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Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry
Journal article

Effect of late-onset on multiple sclerosis phenotype and outcome: evidence from a multi-national registry

Amira Souissi, Francesco Patti, Tim Spelman, Clara Chisari, Amina Gargouri, Nevin John, Allan G Kermode, Tomas Kalincik, Helmut Butzkueven, Seyed Aidin Sajedi, …
Journal of Neurology, Vol.273(2), 114
2026

Abstract

Multiple Sclerosis Prognosis Aging Progression Immunosenescence
Background Multiple Sclerosis (MS) severity is influenced by several factors. Understanding the impact of age at disease onset may help to better characterize clinical and disease features across age groups. This study aimed to characterize the clinical features and disability outcomes of late-onset MS (LOMS) and very late-onset MS (vLOMS), compared to adult-onset MS (AOMS). Methods We conducted an observational study using data from the MSBase registry and categorized patients based on age at MS onset: AOMS (18–39 years), transition onset (40–49 years), LOMS (50–59 years), and vLOMS (≥ 60 years). Disease progression was assessed using the 24 week confirmed disability progression, EDSS4 and 6 milestones, conversion to secondary progressive MS(SPMS), and the first progression independent of relapse activity (PIRA) event. Cox proportional hazard regression models were used to determine unadjusted hazard ratios(HR), and propensity score inverse probability of treatment weighting(PS-IPTW) balanced covariate distributions. Results Among 81,236 patients, 5.2% had LOMS and 1% had vLOMS. Primary progressive MS was more frequent in LOMS and vLOMS (21.7 and 24%, respectively). Patients with LOMS and vLOMS had a significantly increased risk of 24 week confirmed disability progression (HR:LOMS = 1.39, vLOMS = 1.80), EDSS 4 (HR:LOMS = 2.14, vLOMS = 2.95), EDSS 6 (HR:LOMS = 2.33, vLOMS = 6.33), SPMS (HR:LOMS = 1.62, vLOMS = 2.38), and first PIRA event (HR:LOMS = 2.12, vLOMS = 2.93). Conclusion LOMS and vLOMS exhibited a more progressive disease onset and higher disability milestones compared with AOMS.

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