Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis

Yi Chao Foong; Daniel Merlo; Melissa Gresle; Katherine Buzzard; Dana Horakova; Eva Kubala Havrdova; Tomas Kalincik; Izanne Roos; Suzanne Hodgkinson; Jeannette Lechner-Scott; Alessandra Lugaresi; Bianca Weinstock-Guttman; Serkan Ozakbas; Andrea Surcinelli; Matteo Foschi; Cavit Boz; Samia Joseph Khoury; Bassem Yamout; Guy Laureys; Yolanda Blanco; Olga Skibina; Jens Kuhle; Nevin John; Raed Alroughani; Julie Prevost; Vincent Van Pesch; Valentina Tomassini; Alexandre Prat; Marc Girard; Murat Terzi; Vahid Shaygannejad; Radek Ampapa; Orla Gray; Masoud Etemadifar; Joana Guimarães; Pamela A. Mccombe; Oliver Gerlach; Claudio Solaro; Helmut Butzkueven; Chao Zhu; Anneke Van Der Walt; MSBase Study Group

doi:10.1136/jnnp-2025-336513

Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis

Yi Chao Foong
, Daniel Merlo
, Melissa Gresle
, Katherine Buzzard
, Dana Horakova
, Eva Kubala Havrdova
, Tomas Kalincik
, Izanne Roos
, Suzanne Hodgkinson
, Jeannette Lechner-Scott
, Alessandra Lugaresi
, Bianca Weinstock-Guttman
, Serkan Ozakbas
, Andrea Surcinelli
, Matteo Foschi
, Cavit Boz
, Samia Joseph Khoury
, Bassem Yamout
, Guy Laureys
, Yolanda Blanco

Olga Skibina, Jens Kuhle, Nevin John, Raed Alroughani, Julie Prevost, Vincent Van Pesch, Valentina Tomassini, Alexandre Prat, Marc Girard, Murat Terzi, Vahid Shaygannejad, Radek Ampapa, Orla Gray, Masoud Etemadifar, Joana Guimarães, Pamela A. Mccombe, Oliver Gerlach, Claudio Solaro, Helmut Butzkueven, Chao Zhu, Anneke Van Der Walt, MSBase Study Group

Neurology

University of Tasmania
Royal Hobart Hospital
Monash University
University of Melbourne
Melbourne Brain Centre
Box Hill Hospital
Charles University
Royal Melbourne Hospital
Liverpool Hospital
University of Newcastle
IRCCS Istituto delle Scienze Neurologiche di Bologna
University of Bologna
Dokuz Eylul University
Ospedale S. Maria delle Croci
Karadeniz Technical University
American University of Beirut
Ghent University
Hospital Clinic de Barcelona
The Alfred
University of Basel
School of Clinical Sciences at Monash Health
Al-Amiri Hospital
Centre integre de sante et de services sociaux des Laurentides point de service de Saint-Jerome
Université catholique de Louvain
Gabriele d'Annunzio University
Cardiff & Vale University Health Board
University of Montreal
Centre Hospitalier de L'Universite de Montreal
Ondokuz Mayis University
Isfahan University of Medical Sciences
Nemocnice Jihlava
Southern Health and Social Care Trust
Isfahan Multiple Sclerosis Society
Centro Hospitalar Universitário de São João
University of Queensland
Zuyderland
ASL 3 Genovese
Alfred Health

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

Abstract

Introduction Late-onset multiple sclerosis (LOMS) now comprises over 10% of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate-high-efficacy versus low-efficacy DMTs in LOMS. Methods Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Results Of 1032 participants, 472 received moderate-high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate-high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95% CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95% CI 0.47 to 0.91, p=0.01) in favour of moderate-high-efficacy DMTs. Among 856 participants with adequate follow-up, 37% experienced CDP over a median of 4.43 years, with most events (83.6%) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate-high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA. Conclusion Moderate-high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate-high-efficacy DMTs in LOMS.

Original language	English
Article number	jnnp-2025-336513
Journal	Journal of Neurology, Neurosurgery and Psychiatry
DOIs	https://doi.org/10.1136/jnnp-2025-336513
State	Accepted/In press - 2025

Keywords

DEMYELINATING DISEASES
GERIATRICS
MULTIPLE SCLEROSIS
STATISTICS

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10.1136/jnnp-2025-336513

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Foong, Y. C., Merlo, D., Gresle, M., Buzzard, K., Horakova, D., Havrdova, E. K., Kalincik, T., Roos, I., Hodgkinson, S., Lechner-Scott, J., Lugaresi, A., Weinstock-Guttman, B., Ozakbas, S., Surcinelli, A., Foschi, M., Boz, C., Khoury, S. J., Yamout, B., Laureys, G., ... Study Group, MSB. (Accepted/In press). Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis. Journal of Neurology, Neurosurgery and Psychiatry, Article jnnp-2025-336513. https://doi.org/10.1136/jnnp-2025-336513

@article{7b10e06de5a24314855d84e653de8a49,

title = "Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis",

abstract = "Introduction Late-onset multiple sclerosis (LOMS) now comprises over 10\% of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate-high-efficacy versus low-efficacy DMTs in LOMS. Methods Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Results Of 1032 participants, 472 received moderate-high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate-high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95\% CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95\% CI 0.47 to 0.91, p=0.01) in favour of moderate-high-efficacy DMTs. Among 856 participants with adequate follow-up, 37\% experienced CDP over a median of 4.43 years, with most events (83.6\%) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate-high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA. Conclusion Moderate-high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate-high-efficacy DMTs in LOMS.",

keywords = "DEMYELINATING DISEASES, GERIATRICS, MULTIPLE SCLEROSIS, STATISTICS",

author = "Foong, \{Yi Chao\} and Daniel Merlo and Melissa Gresle and Katherine Buzzard and Dana Horakova and Havrdova, \{Eva Kubala\} and Tomas Kalincik and Izanne Roos and Suzanne Hodgkinson and Jeannette Lechner-Scott and Alessandra Lugaresi and Bianca Weinstock-Guttman and Serkan Ozakbas and Andrea Surcinelli and Matteo Foschi and Cavit Boz and Khoury, \{Samia Joseph\} and Bassem Yamout and Guy Laureys and Yolanda Blanco and Olga Skibina and Jens Kuhle and Nevin John and Raed Alroughani and Julie Prevost and \{Van Pesch\}, Vincent and Valentina Tomassini and Alexandre Prat and Marc Girard and Murat Terzi and Vahid Shaygannejad and Radek Ampapa and Orla Gray and Masoud Etemadifar and Joana Guimar{\~a}es and Mccombe, \{Pamela A.\} and Oliver Gerlach and Claudio Solaro and Helmut Butzkueven and Chao Zhu and \{Van Der Walt\}, Anneke and \{Study Group\}, MSBase",

note = "Publisher Copyright: {\textcopyright} 2025 Author(s) (or their employer(s)).",

year = "2025",

doi = "10.1136/jnnp-2025-336513",

language = "English",

journal = "Journal of Neurology, Neurosurgery and Psychiatry",

issn = "0022-3050",

publisher = "BMJ Publishing Group",

}

Foong, YC, Merlo, D, Gresle, M, Buzzard, K, Horakova, D, Havrdova, EK, Kalincik, T, Roos, I, Hodgkinson, S, Lechner-Scott, J, Lugaresi, A, Weinstock-Guttman, B, Ozakbas, S, Surcinelli, A, Foschi, M, Boz, C, Khoury, SJ, Yamout, B, Laureys, G, Blanco, Y, Skibina, O, Kuhle, J, John, N, Alroughani, R, Prevost, J, Van Pesch, V, Tomassini, V, Prat, A, Girard, M, Terzi, M, Shaygannejad, V, Ampapa, R, Gray, O, Etemadifar, M, Guimarães, J, Mccombe, PA, Gerlach, O, Solaro, C, Butzkueven, H, Zhu, C, Van Der Walt, A & Study Group, MSB 2025, 'Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis', Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2025-336513

TY - JOUR

T1 - Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis

AU - Foong, Yi Chao

AU - Merlo, Daniel

AU - Gresle, Melissa

AU - Buzzard, Katherine

AU - Horakova, Dana

AU - Havrdova, Eva Kubala

AU - Kalincik, Tomas

AU - Roos, Izanne

AU - Hodgkinson, Suzanne

AU - Lechner-Scott, Jeannette

AU - Lugaresi, Alessandra

AU - Weinstock-Guttman, Bianca

AU - Ozakbas, Serkan

AU - Surcinelli, Andrea

AU - Foschi, Matteo

AU - Boz, Cavit

AU - Khoury, Samia Joseph

AU - Yamout, Bassem

AU - Laureys, Guy

AU - Blanco, Yolanda

AU - Skibina, Olga

AU - Kuhle, Jens

AU - John, Nevin

AU - Alroughani, Raed

AU - Prevost, Julie

AU - Van Pesch, Vincent

AU - Tomassini, Valentina

AU - Prat, Alexandre

AU - Girard, Marc

AU - Terzi, Murat

AU - Shaygannejad, Vahid

AU - Ampapa, Radek

AU - Gray, Orla

AU - Etemadifar, Masoud

AU - Guimarães, Joana

AU - Mccombe, Pamela A.

AU - Gerlach, Oliver

AU - Solaro, Claudio

AU - Butzkueven, Helmut

AU - Zhu, Chao

AU - Van Der Walt, Anneke

AU - Study Group, MSBase

PY - 2025

Y1 - 2025

N2 - Introduction Late-onset multiple sclerosis (LOMS) now comprises over 10% of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate-high-efficacy versus low-efficacy DMTs in LOMS. Methods Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Results Of 1032 participants, 472 received moderate-high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate-high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95% CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95% CI 0.47 to 0.91, p=0.01) in favour of moderate-high-efficacy DMTs. Among 856 participants with adequate follow-up, 37% experienced CDP over a median of 4.43 years, with most events (83.6%) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate-high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA. Conclusion Moderate-high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate-high-efficacy DMTs in LOMS.

AB - Introduction Late-onset multiple sclerosis (LOMS) now comprises over 10% of MS diagnoses in contemporary cohorts. The effectiveness of disease-modifying therapies (DMTs) in LOMS is unclear. We aimed to establish the comparative effectiveness of moderate-high-efficacy versus low-efficacy DMTs in LOMS. Methods Using data from the MSBase registry, this multicentre cohort study included people with MS with symptom onset after age 50. Covariates were balanced using inverse-probability-treatment-weighting (IPTW). Primary outcomes were time to first relapse and annualised relapse rate (ARR). Secondary outcomes were 6-month confirmed disability progression (CDP), confirmed disability improvement (CDI), relapse-associated worsening (RAW) and progression independent of relapse activity (PIRA). Results Of 1032 participants, 472 received moderate-high-efficacy DMTs and 560 received low-efficacy DMTs. IPTW-weighted ARR was 0.06 for moderate-high-efficacy and 0.09 for low-efficacy DMTs, corresponding to an ARR ratio of 0.68 (95% CI 0.50 to 0.93, p=0.01). HR for time to first relapse was 0.66 (95% CI 0.47 to 0.91, p=0.01) in favour of moderate-high-efficacy DMTs. Among 856 participants with adequate follow-up, 37% experienced CDP over a median of 4.43 years, with most events (83.6%) attributable to PIRA. The HR for time to CDP was 0.78 (p=0.08) and RAW was 0.69 (p=0.31) in favour of moderate-high-efficacy DMTs, though neither reached statistical significance. There was no difference in CDI or PIRA. Conclusion Moderate-high-efficacy DMTs reduced relapse risk in LOMS. Relapse activity was low. CDP was common and driven by PIRA. Although the CDP and RAW results did not reach statistical significance, the overall findings support the initial use of moderate-high-efficacy DMTs in LOMS.

KW - DEMYELINATING DISEASES

KW - GERIATRICS

KW - MULTIPLE SCLEROSIS

KW - STATISTICS

UR - https://www.scopus.com/pages/publications/105023643089

U2 - 10.1136/jnnp-2025-336513

DO - 10.1136/jnnp-2025-336513

M3 - Article

C2 - 41161724

AN - SCOPUS:105023643089

SN - 0022-3050

JO - Journal of Neurology, Neurosurgery and Psychiatry

JF - Journal of Neurology, Neurosurgery and Psychiatry

M1 - jnnp-2025-336513

ER -

Moderate-high efficacy disease-modifying therapies reduce relapse risk in late-onset multiple sclerosis

Abstract

Keywords

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