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Background and Objectives <p>Patients aged ≥&#xa0;35 years at multiple sclerosis (MS) symptom onset with an Expanded Disability Status Scale (EDSS) score ≥&#xa0;3 within the first year are at highest risk of developing aggressive MS (EDSS ≥&#xa0;6 within 10 years). Patients without these features are at lowest risk. This study aimed to evaluate whether high-efficacy disease-modifying therapy (HE-DMT) reduced the risk of relapse and disability accumulation in individuals at high risk of aggressive MS, and whether treatment benefit varied by MS severity.</p> Methods <p>This observational cohort study used longitudinal data from two registries: MSBase (international) and OFSEP (France). Adults with relapse-onset MS and an EDSS score recorded within 12 months of symptom onset were included. Patients were classified into high-risk or low-risk groups for aggressive MS based on the above strata; those at intermediate risk were excluded. A pseudo-cohort framework compared periods of continuous HE-DMT (fingolimod, cladribine, monoclonal antibodies) with periods of non-HE-DMT states (on lower-efficacy DMTs or untreated) within each aggressive MS risk stratum. Marginal structural models with repeated adjustment for time-varying confounders of treatment and censoring were used to estimate counterfactual cumulative hazards of relapses and 6-month confirmed disability worsening and improvement. An interaction between MS risk stratum and treatment strategy was tested. A secondary analysis evaluated patients who received an HE-DMT during the study period.</p> Results <p>In total, 10,405 people (2021 high risk, 8384 low risk) were included. Continuous HE-DMT reduced the risk of relapse in both high-risk and low-risk groups. There was no evidence of a difference in disability outcomes between treatment approaches. There was no evidence of an interaction between aggressive MS risk and treatment effect. In stratified analyses, lowest relapse risk was observed in the low-risk group treated with HE-DMT (hazard ratio [HR] 0.75, 95% CI 0.69–0.80). Treatment with HE-DMT was associated with relapse risk comparable to that observed in the low-risk group not treated with HE-DMT (HR 0.99, 0.87–1.13). In a secondary analysis restricted to patients who receive HE-DMT during the study timeframe, treatment with HE-DMT reduced the risk of disability worsening in the high-risk group (HR 0.75, 0.58–0.99), to the level observed in the low-risk group (HR 0.80, 0.70–0.92).</p> Conclusions <p>HE-DMTs reduced the risk of relapse in people at both high and low risk of aggressive MS, with no evidence of differential treatment benefit. In the overall population, no evidence of a difference in disability outcomes between HE-DMT-treated and HE-DMT-untreated time was observed. However, among patients ever exposed to HE-DMT, disability worsening was less common while treated with HE-DMT.</p>

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Preserving Neurological Function in People at High and Low Risk of Aggressive Multiple Sclerosis: An Observational Cohort Study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月4日

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  • Izanne Roos,
  • Sifat Sharmin,
  • Serkan Ozakbas,
  • Raed Alroughani,
  • Sara Eichau,
  • Francois Grand’Maison,
  • Cavit Boz,
  • Jeannette Lechner-Scott,
  • Katherine Buzzard,
  • Alexandre Prat,
  • Samia J. Khoury,
  • Pierre Grammond,
  • Anneke van der Walt,
  • Yolanda Blanco,
  • Matteo Foschi,
  • Aysun Soysal,
  • Michael Barnett,
  • Julie Prevost,
  • Murat Terzi,
  • Oliver Gerlach,
  • Richard Macdonell,
  • Maria Jose Sa,
  • Daniele Spitaleri,
  • Guy Laureys,
  • Vincent van Pesch,
  • Nevin John,
  • Elisabetta Cartechini,
  • Riadh Gouider,
  • Davide Maimone,
  • Cristina Ramo-Tello,
  • Suzanne Hodgkinson,
  • Mark Slee,
  • Pamela McCombe,
  • Justin Garber,
  • Jose Luis Sanchez-Menoyo,
  • Abdullah Al-Asmi,
  • Allan G. Kermode,
  • Emmanuelle Lapointe,
  • Vahid Shaygannejad,
  • Bart Van Wijmeersch,
  • Barbara Willekens,
  • Tamara Castillo-Triviño,
  • Bruce Taylor,
  • Guillaume Mathey,
  • Emmanuelle Le Page,
  • Jerome De Seze,
  • Aurelie Ruet,
  • Pierre Clavelou,
  • Eric Berger,
  • Helene Zephir,
  • Arnaud Kwiatkowski,
  • Jean Pelletier,
  • Thibault Moreau,
  • Pierre Labauge,
  • Jonathan Ciron,
  • Christine Lebrun-Frenay,
  • Caroline Papeix,
  • Gilles Defer,
  • David Axel Laplaud,
  • Eric Thouvenot,
  • Bruno Stankoff,
  • Elisabeth Maillart,
  • Abdullatif Al-Khedr,
  • Bertrand Bourre,
  • Olivier Casez,
  • Amélie Dos Santos,
  • Jean-Philippe Camdessanche,
  • Karolina Hankiewicz,
  • Abir Wahab,
  • Philippe Cabre,
  • Olivier Heinzlef,
  • Corinne Pottier,
  • Solène Moulin,
  • Laurent Magy,
  • Céline Labeyrie,
  • Inès Doghri,
  • Sandra Vukusic,
  • Tomas Kalincik

摘要

Background and Objectives

Patients aged ≥ 35 years at multiple sclerosis (MS) symptom onset with an Expanded Disability Status Scale (EDSS) score ≥ 3 within the first year are at highest risk of developing aggressive MS (EDSS ≥ 6 within 10 years). Patients without these features are at lowest risk. This study aimed to evaluate whether high-efficacy disease-modifying therapy (HE-DMT) reduced the risk of relapse and disability accumulation in individuals at high risk of aggressive MS, and whether treatment benefit varied by MS severity.

Methods

This observational cohort study used longitudinal data from two registries: MSBase (international) and OFSEP (France). Adults with relapse-onset MS and an EDSS score recorded within 12 months of symptom onset were included. Patients were classified into high-risk or low-risk groups for aggressive MS based on the above strata; those at intermediate risk were excluded. A pseudo-cohort framework compared periods of continuous HE-DMT (fingolimod, cladribine, monoclonal antibodies) with periods of non-HE-DMT states (on lower-efficacy DMTs or untreated) within each aggressive MS risk stratum. Marginal structural models with repeated adjustment for time-varying confounders of treatment and censoring were used to estimate counterfactual cumulative hazards of relapses and 6-month confirmed disability worsening and improvement. An interaction between MS risk stratum and treatment strategy was tested. A secondary analysis evaluated patients who received an HE-DMT during the study period.

Results

In total, 10,405 people (2021 high risk, 8384 low risk) were included. Continuous HE-DMT reduced the risk of relapse in both high-risk and low-risk groups. There was no evidence of a difference in disability outcomes between treatment approaches. There was no evidence of an interaction between aggressive MS risk and treatment effect. In stratified analyses, lowest relapse risk was observed in the low-risk group treated with HE-DMT (hazard ratio [HR] 0.75, 95% CI 0.69–0.80). Treatment with HE-DMT was associated with relapse risk comparable to that observed in the low-risk group not treated with HE-DMT (HR 0.99, 0.87–1.13). In a secondary analysis restricted to patients who receive HE-DMT during the study timeframe, treatment with HE-DMT reduced the risk of disability worsening in the high-risk group (HR 0.75, 0.58–0.99), to the level observed in the low-risk group (HR 0.80, 0.70–0.92).

Conclusions

HE-DMTs reduced the risk of relapse in people at both high and low risk of aggressive MS, with no evidence of differential treatment benefit. In the overall population, no evidence of a difference in disability outcomes between HE-DMT-treated and HE-DMT-untreated time was observed. However, among patients ever exposed to HE-DMT, disability worsening was less common while treated with HE-DMT.