BACKGROUND: Effectiveness of disease-modifying treatment (DMT) in people affected by primary progressive multiple sclerosis (PPMS) is limited. Whether specific subgroups may benefit more from DMT in a real-world setting remains unclear. Our aim was to investigate the potential effect of DMT on disability worsening among patients with PPMS stratified by different disability trajectories. METHODS: Within the framework of the Big MS Data network, we merged data from the Observatoire Français de la Sclérose en Plaques, the Swedish and Italian MS registries, and MSBase. We identified patients with PPMS that started DMT or were never treated during the observed period. Subpopulations with comparable baseline characteristics were selected by propensity score matching. Disability outcomes were analysed in time-to-recurrent event analyses, which were repeated in subclasses with different disability trajectories determined by latent class mixed models. RESULTS: Of the 3243 included patients, we matched 739 treated and 1330 untreated patients with a median follow-up of 3 years after pairwise censoring. No difference in the risk of confirmed disability worsening (CDW) was observed between the groups in the fully matched dataset (HR 1.11, 95% CI 0.97 to 1.23, p=0.127). However, we found a lower risk for CDW among the class of treated patients with an aggressive disability trajectory (n=360, HR 0.68, 95% CI 0.50 to 0.92, p=0.014). CONCLUSIONS: In line with previous studies, our data suggest that DMT does not ameliorate disability worsening in PPMS, in general. However, we observed a beneficial effect of DMT on disability worsening in patients with aggressive predicted disability trajectories.

Academic MS Center Zuyd Department of Neurology Zuyderland Medical Center Sittard Geleen Netherlands

Amiri Hospital Kuwait City Kuwait

Centre Hospitalier Universitaire de Rennes Rennes France

Centre Integre de Sante et de Services Sociaux des Laurentides Saint Jerome Quebec Canada

CHU de Montpellier MS Unit University of Montpellier Montpellier France

CHU Lille CRCSEP Lille Université de Lille Lille France

Clinical Neuroscience Karolinska Institute Stockholm Sweden

Clinical Outcomes Research Unit Department of Medicine University of Melbourne Melbourne Victoria Australia

Department of Clinical Epidemiology Aarhus University Hospital Aarhus Denmark

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Clinical Research University Hospital Basel Basel Switzerland

Department of Health Sciences Section of Biostatistics University of Genoa Genova Italy

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

Department of Neurology and Clinical Investigation Center CHU de Strasbourg and University of Strasbourg Strasbourg France

Department of Neurology Centre Hospitalier Universitaire de Toulouse Toulouse France

Department of Neurology Hôpital Saint Vincent de Paul Lille France

Department of Neurology Nancy University Hospital Université de Lorraine Nancy France

Department of Neurology Neuroimunology Centre The Royal Melbourne Hospital Parkville Victoria Australia

Department of Neurology The Alfred Hospital Melbourne Victoria Australia

Department of Neurology The Danish Multiple Sclerosis Registry Copenhagen University Hospital Rigshospitalet Glostrup Glostrup Denmark

Department of Neurology University Hospital Basel Basel Switzerland

Department of Neuroscience School of Translational Medicine Monash University Melbourne Victoria Australia

Department of Neurosciences Box Hill Hospital Box Hill Victoria Australia

Department of Translational Biomedicine and Neurosciences DiBraiN University of Bari Aldo Moro Bari Italy

Eastern Health Clinical School Monash University Melbourne Victoria Australia

Eugène Devic EDMUS Foundation against multiple sclerosis Lyon France

Hôpital Notre Dame CHUM and Universite de Montreal Montreal Quebec Canada

Hospital Universitario Virgen Macarena Sevilla Spain

Hotel Dieu de Levis Levis Quebec Canada

Hunter Medical Research Institute University of Newcastle Newcastle New South Wales Australia

Hunter New England Health John Hunter Hospital Newcastle New South Wales Australia

Independent Healthcare and Real World Evidence Consultant Zug Switzerland

MSBase Foundation Melbourne Victoria Australia

Neurocentre Magendie Université de Bordeaux Bordeaux France

Neurology AP HP Hôpital de la Pitié Salpêtrière Paris France

Neurology Galdakao Hospital Spain Spain

Neurosciences Hospital Universitari Germans Trias i Pujol Barcelona Spain

Observatoire Français de la Sclérose en Plaques Centre de Recherche en Neurosciences de Lyon Lyon France

Research Center for Clinical Neuroimmunology and Neuroscience Basel University of Basel Basel Switzerland

School for Mental Health and Neuroscience Department of Neurology Maastricht University Medical Center Maastricht Netherlands

Service de Neurologie CHU de Bordeaux Bordeaux France

Service de Neurologie sclérose en plaques pathologies de la myéline et neuro inflammation Hospices Civils de Lyon Lyon France

South Eastern HSC Trust Belfast UK

Université de Lyon Lyon France

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