247 Clinically silent MRI lesions in RRMS: prognostic impact and an emulated trial of disease modifying therapy escalation

a:2:{s:4:"lang";s:2:"en";s:7:"content";s:1770:"<h3>Background</h3> Clinical guidelines for relapsing remitting multiple sclerosis (RRMS) do not recommend disease modifying therapy (DMT) escalation after a single on-treatment clinically silent MRI lesion (CSL). <h3>Methods</h3> From the MSBase international registry, we studied adults with RRMS who had MRI brain scans 6-18 months apart while clinically stable and established on a DMT. Cox models compared outcomes (relapse and 6 month confirmed disability worsening [CDW]) in those with and without CSLs, adjusted for sex, age, calendar year, MS duration, EDSS score, relapses in the prior 2 years, DMT efficacy and country health expenditure. In those with CSLs on platform or moderate-efficacy DMTs, an emulated a target trial compared DMT escalation within 6 months of a silent lesion versus unchanged DMT (unless a post-MRI clinical event occurred). <h3>Results</h3> Among 10,308 people with RRMS, 2-year hazard ratios (HR [95% confidence interval]) comparing CSL with no CSL were 1.78 [1.59–2.00] for relapse and 1.38 [1.18–1.61] for CDW. Associations were similar in people with both single and multiple CSLs, on platform and moderate-efficacy baseline DMTs, and regardless of disease duration. In 2,295 people with CSLs on platform and moderate-efficacy DMTs, DMT escalation (n=288) reduced the median 4-year relapse risk from 38.9% to 17.0% (HR 0.34 [0.23–0.48]). <h3>Conclusions</h3> People with RRMS with single or multiple on-treatment clinically silent MRI lesions have higher subsequent risks of relapse and disability worsening than those without CSLs. DMT escalation mitigates the relapse risk. Contrary to clinical guidelines, DMT escalation should be considered even after a single CSL. cyrus.daruwalla{at}nhs.net ";}

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Publication Details

Published
2025-11-26
DOI
https://doi.org/10.1136/jnnp-2025-abn.247
Primary Topic
Multiple Sclerosis Research Studies
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article
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article

247 Clinically silent MRI lesions in RRMS: prognostic impact and an emulated trial of disease modifying therapy escalation

Multiple Sclerosis Research Studies
article

247 Clinically silent MRI lesions in RRMS: prognostic impact and an emulated trial of disease modifying therapy escalation

article en

Abstract

a:2:{s:4:"lang";s:2:"en";s:7:"content";s:1770:"<h3>Background</h3> Clinical guidelines for relapsing remitting multiple sclerosis (RRMS) do not recommend disease modifying therapy (DMT) escalation after a single on-treatment clinically silent MRI lesion (CSL). <h3>Methods</h3> From the MSBase international registry, we studied adults with RRMS who had MRI brain scans 6-18 months apart while clinically stable and established on a DMT. Cox models compared outcomes (relapse and 6 month confirmed disability worsening [CDW]) in those with and without CSLs, adjusted for sex, age, calendar year, MS duration, EDSS score, relapses in the prior 2 years, DMT efficacy and country health expenditure. In those with CSLs on platform or moderate-efficacy DMTs, an emulated a target trial compared DMT escalation within 6 months of a silent lesion versus unchanged DMT (unless a post-MRI clinical event occurred). <h3>Results</h3> Among 10,308 people with RRMS, 2-year hazard ratios (HR [95% confidence interval]) comparing CSL with no CSL were 1.78 [1.59–2.00] for relapse and 1.38 [1.18–1.61] for CDW. Associations were similar in people with both single and multiple CSLs, on platform and moderate-efficacy baseline DMTs, and regardless of disease duration. In 2,295 people with CSLs on platform and moderate-efficacy DMTs, DMT escalation (n=288) reduced the median 4-year relapse risk from 38.9% to 17.0% (HR 0.34 [0.23–0.48]). <h3>Conclusions</h3> People with RRMS with single or multiple on-treatment clinically silent MRI lesions have higher subsequent risks of relapse and disability worsening than those without CSLs. DMT escalation mitigates the relapse risk. Contrary to clinical guidelines, DMT escalation should be considered even after a single CSL. cyrus.daruwalla{at}nhs.net ";}

University of Foggia (IT), Tunis University (TN), Tallinn University of Technology (EE), St. Michael's Hospital (CA), Cliniques Universitaires Saint-Luc (BE), The Royal Melbourne Hospital (AU), Izmir University (TR), University of Debrecen (HU), Box Hill Hospital (AU), University Hospital Centre Zagreb (HR), University of Antwerp (BE), İzmir University of Economics (TR), The University of Queensland (AU), The University of Melbourne (AU), Queen Mary University of London (GB), Flinders University (AU), University of Zagreb (HR), Charles University (CZ), Masaryk University (CZ), Ondokuz Mayıs University (TR), University of Cambridge (GB), University of L'Aquila (IT), Royal Brisbane and Women's Hospital (AU), John Hunter Hospital (AU), Ghent University Hospital (BE), Frimley Park Hospital (GB), Centre Hospitalier Universitaire de Sherbrooke (CA), The Alfred Hospital (AU), University Hospital of Basel (CH), Royal Hobart Hospital (AU), Westmead Hospital (AU), Amiri Hospital (KW), Hospital de São João (PT), Maastricht University (NL), University of Bristol (GB), Universidad Nacional de Colombia (CO), University of Chieti-Pescara (IT), Bakırköy Psychiatric Hospital (TR), Technology Innovation Institute (AE), St Vincent's Hospital Sydney (AU), Hunter Medical Research Institute (AU), University Hospital Ostrava (CZ), BioCruces Health research Institute (ES), Hospital Universitario Virgen Macarena (ES), Ospedale "Santa Maria delle Croci" di Ravenna (IT), University Hospital in Motol (CZ), Eastern Health (AU), Biogipuzkoa Health Research Institute (ES), East Suffolk and North Essex NHS Foundation Trust (GB), Antwerp University Hospital (BE), American University of Beirut Medical Center (LB), Ospedale Garibaldi (IT), University Hospital Olomouc (CZ), Administração Regional de Saúde de Lisboa e Vale do Tejo (PT), Azienda Ospedaliera S.Giuseppe Moscati (IT), Hospital Clínic de Barcelona (ES), Hospital de Galdakao (ES), Don Carlo Gnocchi Foundation (IT), Monash Health (AU), Istituto delle Scienze Neurologiche di Bologna (IT), Nemocnice České Budějovice (CZ), Policlinico Universitario di Catania (IT), Zuyderland Medisch Centrum (NL), Centre for Disability Prevention and Rehabilitation (CA), University Hospital Hradec Králové (CZ), Mind Australia (AU), Regional Museum in Teplice (CZ), Ingham Institute (AU), Institute of Neuroimmunology of the Slovak Academy of Sciences (SK), Centre intégré de santé et de services sociaux de Chaudière-Appalaches (CA), Farabi Hastanesi (TR), Hospital Universitario Virgen de la Arrixaca (ES), National Hospital for Neurology and Neurosurgery (GB), Istituti di Ricovero e Cura a Carattere Scientifico (IT), University Hospital Kralovske Vinohrady (CZ), Addenbrooke's Hospital (GB), Hospital Universitario Nacional de Colombia (CO), General University Hospital in Prague (CZ), Austin Health (AU), Razi Hospital (IR), South Eastern Health and Social Care Trust (GB), Faculté de médecine de Tunis, University of Florence (IT), University College London (GB), Sultan Qaboos University (OM), University of Macerata (IT), Monash University (AU), Tunis El Manar University (TN), Universidad Católica de Murcia (ES), Palacký University Olomouc (CZ), Université de Montréal (CA), Hasselt University (BE), University of Bologna (IT), UCLouvain (BE)
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