BACKGROUND AND PURPOSE: This study assessed the effect of patient characteristics on the response to disease-modifying therapy (DMT) in multiple sclerosis (MS). METHODS: We extracted data from 61,810 patients from 135 centers across 35 countries from the MSBase registry. The selection criteria were: clinically isolated syndrome or definite MS, follow-up ≥ 1 year, and Expanded Disability Status Scale (EDSS) score ≥ 3, with ≥1 score recorded per year. Marginal structural models with interaction terms were used to compare the hazards of 12-month confirmed worsening and improvement of disability, and the incidence of relapses between treated and untreated patients stratified by their characteristics. RESULTS: Among 24,344 patients with relapsing MS, those on DMTs experienced 48% reduction in relapse incidence (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.45-0.60), 46% lower risk of disability worsening (HR = 0.54, 95% CI = 0.41-0.71), and 32% greater chance of disability improvement (HR = 1.32, 95% CI = 1.09-1.59). The effect of DMTs on EDSS worsening and improvement and the risk of relapses was attenuated with more severe disability. The magnitude of the effect of DMT on suppressing relapses declined with higher prior relapse rate and prior cerebral magnetic resonance imaging activity. We did not find any evidence for the effect of age on the effectiveness of DMT. After inclusion of 1985 participants with progressive MS, the effect of DMT on disability mostly depended on MS phenotype, whereas its effect on relapses was driven mainly by prior relapse activity. CONCLUSIONS: DMT is generally most effective among patients with lower disability and in relapsing MS phenotypes. There is no evidence of attenuation of the effect of DMT with age.

Aarhus University Hospital Aarhus Denmark

Austin Health Melbourne Victoria Australia

Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino Avellino Italy

Bakirkoy Education and Research Hospital for Psychiatric and Neurological Diseases Istanbul Turkey

Brain and Mind Centre Sydney New South Wales Australia

Center of Neuroimmunology Service of Neurology Hospital Clinic of Barcelona Barcelona Spain

Central Clinical School Monash University Melbourne Victoria Australia

CHUM Mississippi Center and University of Montreal Montreal Quebec Canada

CISSS Chaudière Appalache Levis Sainte Marie Quebec Canada

Cliniques Universitaires Saint Luc Louvain Brussels Belgium

CSSS Saint Jerome Saint Jerome Quebec Canada

Department of Medical and Surgical Sciences and Advanced Technologies GF Ingrassia Catania Italy

Department of Medicine and Surgery University of Parma Parma Italy

Department of Medicine CORe University of Melbourne Melbourne Victoria Australia

Department of Medicine Sultan Qaboos University Hospital Seeb Oman

Department of Neurology Alfred Hospital Melbourne Victoria Australia

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Neurology ASL3 Genovese Genoa Italy

Department of Neurology Centro Hospitalar Universitário de São João Porto Portugal

Department of Neurology Faculty of Medicine University of Debrecen Debrecen Hungary

Department of Neurology Neuroimmunology Centre Royal Melbourne Hospital Melbourne Victoria Australia

Department of Neurology Razi Hospital Manouba Tunisia

Department of Neurology School of Medicine Koc University Istanbul Turkey

Department of Neuroscience Azienda Ospedaliera Universitaria Modena Italy

Department of Neuroscience Imaging and Clinical Sciences D'Annunzio University Chieti Italy

Department of Rehabilitation ML Novarese Hospital Moncrivello Genoa Italy

Departments of Medicine and Clinical Research Neurologic Clinic and Policlinic University Hospital and University of Basel Basel Switzerland

Dipartimento di Scienze Biomediche e Neuromotorie Università di Bologna Bologna Italy

Division of Neurology Department of Medicine Amiri Hospital Sharq Kuwait

Dokuz Eylul University Konak Izmir Turkey

Flinders University Adelaide South Australia Australia

Garibaldi Hospital Catania Italy

Groene Hart Ziekenhuis Gouda the Netherlands

Hacettepe University Ankara Turkey

Haydarpasa Numune Training and Research Hospital Istanbul Turkey

Hospital de Galdakao Usansolo Galdakao Spain

Hospital Fernandez Buenos Aires Argentina

Hospital General Universitario de Alicante Alicante Spain

Hospital Italiano Buenos Aires Argentina

Hospital Universitario Virgen Macarena Seville Spain

Instituto de Investigacion Sanitaria Biodonostia Hospital Universitario Donostia San Sebastian Spain

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran Mexico City Mexico

IRCCS Istituto delle Scienze Neurologiche di Bologna Bologna Italy

IRCCS Mondino Foundation Pavia Italy

Isfahan University of Medical Sciences Isfahan Iran

Jewish General Hospital Montreal Quebec Canada

Koc University Research Center for Translational Medicine Istanbul Turkey

KTU Medical Faculty Farabi Hospital Trabzon Turkey

Liverpool Hospital Sydney New South Wales Australia

Medical Center Leeuwarden Leeuwarden the Netherlands

Monash Medical Centre Melbourne Victoria Australia

Nehme and Therese Tohme Multiple Sclerosis Center American University of Beirut Medical Center Beirut Lebanon

Nemocnice Jihlava Jihlava Czech Republic

Neuro Rive Sud Quebec City Quebec Canada

Neurology Department King Fahad Specialist Hospital Dammam Dammam Saudi Arabia

Neurology Kasr Al Ainy MS Research Unit Cairo Egypt

Ospedali Riuniti di Salerno Salerno Italy

Postgraduate Institute of Medical Education and Research Chandigarh India

Rehabilitation and MS Center Overpelt and Hasselt University Hasselt Belgium

Royal Victoria Hospital Belfast UK

School of Medicine and Public Health University of Newcastle Newcastle New South Wales Australia

School of Medicine Ondokuz Mayis University Samsun Turkey

South East Trust Belfast UK

St Vincent's University Hospital Dublin Ireland

Trias and Pujol Brothers University Hospital Badalona Spain

Universidade Metropolitana de Santos Santos Brazil

University Hospital Geelong Geelong Victoria Australia

University Hospital Ghent Ghent Belgium

University Hospital Reina Sofia Cordoba Spain

University of Queensland Brisbane Queensland Australia

UOC Neurologia Azienda Sanitaria Unica Regionale Marche AV3 Macerata Italy

Waikato Hospital Hamilton New Zealand

Westmead Hospital Sydney New South Wales Australia

Zuyderland Medical Center Sittard Geleen the Netherlands

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