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The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study

The indirect contribution of multiple sclerosis (MS) relapses to disability worsening outcomes, and vice-versa, remains unclear. Disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights into disease pathoge...

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Autores principales: Fuh-Ngwa, Valery, Charlesworth, Jac C., Zhou, Yuan, van der Mei, Ingrid, Melton, Phillip E., Broadley, Simon A., Ponsonby, Anne-Louise, Simpson-Yap, Steve, Lechner-Scott, Jeannette, Taylor, Bruce V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354053/
https://www.ncbi.nlm.nih.gov/pubmed/37463930
http://dx.doi.org/10.1038/s41598-023-38415-z
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author Fuh-Ngwa, Valery
Charlesworth, Jac C.
Zhou, Yuan
van der Mei, Ingrid
Melton, Phillip E.
Broadley, Simon A.
Ponsonby, Anne-Louise
Simpson-Yap, Steve
Lechner-Scott, Jeannette
Taylor, Bruce V.
author_facet Fuh-Ngwa, Valery
Charlesworth, Jac C.
Zhou, Yuan
van der Mei, Ingrid
Melton, Phillip E.
Broadley, Simon A.
Ponsonby, Anne-Louise
Simpson-Yap, Steve
Lechner-Scott, Jeannette
Taylor, Bruce V.
author_sort Fuh-Ngwa, Valery
collection PubMed
description The indirect contribution of multiple sclerosis (MS) relapses to disability worsening outcomes, and vice-versa, remains unclear. Disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights into disease pathogenesis and treatment practice in relapse-onset MS (ROMS). Utilising a unique, prospectively collected clinical data from a longitudinal cohort of 279 first demyelinating event cases followed for up to 15 years post-onset, we examined indirect associations between relapses and treatment and the risk of disability worsening, and vice-versa. Indirect association parameters were estimated using joint models for longitudinal and survival data. Early relapses within 2.5 years of MS onset predicted early disability worsening outcomes (HR = 3.45, C.I 2.29–3.61) per relapse, but did not contribute to long-term disability worsening thereinafter (HR = 0.21, C.I 0.15–0.28). Conversely, disability worsening outcomes significantly contributed to relapse risk each year (HR = 2.96, C.I 2.91–3.02), and persisted over time (HR = 3.34, C.I 2.90–3.86), regardless of DMT treatments. The duration of DMTs significantly reduced the hazards of relapses (1st-line DMTs: HR = 0.68, C.I 0.58–0.79; 3rd-line DMTs: HR = 0.37, C.I 0.32–0.44) and disability worsening events (1st-line DMTs: HR = 0.74, C.I 0.69–0.79; 3rd-line DMTs: HR = 0.90, C.I 0.85–0.95), respectively. Results from time-dynamic survival probabilities further revealed individuals having higher risk of future relapses and disability worsening outcomes, respectively. The study provided evidence that in ROMS, relapses accrued within 2.5 years of MS onset are strong indicators of disability worsening outcomes, but late relapses accrued 2.5 years post onset are not overt risk factors for further disability worsening. In contrast, disability worsening outcomes are strong positive predictors of current and subsequent relapse risk. Long-term DMT use and older age strongly influence the individual outcomes and their associations.
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spelling pubmed-103540532023-07-20 The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study Fuh-Ngwa, Valery Charlesworth, Jac C. Zhou, Yuan van der Mei, Ingrid Melton, Phillip E. Broadley, Simon A. Ponsonby, Anne-Louise Simpson-Yap, Steve Lechner-Scott, Jeannette Taylor, Bruce V. Sci Rep Article The indirect contribution of multiple sclerosis (MS) relapses to disability worsening outcomes, and vice-versa, remains unclear. Disease modifying therapies (DMTs) are potential modulators of this association. Understanding how these endo-phenotypes interact may provide insights into disease pathogenesis and treatment practice in relapse-onset MS (ROMS). Utilising a unique, prospectively collected clinical data from a longitudinal cohort of 279 first demyelinating event cases followed for up to 15 years post-onset, we examined indirect associations between relapses and treatment and the risk of disability worsening, and vice-versa. Indirect association parameters were estimated using joint models for longitudinal and survival data. Early relapses within 2.5 years of MS onset predicted early disability worsening outcomes (HR = 3.45, C.I 2.29–3.61) per relapse, but did not contribute to long-term disability worsening thereinafter (HR = 0.21, C.I 0.15–0.28). Conversely, disability worsening outcomes significantly contributed to relapse risk each year (HR = 2.96, C.I 2.91–3.02), and persisted over time (HR = 3.34, C.I 2.90–3.86), regardless of DMT treatments. The duration of DMTs significantly reduced the hazards of relapses (1st-line DMTs: HR = 0.68, C.I 0.58–0.79; 3rd-line DMTs: HR = 0.37, C.I 0.32–0.44) and disability worsening events (1st-line DMTs: HR = 0.74, C.I 0.69–0.79; 3rd-line DMTs: HR = 0.90, C.I 0.85–0.95), respectively. Results from time-dynamic survival probabilities further revealed individuals having higher risk of future relapses and disability worsening outcomes, respectively. The study provided evidence that in ROMS, relapses accrued within 2.5 years of MS onset are strong indicators of disability worsening outcomes, but late relapses accrued 2.5 years post onset are not overt risk factors for further disability worsening. In contrast, disability worsening outcomes are strong positive predictors of current and subsequent relapse risk. Long-term DMT use and older age strongly influence the individual outcomes and their associations. Nature Publishing Group UK 2023-07-18 /pmc/articles/PMC10354053/ /pubmed/37463930 http://dx.doi.org/10.1038/s41598-023-38415-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Fuh-Ngwa, Valery
Charlesworth, Jac C.
Zhou, Yuan
van der Mei, Ingrid
Melton, Phillip E.
Broadley, Simon A.
Ponsonby, Anne-Louise
Simpson-Yap, Steve
Lechner-Scott, Jeannette
Taylor, Bruce V.
The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study
title The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study
title_full The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study
title_fullStr The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study
title_full_unstemmed The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study
title_short The association between disability progression, relapses, and treatment in early relapse onset MS: an observational, multi-centre, longitudinal cohort study
title_sort association between disability progression, relapses, and treatment in early relapse onset ms: an observational, multi-centre, longitudinal cohort study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10354053/
https://www.ncbi.nlm.nih.gov/pubmed/37463930
http://dx.doi.org/10.1038/s41598-023-38415-z
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