Fung, WH;
Wessels, MHJ;
Coerver, EME;
de Beukelaar, J;
Bouvy, WH;
Canta, LR;
Gerlach, OHH;
... Strijbis, EMM; + view all
(2025)
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).
Journal of Neurology
, 272
(8)
, Article 530. 10.1007/s00415-025-13231-9.
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Abstract
BACKGROUND: Neurofilament light(NfL) and glial fibrillary acidic protein(GFAP) are associated with disease activity in multiple sclerosis(MS), however use in monitoring remains limited. The ability of these biomarkers to detect disease activity upon treatment discontinuation was studied. METHODS: 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). “Significant” disease activity was defined as clinical relapse, ≥3 new lesions or ≥2 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 “significant” disease activity were tested. Cut-off values for biomarkers to detect disease activity were calculated. RESULTS: 45(50.5%) participants discontinued their DMT. Eight(all discontinued DMT) had “significant” disease activity, which was associated with an increase in NfL levels(OR:1.13 [1.03–1.33], p = 0.04) and NfL z-scores(OR:2.17 [0.98–5.22], p = 0.06), but not with GFAP(p = 0.52). Delta NfL had the highest ability to detect “significant” disease activity(AUC:0.88 [0.76–0.99]), with the best calculated cut-off of 46.4% increase(AUC:0.68, sensitivity 0.57, specificity 0.96). DISCUSSION: NfL may be useful to identify, but not predict, disease activity after DMT discontinuation in MS. GFAP levels were not discriminatory for disease activity.
| Type: | Article |
|---|---|
| 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) |
| Location: | Germany |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00415-025-13231-9 |
| Publisher version: | https://doi.org/10.1007/s00415-025-13231-9 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | MS, MRI in MS, Clinical trials |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10212877 |
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