{
  "abstract": "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.\n\nMethods: 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.\n\nResults: 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.\n\nConclusions: 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.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 50,
  "authors": [
    {
      "name": "Valery Fuh-Ngwa"
    },
    {
      "name": "Amin Zarghami"
    },
    {
      "name": "Julie A. Campbell"
    },
    {
      "name": "Yuan Zhou"
    },
    {
      "name": "Ingrid van der Mei"
    },
    {
      "name": "Barbara Willekens"
    },
    {
      "name": "Tomas Kalincik"
    },
    {
      "name": "Laura L. Laslett"
    },
    {
      "name": "Jeannette Lechner-Scott"
    },
    {
      "name": "Serkan Ozakbas"
    },
    {
      "name": "Pierre Duquette"
    },
    {
      "name": "Oliver Gerlach"
    },
    {
      "name": "Davide Maimone"
    },
    {
      "name": "Riadh Gouider"
    },
    {
      "name": "Helmut Butzkueven"
    },
    {
      "name": "Patrice Lalive"
    },
    {
      "name": "Francesco Patti"
    },
    {
      "name": "Alexandre Prat"
    },
    {
      "name": "Marc Girard"
    },
    {
      "name": "Valentina Tomassini"
    },
    {
      "name": "Alessandra Lugaresi"
    },
    {
      "name": "Izanne Roos"
    },
    {
      "name": "Francois Grand’Maison"
    },
    {
      "name": "Raed Alroughani"
    },
    {
      "name": "Samia J. Khoury"
    },
    {
      "name": "Maria Pia Amato"
    },
    {
      "name": "Pierre Grammond"
    },
    {
      "name": "Vincent van Pesch"
    },
    {
      "name": "Daniele Spitaleri"
    },
    {
      "name": "Saloua Mrabet"
    },
    {
      "name": "Aysun Soysal"
    },
    {
      "name": "Ayse Altintas"
    },
    {
      "name": "Tamara Castillo-Triviño"
    },
    {
      "name": "Guy Laureys"
    },
    {
      "name": "Heidi Beadnall"
    },
    {
      "name": "Koen de Gans"
    },
    {
      "name": "Justin Garber"
    },
    {
      "name": "Anneke van der Walt"
    },
    {
      "name": "Claudio Solaro"
    },
    {
      "name": "Nevin John"
    },
    {
      "name": "José Luis Sánchez Menoyo"
    },
    {
      "name": "Julie Prevost"
    },
    {
      "name": "Abdullah Al-Asmi"
    },
    {
      "name": "Orla Gray"
    },
    {
      "name": "Tunde Csepany"
    },
    {
      "name": "Norma Deri"
    },
    {
      "name": "Stella Hughes"
    },
    {
      "name": "Foong Yi Chao"
    },
    {
      "name": "Bruce V. Taylor"
    },
    {
      "name": "the MSBase Study Group"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ecs5x18dh6zw2.bib",
  "cited_by": 0,
  "doi": "10.1186/s12916-026-05365-y",
  "fulltext_url": null,
  "id": "ecs5x18dh6zw2",
  "issns": [
    "1741-7015"
  ],
  "landing_url": "https://link.springer.com/article/10.1186/s12916-026-05365-y",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [],
  "openalex": null,
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-02",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/ecs5x18dh6zw2.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T00:25:23Z",
      "native_id": "10.1186/s12916-026-05365-y",
      "source": "crossref",
      "url": "https://link.springer.com/article/10.1186/s12916-026-05365-y"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:F27",
      "subfield": "general"
    }
  ],
  "title": "Disease-modifying therapies in managing disability worsening in adult relapsing multiple sclerosis: a population-based longitudinal study using the MSBase registry",
  "title_text": "Disease-modifying therapies in managing disability worsening in adult relapsing multiple sclerosis: a population-based longitudinal study using the MSBase registry",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T00:26:28Z",
  "url": "https://research.draconitic.com/paper/ecs5x18dh6zw2",
  "venue": "BMC Medicine",
  "versions": []
}