Treatment effect modifiers of immunotherapies for relapsing-remitting multiple sclerosis—A systematic review and meta-analysis

Other authors

Institut Català de la Salut

[Heesen C] Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center, Hamburg, Germany. Department of Neurology, University Medical Center, Hamburg, Germany. [Röver C, Salem S, Heinz J] Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany. [Chard D] Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK National Institute for Health Research (NIHR), University College London Hospitals (UCLH) Biomedical Research Centre, London, UK. [Rio J] Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Multiple de Catalunya (CEMCAT), Barcelona, Spain. Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain

Vall d'Hebron Barcelona Hospital Campus

Publication date

2024-12-27T12:00:37Z

2024-12-27T12:00:37Z

2024-10-24



Abstract

Multiple sclerosis; Disease-modifying therapy; Treatment response


Esclerosi múltiple; Teràpia modificadora de la malaltia; Resposta al tractament


Esclerosis múltiple; Terapia modificadora de la enfermedad; Respuesta al tratamiento


Abstract Background This meta-analysis aimed to assess the treatment effects of immunotherapies in subgroups of adults with clinically isolated syndrome or relapsing forms of multiple sclerosis (MS) and the effect of potential treatment effect modifiers (TEMs). Methods Phase 2 and 3 RCTs with a placebo comparator were analyzed. Risk of bias was assessed. Random-effects meta-analyses were conducted to summarize treatment effects within subgroups and differences in treatment effects between subgroups. Results Thirty-one studies were included. Age < 40 years was the strongest TEM for relapse rate across DMTs with a ratio of rate ratios (RRR) of 1.44 (95% CI 1.09–1.90; 7 studies). Disability progression was influenced by age (ratio of hazard ratios, RHR 1.59, 95% CI 1.11–2.29; 4 studies). Dichotomizing patients based on EDSS cut-offs (EDSS 2.0 and 3.0) also showed a significantly higher benefit for those less disabled for relapse rate (RRR 1.35, CI 1.03–1.76; 8 studies). Sex, baseline MRI parameters, previous immunotherapy, and clinical presentation showed no effect in this meta-analysis. Conclusion Age < 40 is a robust TEM for a lower relapse rate as well as less disability progression across six MS immunotherapies. Additionally, a lower baseline EDSS was predictive of the relapse rate.


This work was supported by the Federal Ministry of Education and Research (grant number 01KG1804).

Document Type

Article


Published version

Language

English

Publisher

SAGE Publications

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Attribution-NonCommercial 4.0 International

http://creativecommons.org/licenses/by-nc/4.0/

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