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Assessing the utility of magnetic resonance imaging-based "SuStaIn" disease subtyping for precision medicine in relapsing-remitting and secondary progressive multiple sclerosis.
- Source :
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Multiple sclerosis and related disorders [Mult Scler Relat Disord] 2023 Sep; Vol. 77, pp. 104869. Date of Electronic Publication: 2023 Jul 02. - Publication Year :
- 2023
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Abstract
- Background: Patient stratification and individualized treatment decisions based on multiple sclerosis (MS) clinical phenotypes are arbitrary. Subtype and Staging Inference (SuStaIn), a published machine learning algorithm, was developed to identify data-driven disease subtypes with distinct temporal progression patterns using brain magnetic resonance imaging; its clinical utility has not been assessed. The objective of this study was to explore the prognostic capability of SuStaIn subtyping and whether it is a useful personalized predictor of treatment effects of natalizumab and dimethyl fumarate.<br />Methods: Subtypes were available from the trained SuStaIn model for 3 phase 3 clinical trials in relapsing-remitting and secondary progressive MS. Regression models were used to determine whether baseline SuStaIn subtypes could predict on-study clinical and radiological disease activity and progression. Differences in treatment responses relative to placebo between subtypes were determined using interaction terms between treatment and subtype.<br />Results: Natalizumab and dimethyl fumarate reduced inflammatory disease activity in all SuStaIn subtypes (all p < 0.001). SuStaIn MS subtyping alone did not discriminate responder heterogeneity based on new lesion formation and disease progression (p > 0.05 across subtypes).<br />Conclusion: SuStaIn subtypes correlated with disease severity and functional impairment at baseline but were not predictive of disability progression and could not discriminate treatment response heterogeneity.<br />Competing Interests: Declaration of Competing Interest XJ, CS, BC, BZ, EF, SB, and ARG are employees of and hold stock/stock options in Biogen. DLA reports consulting fees from Celgene, EMD Serono, Frequency Therapeutics, MedDay, Merck, Novartis, Roche, and Sanofi, and research support from Biogen, Immunotec, and Novartis. CE reports speaker honoraria from EMD Serono and is an employee of NeuroRx.<br /> (Copyright © 2023. Published by Elsevier B.V.)
- Subjects :
- Humans
Dimethyl Fumarate pharmacology
Immunosuppressive Agents pharmacology
Magnetic Resonance Imaging methods
Natalizumab pharmacology
Precision Medicine
Multiple Sclerosis drug therapy
Multiple Sclerosis, Chronic Progressive diagnostic imaging
Multiple Sclerosis, Chronic Progressive drug therapy
Multiple Sclerosis, Relapsing-Remitting diagnostic imaging
Multiple Sclerosis, Relapsing-Remitting drug therapy
Multiple Sclerosis, Relapsing-Remitting pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2211-0356
- Volume :
- 77
- Database :
- MEDLINE
- Journal :
- Multiple sclerosis and related disorders
- Publication Type :
- Academic Journal
- Accession number :
- 37459715
- Full Text :
- https://doi.org/10.1016/j.msard.2023.104869