Evidence map›Paper›PMID 39953338›Full record

Observational studyCNS drugs2025

Treatment De-escalation in Relapsing-Remitting Multiple Sclerosis: An Observational Study.

Jannis Müller, Sifat Sharmin, Johannes Lorscheider, Dana Horakova, Eva Kubala Havrdova, Sara Eichau, Francesco Patti, Pierre Grammond, Katherine Buzzard, Olga Skibina and 24 more

Abstract readObservational StudyMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in CNS drugs, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. The Art of Sequencing Disease-Modifying Therapies in Multiple Sclerosis.Neurology(R) neuroimmunology & neuroinflammation · 2026
    Review
  2. Big data in multiple sclerosis.Current opinion in neurology · 2026
    Review
  3. Article
  4. Article
  5. Article
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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

34 authors.

Jannis MüllerCORe, Department of Medicine, University of Melbourne, Melbourne, VIC, 3000, Australia.
Sifat SharminCORe, Department of Medicine, University of Melbourne, Melbourne, VIC, 3000, Australia.
Johannes LorscheiderNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
Dana HorakovaDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
Eva Kubala HavrdovaDepartment of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University in Prague and General University Hospital, Prague, Czech Republic.
Sara EichauDepartment of Neurology, Hospital Universitario Virgen Macarena, Sevilla, Spain.
Francesco PattiDepartment of Medical and Surgical Sciences and Advanced Technologies, GF Ingrassia, Catania, Italy.
Pierre GrammondCISSS Chaudière-Appalache, Levis, Canada.
Katherine BuzzardDepartment of Neurosciences, Box Hill Hospital, Melbourne, Australia.
Olga SkibinaDepartment of Neurology, Box Hill Hospital, Melbourne, Australia.
Alexandre PratCHUM MS Center, Universite de Montreal, Montreal, Canada.
Marc GirardCHUM MS Center, Universite de Montreal, Montreal, Canada.
Francois Grand'MaisonNeuro Rive-Sud, Longueuil, QC, Canada.
Raed AlroughaniDivision of Neurology, Department of Medicine, Amiri Hospital, Sharq, Kuwait.
Jeannette Lechner-ScottHunter Medical Research Institute, University Newcastle, Newcastle, Australia.
Daniele SpitaleriAzienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino, Avellino, Italy.
Michael BarnettBrain and Mind Centre, Sydney, Australia.
Elisabetta CartechiniNeurology Unit, P O Unico Macerata, ast Macerata, Macerata, Italy.
Maria Jose SaDepartment of Neurology, Centro Hospitalar Universitario de Sao Joao, and Faculty of Health Sciences, University Fernando Pessoa, Porto, Portugal.
Oliver GerlachAcademic MS Center Zuyd, Department of Neurology, Zuyderland Medical Center, Sittard-Geleen, The Netherlands.
Anneke van der WaltDepartment of Neurology, The Alfred Hospital, Melbourne, Australia.
Helmut ButzkuevenDepartment of Neurology, The Alfred Hospital, Melbourne, Australia.
Julie PrevostCSSS Saint-Jérôme, Saint-Jerome, QC, Canada.
Tamara Castillo-TriviñoHospital Universitario Donostia, San Sebastián, Spain.
Bassem YamoutNeurology Institute, Harley Street Medical Center, Abu Dhabi, UAE.
Samia J KhouryNehme and Therese Tohme Multiple Sclerosis Center, American University of Beirut Medical Center, Beirut, Lebanon.
Özgür YaldizliNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
Tobias DerfussNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
Cristina GranzieraNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
Jens KuhleNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
Ludwig KapposNeurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland.
Izanne Roos *CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, 3000, Australia.
Tomas Kalincik *CORe, Department of Medicine, University of Melbourne, Melbourne, VIC, 3000, Australia. tomas.kalincik@unimelb.edu.au.ORCID http://orcid.org/0000-0003-3778-1376
MSBase Study Group

Funding

National Health and Medical Research Council 2026836Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung P500PM_214230Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung P5R5PM_225288
6 · The paper itself

Abstract

backgroundIn relapsing-remitting multiple sclerosis (RRMS), extended exposure to high-efficacy disease modifying therapy may increase the risk of side effects, compromise treatment adherence, and inflate medical costs. Treatment de-escalation, here defined as a switch to a lower efficacy therapy, is often considered by patients and physicians, but evidence to guide such decisions is scarce. In this study, we aimed to compare clinical outcomes between patients who de-escalated therapy versus those who continued their therapy.

methodsIn this retrospective analysis of data from an observational, longitudinal cohort of 87,239 patients with multiple sclerosis (MS) from 186 centers across 43 countries, we matched treatment episodes of adult patients with RRMS who underwent treatment de-escalation from either high- to medium-, high- to low-, or medium- to low-efficacy therapy with counterparts that continued their treatment, using propensity score matching and incorporating 11 variables. Relapses and 6-month confirmed disability worsening were assessed using proportional and cumulative hazard models.

resultsMatching resulted in 876 pairs (de-escalators: 73% females, median [interquartile range], age 40.2 years [33.6, 48.8], Expanded Disability Status Scale [EDSS] 2.5 [1.5, 4.0]; non-de-escalators: 73% females, age 40.8 years [35.5, 47.9], and EDSS 2.5 [1.5, 4.0]), with a median follow-up of 4.8 years (IQR 3.0, 6.8). Patients who underwent de-escalation faced an increased hazard of future relapses (hazard ratio 2.36 and 95% confidence intervals [CI] [1.79-3.11], p < 0.001), which was confirmed when considering recurrent relapses (2.43 [1.97-3.00], p < 0.001). It was also consistent across subgroups stratified by age, sex, disability, disease duration, and time since last relapse.

conclusionsOn the basis of this observational analysis, de-escalation may not be recommended as a universal treatment strategy in RRMS. The decision to de-escalate should be considered on an individual basis, as its safety is not clearly guided by specific patient or disease characteristics evaluated in this study.

Indexed as

Multiple Sclerosis, Relapsing-RemittingAdultFemaleHumansLongitudinal StudiesMaleMiddle AgedRetrospective StudiesTreatment Outcome

Identifiers

PMID39953338
PMCPMC11909097

What OpenQuestion holds

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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.