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Introduction <p>Late-onset multiple sclerosis (LOMS), usually defined as symptom onset at age 50&#xa0;years or older, is associated with faster disability accumulation than adult-onset multiple sclerosis (AOMS). Whether this worse prognosis is explained by conventional inflammatory markers remains uncertain.</p> Methods <p>We analysed patients with relapsing–remitting multiple sclerosis from the Ravenna Multiple Sclerosis Registry (RMSR). Patients were classified as AOMS (onset 18–49&#xa0;years) or LOMS (onset ≥ 50&#xa0;years). The primary outcome was recurrent confirmed disability worsening (CDW). Secondary outcomes were progression independent of relapse activity (PIRA) and progression independent of relapse and MRI activity (PIRMA). Associations between onset group and recurrent disability outcomes were assessed using Andersen–Gill models in the unweighted cohort and in an inverse probability weighting (IPTW) pseudo-population. Exploratory complete-case analyses additionally adjusted for baseline MRI and cerebrospinal fluid (CSF) variables.</p> Results <p>A total of 888 patients were included: 759 AOMS and 129 LOMS. In unweighted analyses, LOMS was associated with higher hazards of recurrent CDW, PIRA, and PIRMA. After IPTW, the association with CDW was attenuated and no longer statistically significant (HR 1.16, 95% CI 0.86–1.55), whereas LOMS remained independently associated with PIRA (HR 1.55, 95% CI 1.10–2.18) and, to a lesser extent, PIRMA (HR 1.63, 95% CI 1.10–2.41). In exploratory MRI- and CSF-adjusted models, the association between LOMS and relapse-independent disability accrual remained evident, although attenuation was observed for PIRMA after adjustment for baseline MRI variables.</p> Conclusions <p>LOMS is associated with greater relapse-independent disability accrual, with the most consistent evidence observed for PIRA. Findings for PIRMA were directionally consistent but less robust in exploratory models including baseline MRI variables, supporting a more cautious interpretation.</p>

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Late-onset multiple sclerosis is associated with relapse-independent disability accrual: a propensity score-weighted recurrent-event study

  • 期刊论文

  • 发表日期：

    2026年5月22日

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  • Andrea Surcinelli,
  • Ivan Panzera,
  • Maria Grazia Piscaglia,
  • Sabrina Zagnoli,
  • Emma Rossetto,
  • Luca Mancinelli,
  • Cristiana Ganino,
  • Marco Masullo,
  • Oriana Nanni,
  • Alessandra Lugaresi,
  • Matteo Foschi

摘要

Introduction

Late-onset multiple sclerosis (LOMS), usually defined as symptom onset at age 50 years or older, is associated with faster disability accumulation than adult-onset multiple sclerosis (AOMS). Whether this worse prognosis is explained by conventional inflammatory markers remains uncertain.

Methods

We analysed patients with relapsing–remitting multiple sclerosis from the Ravenna Multiple Sclerosis Registry (RMSR). Patients were classified as AOMS (onset 18–49 years) or LOMS (onset ≥ 50 years). The primary outcome was recurrent confirmed disability worsening (CDW). Secondary outcomes were progression independent of relapse activity (PIRA) and progression independent of relapse and MRI activity (PIRMA). Associations between onset group and recurrent disability outcomes were assessed using Andersen–Gill models in the unweighted cohort and in an inverse probability weighting (IPTW) pseudo-population. Exploratory complete-case analyses additionally adjusted for baseline MRI and cerebrospinal fluid (CSF) variables.

Results

A total of 888 patients were included: 759 AOMS and 129 LOMS. In unweighted analyses, LOMS was associated with higher hazards of recurrent CDW, PIRA, and PIRMA. After IPTW, the association with CDW was attenuated and no longer statistically significant (HR 1.16, 95% CI 0.86–1.55), whereas LOMS remained independently associated with PIRA (HR 1.55, 95% CI 1.10–2.18) and, to a lesser extent, PIRMA (HR 1.63, 95% CI 1.10–2.41). In exploratory MRI- and CSF-adjusted models, the association between LOMS and relapse-independent disability accrual remained evident, although attenuation was observed for PIRMA after adjustment for baseline MRI variables.

Conclusions

LOMS is associated with greater relapse-independent disability accrual, with the most consistent evidence observed for PIRA. Findings for PIRMA were directionally consistent but less robust in exploratory models including baseline MRI variables, supporting a more cautious interpretation.