Multiple sclerosis and related disorders · 2023
Assessing the utility of magnetic resonance imaging-based "SuStaIn" disease subtyping for precision medicine in relapsing-remitting and secondary progressive multiple sclerosis.
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Jiang Xiaotong, Shen Changyu, Caba Bastien, Arnold Douglas L, Elliott Colm, Zhu Bing, Fisher Elizabeth, Belachew Shibeshih, Gafson Arie R
Аннотация
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.
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.
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).
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.
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.
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).
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.