Journal article
Causal effects of multiple sclerosis therapies in left-truncated registry data
Multiple sclerosis, Vol.32(10), pp.1052-1068
2026
PMID: 42479470
Abstract
Background
Left-truncation is an unrecorded interval between multiple sclerosis (MS) onset and initial data in observational studies. This delay may bias estimates of disease-modifying therapy (DMT) effectiveness, especially when determined by patient or disease characteristics.
Objectives
To examine whether causal effect estimates of DMTs over the full disease course can be reliably derived from left-truncated registry data.
Methods
We analysed data from MSBase (144 centres, 41 countries) to assess the impact of left-truncation on causal treatment effect estimates. Cox marginal structural models (MSMs) estimated hazard ratios (HRs) for relapses, disability worsening and improvement, considering left-truncation at random and not-at-random. Fixed-time truncation and multivariable adjustment were applied to remediate bias.
Results
The study included 5588 patients tracked from true MS onset. The null model, without left-truncation, estimated the DMT effect on relapse risk (HR = 0.64; 95% confidence interval (CI) = 0.54–0.77). Left-truncation inflated this estimate. Shorter random truncation (1 year) produced greater bias (HR = 0.34), decreasing with longer durations (3-year HR = 0.48). Truncation not-at-random biased relapse estimates (HR = 0.37). Disability outcomes were less sensitive.
Conclusion
MSMs can reliably estimate DMT effectiveness in left-truncated MS registry data, although accuracy depends on truncation mechanism and duration. Both random and not-at-random truncation impact relapse estimates. Disability outcomes appear less sensitive. Fixed-time truncation and covariate adjustment mitigated bias.
Details
- Title
- Causal effects of multiple sclerosis therapies in left-truncated registry data
- Authors/Creators
- Dagmawi Chilot HaileIbrahima Diouf - Australian e-Health Research CentreSerkan Ozakbas - Izmir UniversityDana Horakova - Charles UniversityEva Kubala Havrdova - Charles UniversityFrancesco Patti - University of CataniaSara Eichau - Instituto de Biomedicina de SevillaRaed Alroughani - Amiri HospitalAlessandra Lugaresi - Istituto delle Scienze Neurologiche di BolognaValentina Tomassini - University of Chieti-PescaraAlexandre Prat - Université de MontréalMarc Girard - Université de MontréalMurat Terzi - Ondokuz Mayıs UniversityBassem Yamout - Harley-Davidson (United States)Samia J Khoury - American University of Beirut Medical CenterPierre Grammond - Centre intégré de santé et de services sociaux de Chaudière-AppalachesYolanda Blanco - Hospital Clínic de BarcelonaVahid Shaygannejad - Isfahan University of Medical SciencesMatteo Foschi - Ospedale "Santa Maria delle Croci" di RavennaAndrea Surcinelli - Ospedale "Santa Maria delle Croci" di RavennaStefano Neri - Ospedale "Santa Maria delle Croci" di RavennaBianca Weinstock-Guttman - Jacobs InstituteJulie Prevost - Cegep de Saint JeromeMaria Pia Amato - University of FlorenceMichael Barnett - Mind AustraliaOliver Gerlach - Zuyderland Medisch CentrumNevin John - Monash HealthAllan G Kermode - Murdoch UniversityMarzena Fabis-Pedrini - Murdoch UniversityWilliam M Carroll - Murdoch UniversityAnneke van der Walt - Monash UniversityHelmut Butzkueven - Monash UniversityVincent van Pesch - Cliniques Universitaires Saint-LucAysun Soysal - Bakırköy Psychiatric HospitalRiadh Gouider - Tunis El Manar UniversitySaloua Mrabet - Tunis El Manar UniversityDaniele Spitaleri - Azienda Ospedaliera S.Giuseppe MoscatiElisabetta Cartechini - University of MacerataDavide Maimone - Ospedale CannizzaroRadek Ampapa - Hospital JihlavaGuy Laureys - Ghent University HospitalCristina Ramo-Tello - Hospital Universitari Germans Trias i PujolMaria Di Gregorio - Ospedali Riuniti San Giovanni di Dio e Ruggi d'AragonaEmmanuelle Lapointe - Centre Hospitalier Universitaire de SherbrookeMark Slee - Flinders UniversityRana Karabudak - Yeditepe University HospitalJustin Garber - Westmead HospitalAyse Altintas - Koç UniversitySuzanne Hodgkinson - Ingham InstituteJose Luis Sanchez-Menoyo - Hospital de GaldakaoTamara Castillo-Triviño - Biogipuzkoa Health Research InstituteMario Habek - University Hospital Centre ZagrebAbdullah Al-Asmi - Sultan Qaboos UniversityTalal Al-Harbi - King Fahad Specialist HospitalTunde Csepany - University of DebrecenSimón Cárdenas-Robledo - Hospital Universitario Nacional de ColombiaBruce Taylor - Royal Hobart HospitalYi Chao Foong - Royal Hobart HospitalBarbara Willekens - University of AntwerpNevin Shalaby - Cairo UniversityFraser Moore - Jewish General HospitalChris McGuigan - St. Vincent's University HospitalSeyed Mohammad Baghbanian - Mazandaran University of Medical SciencesJennifer Massey - St Vincent's Hospital SydneyTodd A Hardy - Concord Repatriation General HospitalSudarshini Ramanathan - Anzac Research InstituteKatrin Gross-Paju - East Tallinn Central HospitalOrla Gray - South Eastern Health and Social Care TrustDanny Decoo - Universitair Ziekenhuis BrusselCameron Shaw - Barwon HealthMihaela Simu - Camera de Comerț Industrie și Agricultură TimișoaraCsilla Rozsa - Jahn Ferenc Dél-Pesti Kórház és RendelőintézetElizabeth A Stuart - Johns Hopkins UniversitySifat Sharmin - The Royal Melbourne HospitalIzanne Roos - The Royal Melbourne HospitalTomas Kalincik - The Royal Melbourne Hospital
- Publication Details
- Multiple sclerosis, Vol.32(10), pp.1052-1068
- Identifiers
- 991005912894107891
- Copyright
- © The Author(s), 2026
- Murdoch Affiliation
- Institute for Immunology and Infectious Diseases
- Language
- English
- Resource Type
- Journal article
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