Evidence map›Paper›PMID 40699373›Full record

Trial reportJournal of neurology2025

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).

W H Fung, M H J Wessels, E M E Coerver, J de Beukelaar, W H Bouvy, L R Canta, O H H Gerlach, E Hoitsma, E L J Hoogervorst, B A de Jong and 19 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04260711 (The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04260711 naunknown statusnot on this map

The Safety and Cost-effectiveness of Discontinuing Disease-modifying Therapies in Stable Relapsing - Onset Multiple Sclerosis (DOT-MS): a Randomized Rater-blinded Multicenter Trial.

TypeinterventionalSponsorAmsterdam UMC, location VUmcRan2020 to 2024Enrolled130ConditionsMultiple Sclerosis, Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis, Secondary ProgressiveArmsDMT
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

W H Fung *MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
M H J Wessels *MS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. m.wessels@amsterdamumc.nl.ORCID http://orcid.org/0000-0003-2324-0499
E M E CoerverMS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
J de BeukelaarAlbert Schweitzer Hospital, Neurology, Dordrecht, The Netherlands.
W H BouvyDiakonessenhuis, Neurology, Utrecht, The Netherlands.
L R CantaCatharina Hospital, Neurology, Eindhoven, The Netherlands.
O H H GerlachZuyderland Medical Center, Neurology, Sittard-Geleen, The Netherlands, and School for Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.
E HoitsmaAlrijne Hospital, Neurology, Leiden, The Netherlands.
E L J HoogervorstSt. Antonius Hospital, Neurology, Utrecht, The Netherlands.
B A de JongMS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
N F KalkersOLVG, Neurology, Amsterdam, The Netherlands.
Z L E van KempenMS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
H LövenichSt. Jans Gasthuis, Neurology, Weert, The Netherlands.
C E P van MunsterAmphia Hospital, Neurology, Breda, The Netherlands.
B W van OostenMS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
J SmoldersErasmus Medical Center, MS center ErasMS, Neurology & Immunology, Rotterdam, The Netherlands.
A VennegoorFlevoziekenhuis, Neurology, Almere, The Netherlands.
E M P E ZeinstraIsala Hospital, Neurology, Meppel, The Netherlands.
M Barrantes-CepasMS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
G KooijMS Center Amsterdam, Molecular Cell Biology and Immunology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
M M SchoonheimMS Center Amsterdam, Anatomy and Neurosciences, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, location VUmc, Amsterdam, The Netherlands.
B I Lissenberg-WitteDepartment of Epidemiology and Data Science, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, The Netherlands.
B MoraalRadiology & Nuclear Medicine, MS Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
F BarkhofRadiology & Nuclear Medicine, MS Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
B M J UitdehaagMS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
J MostertRijnstate Hospital, Neurology, Arnhem, The Netherlands.
C E TeunissenNeurochemistry Laboratory, Department of Clinical Chemistry, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Amsterdam, The Netherlands.
J KillesteinMS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
E M M StrijbisMS Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam UMC location VUmc, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.

Funding

Stichting MS Research 17-992ZonMw 848043001
6 · The paper itself

Abstract

backgroundNeurofilament 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.

methodsLong-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.

results45(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.

Indexed as

Glial Fibrillary Acidic ProteinMultiple SclerosisMultiple Sclerosis, Relapsing-RemittingNeurofilament ProteinsAdultBiomarkersFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedReproducibility of ResultsBiomarkersGFAP protein, humanGlial Fibrillary Acidic Proteinneurofilament protein LNeurofilament ProteinsClinical trialsMRI in MSMS

Identifiers

PMID40699373
PMCPMC12287240

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.