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The ability of these biomarkers to detect disease activity upon treatment discontinuation was studied.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Long-term stable relapse-onset MS patients were to continue or discontinue their first-line disease-modifying therapy(DMT) to study the safety of DMT discontinuation(DOT-MS trial NCT04260711). \u201cSignificant\u201d disease activity was defined as clinical relapse, \u22653 new lesions or \u22652 contrast-enhancing lesions. MRI and sampling were performed at baseline, month 3, 6, 12, 18 and 24. Associations of delta biomarker levels and NfL z-score(age and body mass index derived) with \u201csignificant\u201d disease activity were tested. Cut-off values for biomarkers to detect disease activity were calculated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>45(50.5%) participants discontinued their DMT. Eight(all discontinued DMT) had \u201csignificant\u201d disease activity, which was associated with an increase in NfL levels(OR:1.13 [1.03\u20131.33], <jats:italic>p<\/jats:italic>\u00a0=\u00a00.04) and NfL <jats:italic>z<\/jats:italic>-scores(OR:2.17 [0.98\u20135.22], <jats:italic>p<\/jats:italic>\u00a0=\u00a00.06), but not with GFAP(<jats:italic>p<\/jats:italic>\u00a0=\u00a00.52). Delta NfL had the highest ability to detect \u201csignificant\u201d disease activity(AUC:0.88 [0.76\u20130.99]), with the best calculated cut-off of 46.4% increase(AUC:0.68, sensitivity 0.57, specificity 0.96).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Discussion<\/jats:title>\n            <jats:p>NfL may be useful to identify, but not predict, disease activity after DMT discontinuation in MS. GFAP levels were not discriminatory for disease activity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00415-025-13231-9","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T11:06:20Z","timestamp":1753268780000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Reliability of serum neurofilament light and glial fibrillary acidic protein for detecting disease activity upon discontinuation of first-line disease-modifying therapy in stable multiple sclerosis (DOT-MS)"],"prefix":"10.1007","volume":"272","author":[{"given":"W. H.","family":"Fung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2324-0499","authenticated-orcid":false,"given":"M. H. J.","family":"Wessels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E. M. 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Fung: nothing to report; M. Wessels: nothing to report; E.M.E. Coerver: nothing to report; J. de Beukelaar received (research) grants from the Dutch National MS Foundation (OZ2019-19, OZ2021-19 and P2023-003) and Stichting BeterKeten; W.H. Bouvy: nothing to report; L. Canta received study compensation fees for Consonance study, Esteem study, Lemtrada Pass study and TOP study; O.H.H. Gerlach: nothing to report; E. Hoitsma received speaker fees from Biogen, Roche, Sanofi Genzyme; authorship fee from Sandoz and study compensation fees for Calliper study, Esteem study and Lemtrada Pass study (study payments to institution); E. Hoogervorst: nothing to report; B.A. de Jong receives research support from Dutch MS Research Foundation, National MS Foundation, Dutch Multiple Sclerosis Association, and Zorgverzekeraars Nederland (i.e. umbrella organization of health insurers in the Netherlands); N.F. Kalkers: nothing to report; Z.L.E. van Kempen: nothing to report; H. L\u00f6venich: nothing to report; C.E.P. van Munster: nothing to report; B.W. van Oosten: nothing to report; J. Smolders received speaker and\/or consultancy fees from Biogen, Merck, Novartis, Roche and Sanofi; A. Vennegoor: nothing to report; E. Zeinstra served on advisory boards\/received consultancy fees for Merck, Novartis, Genzyme and Roche; M. Barrantes-Cepas is supported by research grants from Merck and Atara Biotherapeutics; G. Kooij received grant from the Dutch Research Council (NWO Vidi grant 91719305 to G.K.), the Dutch MS Research Foundation (18-1023MS to G.K.) and research grants from Biogen, Merck and Novartis; M.M. Schoonheim serves on the editorial board of Neurology, Multiple Sclerosis Journal and Frontiers in Neurology, receives research support from the Dutch MS Research Foundation, Eurostars-EUREKA, ARSEP, Amsterdam Neuroscience, MAGNIMS and ZonMW (Vidi grant, project number 09150172010056) and has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Celgene\/Bristol Meyers Squibb, EIP, Sanofi, MedDay and Merck; B.I. Lissenberg-Witte: nothing to report; B. Moraal: nothing to report; F. Barkhof serves on the steering committee and is iDMC member for Biogen, Merck, Roche, EISAI. He acts as a consultant for Roche, Biogen, Merck, IXICO, Jansen, Combinostics. He has research agreements with Novartis, Merck, Biogen, GE, Roche. He is co-founder and share\u2013holder of Queen Square Analytics LTD; B.M.J. Uitdehaag reports consultancy fees from Immunic Therapeutics; J. Mostert: nothing to report; C.E. Teunissen reports funding from National MS Society (Progressive MS alliance) and Innovative Medicines Initiatives 3TR (Horizon 2020, grant no 831434). CET has a research contract with Celgene. She serves on editorial boards of Medidact Neurologie\/Springer, Neurology: Neuroimmunology & Neuroinflammation, and is editor of a Neuromethods book Springer; J. Killestein received research grants for multicentre investigator initiated trials DOT-MS trial, ClinicalTrials. gov Identifier: NCT04260711 (ZonMW) and BLOOMS trial (ZonMW and Treatmeds), ClinicalTrials. gov Identifier: NCT05296161); received consulting fees for F. Hoffmann-La Roche, Biogen, Teva, Merck, Novartis and Sanofi\/Genzyme (all payments to institution); reports speaker relationships with F. Hoffmann-La Roche, Biogen, Immunic, Teva, Merck, Novartis and Sanofi\/Genzyme (all payments to institution); adjudication committee of MS clinical trial of Immunic (payments to institution only); E.M.M. Strijbis serves on the editorial board of Frontiers in Neurology and receives research support from Stichting MS Research and ZonMW. Received speaker fees from Merck and Novartis.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}}],"article-number":"530"}}