Disease-modifying therapies in managing disability worsening in adult relapsing multiple sclerosis: a population-based longitudinal study using the MSBase registry

@article{fuhngwa2026diseasemodifying,
  title = {{Disease-modifying therapies in managing disability worsening in adult relapsing multiple sclerosis: a population-based longitudinal study using the MSBase registry}},
  author = {Valery Fuh-Ngwa and Amin Zarghami and Julie A. Campbell and Yuan Zhou and Ingrid van der Mei and Barbara Willekens and Tomas Kalincik and Laura L. Laslett and Jeannette Lechner-Scott and Serkan Ozakbas and Pierre Duquette and Oliver Gerlach and Davide Maimone and Riadh Gouider and Helmut Butzkueven and Patrice Lalive and Francesco Patti and Alexandre Prat and Marc Girard and Valentina Tomassini and Alessandra Lugaresi and Izanne Roos and Francois Grand’Maison and Raed Alroughani and Samia J. Khoury and Maria Pia Amato and Pierre Grammond and Vincent van Pesch and Daniele Spitaleri and Saloua Mrabet and Aysun Soysal and Ayse Altintas and Tamara Castillo-Triviño and Guy Laureys and Heidi Beadnall and Koen de Gans and Justin Garber and Anneke van der Walt and Claudio Solaro and Nevin John and José Luis Sánchez Menoyo and Julie Prevost and Abdullah Al-Asmi and Orla Gray and Tunde Csepany and Norma Deri and Stella Hughes and Foong Yi Chao and Bruce V. Taylor and the MSBase Study Group},
  journal = {BMC Medicine},
  year = {2026},
  month = nov,
  doi = {10.1186/s12916-026-05365-y},
  url = {https://link.springer.com/article/10.1186/s12916-026-05365-y},
  note = {CC BY 4.0},
}

TY  - JOUR
TI  - Disease-modifying therapies in managing disability worsening in adult relapsing multiple sclerosis: a population-based longitudinal study using the MSBase registry
AU  - Valery Fuh-Ngwa
AU  - Amin Zarghami
AU  - Julie A. Campbell
AU  - Yuan Zhou
AU  - Ingrid van der Mei
AU  - Barbara Willekens
AU  - Tomas Kalincik
AU  - Laura L. Laslett
AU  - Jeannette Lechner-Scott
AU  - Serkan Ozakbas
AU  - Pierre Duquette
AU  - Oliver Gerlach
AU  - Davide Maimone
AU  - Riadh Gouider
AU  - Helmut Butzkueven
AU  - Patrice Lalive
AU  - Francesco Patti
AU  - Alexandre Prat
AU  - Marc Girard
AU  - Valentina Tomassini
AU  - Alessandra Lugaresi
AU  - Izanne Roos
AU  - Francois Grand’Maison
AU  - Raed Alroughani
AU  - Samia J. Khoury
AU  - Maria Pia Amato
AU  - Pierre Grammond
AU  - Vincent van Pesch
AU  - Daniele Spitaleri
AU  - Saloua Mrabet
AU  - Aysun Soysal
AU  - Ayse Altintas
AU  - Tamara Castillo-Triviño
AU  - Guy Laureys
AU  - Heidi Beadnall
AU  - Koen de Gans
AU  - Justin Garber
AU  - Anneke van der Walt
AU  - Claudio Solaro
AU  - Nevin John
AU  - José Luis Sánchez Menoyo
AU  - Julie Prevost
AU  - Abdullah Al-Asmi
AU  - Orla Gray
AU  - Tunde Csepany
AU  - Norma Deri
AU  - Stella Hughes
AU  - Foong Yi Chao
AU  - Bruce V. Taylor
AU  - the MSBase Study Group
PY  - 2026
DA  - 2026/11/02
JO  - BMC Medicine
DO  - 10.1186/s12916-026-05365-y
UR  - https://link.springer.com/article/10.1186/s12916-026-05365-y
AB  - Background: Disease-modifying therapies (DMTs) reduce inflammatory activity in relapsing multiple sclerosis (MS), yet their long-term effects on disability worsening, and how these vary by age at treatment initiation in routine clinical practice, remain uncertain. We examined age-dependent associations of DMTs with disability progression across clinically meaningful Expanded Disability Status Scale (EDSS) states, including secondary progressive MS (SPMS), while accounting for latent heterogeneity in progression risk.  Methods: We analysed longitudinal data from the international MSBase registry, including adults with relapse-onset MS (symptom onset ≥ 18 years), ≥ 12 months of follow-up, and ≥ 2 EDSS scores recorded remote from relapse. Disability progression was defined as transitions between five EDSS-based states: nil/minimal (0–1.5), mild (2.0–2.5), moderate (3.0–3.5), gait disability (≥ 4.0), and SPMS. A continuous-time random-effects multistate model jointly estimated worsening and improvement transitions. Associations of low-efficacy and high-efficacy DMTs versus no treatment were assessed with age-by-treatment interactions. Age-stratified treatment effects were summarised as 5-year percentage inhibition of disability progression (%IDP). Random-effects captured unobserved between-person heterogeneity and identified latent progression subgroups.  Results: Among 15,425 participants (70.9% female), median follow-up was 9.4 years (IQR 4.7–15.6). Overall, 87.9% received DMTs, with 48.7% initiating high-efficacy and 45.9% initiating low-efficacy therapy. Both DMT classes were associated with more favourable disability trajectories across most transitions, including increased likelihood of improvement. Treatment effects were strongly age-dependent, with greatest benefit in younger adults (18–30 years), attenuation through midlife (30–50 years), and weaker or inconclusive effects after age 50, particularly for transitions to SPMS. In 5-year %IDP analyses, inhibitory effects declined monotonically with age. High-efficacy therapy conferred greater inhibition of disability progression than low-efficacy therapy, with evidence of benefit persisting into older age. Two latent subgroups were identified: a rapid-worsening group (76.1%) and a stable/improving group (23.9%), differing markedly in progression hazards and recovery potential.  Conclusions: In this large real-world cohort, DMTs were associated with sustained but age-dependent reductions in disability progression. Substantial heterogeneity in progression risk supports personalised treatment strategies, improved risk stratification, and enriched clinical trial design.
SN  - 1741-7015
ER  -