Evidence map›Paper›PMID 42002655›Full record

ArticleJournal of neurology2026

Predicting disease progression in multiple sclerosis with clinically accessible information and technology.

Tom A N Fuchs, Menno M Schoonheim, Eva M M Strijbis, Julia R Jelgerhuis, Dana Horakova, Eva K Havrdova, Tomas Uher, Robert Zivadinov, Serkan Ozakbas, Marc Girard and 65 more

Abstract readMulticenter Study
In one paragraph

Article in Journal of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. 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

75 authors.

Tom A N FuchsMS Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, Location VUmc, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands. t.fuchs@amsterdamumc.nl.ORCID http://orcid.org/0000-0002-0219-3518
Menno M SchoonheimMS Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, Location VUmc, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Eva M M StrijbisMS Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, Location VUmc, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Julia R JelgerhuisMS Center Amsterdam, Vrije Universiteit Amsterdam, Amsterdam UMC, Location VUmc, De Boelelaan 1108, 1081 HZ, Amsterdam, The Netherlands.
Dana HorakovaCharles University in Prague and General University Hospital, Prague, Czech Republic.
Eva K HavrdovaCharles University in Prague and General University Hospital, Prague, Czech Republic.
Tomas UherCharles University in Prague and General University Hospital, Prague, Czech Republic.
Robert ZivadinovJacobs School of Medicine and Biomedical Sciences, Buffalo, USA.
Serkan OzakbasIzmir University of Economics, Medical Point Hospital, Izmir, Turkey.
Marc GirardCHUM and Universite de Montreal, Montreal, Canada.
Raed AlroughaniAmiri Hospital, Sharq, Kuwait.
Pierre GrammondCISSS Chaudière-Appalache, Levis, Canada.
Alessandra LugaresiUniversità di Bologna, Bologna, Italia.
Valentina TomassiniUniversity G. d'Annunzio of Chieti-Pescara, Chieti, Italy.
Tomas KalincikDepartment of Neurology, Neroimmunology Centre, Royal Melbourne Hospital, Melbourne, Australia.
Izanne RoosDepartment of Neurology, Neroimmunology Centre, Royal Melbourne Hospital, Melbourne, Australia.
Oliver GerlachZuyderland Medical Center, Sittard-Geleen, The Netherlands.
Anneke van der WaltDepartment of Neurology, The Alfred Hospital, Melbourne, Australia.
Samia J KhouryAmerican University of Beirut Medical Center, Beirut, Lebanon.
Vincent van PeschCliniques Universitaires Saint-Luc, Brussels, Belgium.
Andrea SurcinelliS. Maria Delle Croci Hospital, AUSL Romagna, Ravenna, Italy.
Matteo FoschiS. Maria Delle Croci Hospital, AUSL Romagna, Ravenna, Italy.
Maria Jose SaCentro Hospitalar Universitario de Sao Joao, Porto, Portugal.
Emanuelle D'amicoMedical and Surgical Sciences, Universita di Foggia, Foggia, Italy.
Jens KuhleUniversity Hospital Basel, Basel, Switzerland.
Elisabetta CartechiniNeurology Unit, AST Macerata, Macerata, Italy.
Davide MaimoneAzienda Ospedaliera per l'Emergenza Cannizzaro, Catania, Italy.
Rana KarabudakYeditepe University, Istanbul, Turkey.
Aysun SoysalBakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases, Istanbul, Turkey.
Daniele SpitaleriAzienda Ospedaliera di rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.
Guy LaureysUniversitary Hospital Ghent, Ghent, Belgium.
Bruce TaylorRoyal Hobart Hospital, Hobart, Australia.
Marie D'hoogheNational MS Centrum, Melsbroek, Belgium.
Radek AmpapaNemocnice Jihlava, Jihlava, Czech Republic.
Tamara Castillo-TriviñoHospital Universitario Donostia and IIS Biodonostia, San Sebastián, Spain.
Ayse AltintasKoc University, Istanbul, Turkey.
Orla GraySouth Eastern HSC Trust, Belfast, UK.
Riadh GouiderRazi University Hospital, Tunis, Tunisia.
Jose E Meca-LallanaVirgen de la Arrixaca Clinical University Hospital. IMIB-Arrixaca, Murcia, Spain.
Allan G KermodePerron Institute for Neurological and Translational Science, The University of Western Australia, Perth, Australia.
Marzena Fabis-PedriniPerron Institute for Neurological and Translational Science, The University of Western Australia, Perth, Australia.
William M CarrollPerron Institute for Neurological and Translational Science, The University of Western Australia, Perth, Australia.
Koen de GansGroene Hart Ziekenhuis, Gouda, The Netherlands.
Jose Luis Sanchez-MenoyoGaldakao-Usansolo University Hospital, Osakidetza-Basque Health Service, Galdakao, Spain.
Masoud EtemadifarMS Institute, Osfahan, Iran.
Abdullah Al-AsmiCollege of Medicine and Health Sciences and Sultan, Qaboos University Hospital, Sultan Qaboos University, Al-Khodh, Oman.
Pamela McCombeRoyal Brisbane and Women's Hospital, Brisbane, Australia.
Mihaela SimuDepartment of Neuroscience Clinic of Neurology, University of Medicine and Pharmacy Victor Babes Timisoara, Timisoara, Romania.
Mehmet Fatih YetkinDepartment of Neurology, Erciyes University, Kayseri, Turkey.
Talal Al-HarbiKing Fahad Specialist Hospital-Dammam, Dammam, Saudi Arabia.
Tunde CsepanyDepartment of Neurology, University of Debrecen, Debrecen, Hungary.
Patrice LaliveFaculty of Medicine, Geneva University Hospitals, Geneva, Switzerland.
Todd A HardyConcord Repatriation General Hospital, University of Sydney, Sydney, Australia.
Sudarshini RamanathanConcord Repatriation General Hospital, University of Sydney, Sydney, Australia.
Barbara WillekensDepartment of Neurology, Antwerp University Hospital, Edegem, Belgium.
Angel Perez SempereHospital General Universitario de Alicante, Alicante, Spain.
Simón Cárdenas-RobledoHospital Universitario Nacional de Colombia, Bogota, Colombia.
Mario HabekUniversity Hospital Center Zagreb, Zagreb, Croatia.
Bhim SinghalBombay Hospital Institute of Medical Sciences, Mumbai, India.
Nikolaos GrigoriadisAHEPA University Hospital, Thessaloniki, Greece.
Magdolna SimoSemmelweis University Budapest, Budapest, Hungary.
Vahid ShaygannejadIsfahan University of Medical Sciences, Isfahan, Iran.
Yolanda BlancoHospital Clinic de Barcelona, Barcelona, Spain.
Eduardo Aguera-MoralesUniversity of Cordoba, Cordoba, Spain.
Justin GarberDepartment of Neurology, Westmead Hospital, Sydney, Australia.
Claudio SolaroDepartment of Neurology, Galliera Hospital, Genoa, Italy.
Neil ShueyVincent's Hospital, Fitzroy, ,Melbourne, Australia.
Dheeraj KhuranaDepartment of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Danny DecooAlma Ziekenhuis, Sijsele, Damme, Belgium.
Abdorreza Naser MoghadasiMultiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Katherine BuzzardDepartment of Neurosciences, Box Hill Hospital, Box Hill, Melbourne, Australia.
Olga SkibinaDepartment of Neurosciences, Box Hill Hospital, Box Hill, Melbourne, Australia.
Nevin JohnDepartment of Neurology, Monash University, Clayton, Australia.
Thor PetersenAarhus University Hospital, Arhus C, Denmark.
Bianca Weinstock-GuttmanJacobs School of Medicine and Biomedical Sciences, Buffalo, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPredicting disease progression at the individual level is essential for personalized medicine. We previously developed machine-learning tools to estimate 5-year progression risk in people with multiple sclerosis (PwMS). Such models should account for disease-modifying therapy (DMT) and objective outcome definitions.

methodsIn a retrospective multicenter case-control study, we evaluated adults with relapsing-remitting multiple sclerosis (RRMS) at baseline. Using machine-learning, we developed two complementary tools for individualized 5-year risk estimation: DAAE-M, optimized for transparency, software-neutral use, and mitigation of indication bias, and ELIE, optimized for dynamic landmark-based modeling, complex treatment histories, and mitigation of immortal-time bias. Disease progression was defined using both a clinical outcome (RRMS-to-progressive MS) and an objective outcome (late-stage confirmed progression independent of relapse activity).

resultsAmong 34,510 people with RRMS (72.6% female, mean age = 37.1, mean disease duration = 5.8), 9.8% and 21% met clinical and objective progression criteria, respectively, over five years. Both models demonstrated good calibration across risk-groups (Brier scores 0.06-0.16). DAAE-M provided patient-level risk estimates with monotonic risk escalation across risk-groups for clinical (3.1%/11.2%/22.6%/33.0%) and objective (8.4%/14.5%/23.3%/38.8%) progression. For DAAE-M, high-efficacy DMT was associated with approximately half the progression risk compared with low-efficacy DMT (risk-ratios: 0.42-0.59; p < 0.01). ELIE also showed good calibration across risk deciles with increasing incidence for both clinical (0.3%/1.2%/1.7%/2.5%/3.7%/5.5%/7.2%/10.2%/14.3%/21.5%) and objective (0.9%/1.6%/2.5%/4.0%/5.8%/7.8%/10.2%/15.3%/20.9%/32.5%) outcomes.

conclusionWe developed two well-calibrated machine-learning-based tools for individualized 5-year prediction of clinically- and objectively-defined MS progression, each with distinct strengths in usability, bias handling, and treatment modeling. These findings support future tool use in personalized risk stratification and secondary prevention.

Indexed as

Disease ProgressionMachine LearningMultiple Sclerosis, Relapsing-RemittingAdultCase-Control StudiesFemaleHumansMaleMiddle AgedPredictive Learning ModelsRetrospective StudiesClinicalDecision support toolsDisease progressionMultiple sclerosisPredictionSecondary progressive multiple sclerosis

Identifiers

PMID42002655
PMCPMC13092528

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Registered trials

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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.