Brain volume loss in relapsing multiple sclerosis: indirect treatment comparisons of available disease-modifying therapies.

Autor: Zivadinov R; Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.; Center for Biomedical Imaging at the Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY, USA., Keenan AJ; Janssen Scientific Affairs, Janssen Pharmaceuticals, Titusville, NJ, USA. AKeenan1@its.jnj.com., Le HH; Janssen Scientific Affairs, Janssen Pharmaceuticals, Titusville, NJ, USA., Ait-Tihyaty M; Janssen Pharmaceuticals, Titusville, NJ, USA., Gandhi K; Janssen Pharmaceuticals, Titusville, NJ, USA., Zierhut ML; Certara USA, Inc., Radnor, PA, USA., Salvo-Halloran EM; EVERSANA, Value & Evidence Services, Burlington, ON, Canada., Ramirez AO; EVERSANA, Value & Evidence Services, Burlington, ON, Canada., Vuong V; EVERSANA, Value & Evidence Services, Burlington, ON, Canada., Singh S; EVERSANA, Value & Evidence Services, Burlington, ON, Canada., Hutton B; Ottawa Hospital Research Institute, Ottawa, ON, Canada.
Jazyk: angličtina
Zdroj: BMC neurology [BMC Neurol] 2024 Oct 08; Vol. 24 (1), pp. 378. Date of Electronic Publication: 2024 Oct 08.
DOI: 10.1186/s12883-024-03888-6
Abstrakt: Background: Brain volume loss (BVL) has been identified as a predictor of disability progression in relapsing multiple sclerosis (RMS). As many available disease-modifying treatments (DMTs) have shown an effect on slowing BVL, this is becoming an emerging clinical endpoint in RMS clinical trials.
Methods: In this study, a systematic literature review was conducted to identify BVL results from randomized controlled trials of DMTs in RMS. Indirect treatment comparisons (ITCs) were conducted to estimate the relative efficacy of DMTs on BVL using two approaches: a model-based meta-analysis (MBMA) with adjustment for measurement timepoint and DMT dosage, and a network meta-analysis (NMA).
Results: In the MBMA, DMTs associated with significantly reduced BVL versus placebo at two years included fingolimod (mean difference [MD] = 0.25; 95% confidence interval [CI] = 0.15 - 0.36), ozanimod (MD = 0.26; 95% CI = 0.12 - 0.41), teriflunomide (MD = 0.38; 95% CI = 0.20 - 0.55), alemtuzumab (MD = 0.38; 95% CI = 0.10 - 0.67) and ponesimod (MD = 0.71; 95% CI = 0.48 - 0.95), whereas interferons and natalizumab performed the most poorly. The results of NMA analysis were generally comparable with those of the MBMA.
Conclusions: Limitations of these analyses included the potential for confounding due to pseudoatrophy, and a lack of long-term clinical data for BVL. Our findings suggest that important differences in BVL may exist between DMTs. Continued investigation of BVL in studies of RMS is important to complement traditional disability endpoints, and to foster a better understanding of the mechanisms by which DMTs can slow BVL.
(© 2024. The Author(s).)
Databáze: MEDLINE
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