{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:11:40Z","timestamp":1792141900829,"version":"4.4.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Swiss National Science Foundation","doi-asserted-by":"publisher","award":["320030_189140"],"award-info":[{"award-number":["320030_189140"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017147","name":"Progressive MS Alliance","doi-asserted-by":"publisher","award":["PA-2007-36872"],"award-info":[{"award-number":["PA-2007-36872"]}],"id":[{"id":"10.13039\/100017147","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008486","name":"Swiss MS Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008486","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In multiple sclerosis (MS) patients under therapy, the increase of serum glial fibrillary acidic protein (sGFAP) concentrations is associated with the course of \u2018progression in absence of relapse\u2019 (PIRA). While serum neurofilament light chain (sNfL) reflects both response as well as insufficient or lack of efficiency of disease-modifying therapies (DMT), the longitudinal course of sGFAP levels as a drug response marker for future PIRA in relation to specific types of DMT is less clear.<\/jats:p>\n                  <jats:p>We aimed to compare the predictive capacity of sGFAP and sNfL for PIRA and relapse activity and the longitudinal course in people with MS (PwMS) treated with fingolimod, based on Z scores derived from normative values. Overall, 420 PwMS under fingolimod treatment with follow-up of 9.1 years (interquartile range: 7.0\u201311.0) from the Swiss MS Cohort, contributing 2935 longitudinal serum samples, were included. A reference data set for sGFAP established from 4297 healthy controls across three European and North American cohorts was used to calculate Z scores. The longitudinal course and the predictive capacity of biomarkers for time to PIRA and relapse were assessed by Cox proportional hazards and linear mixed-effects models.<\/jats:p>\n                  <jats:p>In controls, sGFAP concentrations were 13.6% higher in females than males and increased exponentially with age. Altogether, 31.0% of PwMS experienced \u22651 PIRA event. Elevated sGFAP Z scores (&amp;gt;0.75) were associated with increased risk of PIRA [hazard ratio (HR): 1.64; 95% confidence interval (CI): 1.16\u20132.32; P = 0.006], while this was not the case for sNfL. Conversely, elevated sNfL predicted relapses (HR: 1.58; 95% CI: 1.13\u20132.23; P = 0.008), while sGFAP did not. Both biomarkers decreased under treatment: sGFAP by 0.19 Z score units (ZSU)\/10 years (95% CI: \u22120.27 to \u22120.11; P &amp;lt; 0.001) and sNfL by 0.16 ZSU\/10 years (95% CI: \u22120.27 to \u22120.06; P = 0.002). Serum GFAP remained elevated in PwMS with future PIRA events (estimate: 0.29; 95% CI: 0.07\u20130.50; P = 0.009); no such association was found for sNfL. Serum GFAP and sNfL Z scores provide complementary predictive capacity for PIRA and relapse risk. The decrease of sGFAP under fingolimod is a feature not observed with other types of DMT and may hint to a specific anti-neurodegenerative effect of Sphingosine-1-phosphate-receptor modulators on astrocytes.<\/jats:p>","DOI":"10.1093\/brain\/awaf433","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T13:04:06Z","timestamp":1763039046000},"page":"2295-2307","source":"Crossref","is-referenced-by-count":28,"title":["GFAP and NfL as predictors of disease progression and relapse activity in fingolimod-treated multiple sclerosis"],"prefix":"10.1093","volume":"149","author":[{"given":"Aleksandra","family":"Maleska Maceski","sequence":"first","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Benkert","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]},{"name":"Department of Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"Einsiedler","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Schaedelin","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]},{"name":"Department of Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5359-7961","authenticated-orcid":false,"given":"Johanna","family":"Oechtering","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 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University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]},{"name":"Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]},{"name":"Dipartimento di Scienze della Salute, Universit\u00e0 Degli Studi di Genova , Genova 16132 ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3092-8737","authenticated-orcid":false,"given":"Riccardo","family":"Galbusera","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]},{"name":"Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical Engineering, Faculty of Medicine, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edoardo","family":"Galli","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1394-8231","authenticated-orcid":false,"given":"Jannis","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Centre and Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Neurology, Departments of Biomedicine and Clinical Research, University Hospital and University Basel , Basel 4031 ,","place":["Switzerland"]},{"name":"Translational Imaging in Neurology (ThINK) Basel, Department of Biomedical 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University of Bern , Bern 3010 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Inselspital, Bern University Hospital, University of Bern , Bern 3010 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Disanto","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale , Lugano 6900 ,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Zecca","sequence":"additional","affiliation":[{"name":"Multiple Sclerosis Center, Neurocenter of Southern Switzerland, Ente Ospedaliero Cantonale , Lugano 6900 ,","place":["Switzerland"]},{"name":"Faculty of Biomedical Sciences, Universit\u00e0 Della Svizzera Italiana (USI) , Lugano 6900 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