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Treatment De-escalation in Relapsing-Remitting Multiple Sclerosis: An Observational Study
J. Müller, S. Sharmin, J. Lorscheider, D. Horakova, E. Kubala Havrdova, S. Eichau, F. Patti, P. Grammond, K. Buzzard, O. Skibina, A. Prat, M. Girard, F. Grand'Maison, R. Alroughani, J. Lechner-Scott, D. Spitaleri, M. Barnett, E. Cartechini, MJ....
Language English Country New Zealand
Document type Journal Article, Observational Study, Multicenter Study
Grant support
P500PM_214230
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
P5R5PM_225288
Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
2026836
National Health and Medical Research Council
- MeSH
- Adult MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Longitudinal Studies MeSH
- Recurrence MeSH
- Multiple Sclerosis, Relapsing-Remitting * drug therapy MeSH
- Retrospective Studies MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Observational Study MeSH
BACKGROUND: In 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. METHODS: In 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. RESULTS: Matching 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. CONCLUSIONS: On 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.
Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino Avellino Italy
Brain and Mind Centre Sydney Australia
CHUM MS Center Universite de Montreal Montreal Canada
CISSS Chaudière Appalache Levis Canada
CORe Department of Medicine University of Melbourne Melbourne VIC 3000 Australia
CSSS Saint Jérôme Saint Jerome QC Canada
Department of Medical and Surgical Sciences and Advanced Technologies GF Ingrassia Catania Italy
Department of Neurology Box Hill Hospital Melbourne Australia
Department of Neurology Hospital Universitario Virgen Macarena Sevilla Spain
Department of Neurology The Alfred Hospital Melbourne Australia
Department of Neurosciences Box Hill Hospital Melbourne Australia
Division of Neurology Department of Medicine Amiri Hospital Sharq Kuwait
Hospital Universitario Donostia San Sebastián Spain
Hunter Medical Research Institute University Newcastle Newcastle Australia
Neuro Rive Sud Longueuil QC Canada
Neuroimmunology Centre Department of Neurology Royal Melbourne Hospital Melbourne Australia
Neurology Institute Harley Street Medical Center Abu Dhabi UAE
Neurology Unit P O Unico Macerata ast Macerata Macerata Italy
References provided by Crossref.org
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