementería (ES), Hospital Universitario Virgen Macarena (ES), Biobanco del Sistema Sanitario Público de Andalucía (ES), Spanish Multiple Sclerosis Network (ES), Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (ES), Vall d'Hebron Institut de Recerca (ES), Hospital Universitario de Getafe (ES), Hospital Universitario Príncipe de Asturias (ES), Institut d'Investigació Biomèdica de Girona (ES), Hospital Arnau de Vilanova (ES), Instituto Ramón y Cajal de Investigación Sanitaria (ES), Hospital Del Mar (ES), Municipal Institute for Medical Research (ES), Institute of Neuroimmunology of the Slovak Academy of Sciences (SK), Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (ES), Hospital Universitari de Girona Doctor Josep Trueta (ES), Hospital del Mar Research Institute (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Hospital Universitario Ramón y Cajal (ES), Instituto de Investigación Sanitaria La Fe (ES), Universitat de Barcelona (ES), University of Birmingham (GB), Universidad Europea de Madrid (ES)
Ministero della Salute, Red Española de Esclerosis Múltiple, Xarxa de Bancs de Tumors de Catalunya, Instituto de Salud Carlos III, European Regional Development Fund
Good health and well-being
Openalex Percentile: Top 1%
Multiple Sclerosis Research Studies
13.60
DOIOpen Access PDFOpenAlex
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