BACKGROUND: Over the decades, several natural history studies on patients with primary (PPMS) or secondary progressive multiple sclerosis (SPMS) were reported from international registries. In PPMS, a consistent heterogeneity on long-term disability trajectories was demonstrated. The aim of this study was to identify subgroups of patients with SPMS with similar longitudinal trajectories of disability over time. METHODS: All patients with MS collected within Big MS registries who received an SPMS diagnosis from physicians (cohort 1) or satisfied the Lorscheider criteria (cohort 2) were considered. Longitudinal Expanded Disability Status Scale (EDSS) scores were modelled by a latent class growth analysis (LCGA), using a non-linear function of time from the first EDSS visit in the range 3-4. RESULTS: A total of 3613 patients with SPMS were included in the cohort 1. LCGA detected three different subgroups of patients with a mild (n=1297; 35.9%), a moderate (n=1936; 53.6%) and a severe (n=380; 10.5%) disability trajectory. Median time to EDSS 6 was 12.1, 5.0 and 1.7 years, for the three groups, respectively; the probability to reach EDSS 6 at 8 years was 14.4%, 78.4% and 98.3%, respectively. Similar results were found among 7613 patients satisfying the Lorscheider criteria. CONCLUSIONS: Contrary to previous interpretations, patients with SPMS progress at greatly different rates. Our identification of distinct trajectories can guide better patient selection in future phase 3 SPMS clinical trials. Additionally, distinct trajectories could reflect heterogeneous pathological mechanisms of progression.

Amiri Hospital Kuwait City Kuwait

Biogen International Zurich Switzerland

Centre integre de sante et de services sociaux des Laurentides point de service de Saint Jerome Saint Jerome Quebec Canada

CHUM and Universite de Montreal Montreal Quebec Canada

Clinical Neuroscience Karolinska Institute Stockholm Sweden

CORe Department of Medicine University of Melbourne Melbourne Victoria Australia

Department of Basic Medical Sciences Neurosciences and Sense Organs University of Bari Aldo Moro Bari Italy

Department of Clinical Epidemiology Aarhus University Hospital Aarhus Denmark

Department of Health Sciences University of Genoa Genoa Italy

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

Department of Neurology Box Hill Hospital Melbourne Victoria Australia

Department of Neurology Danish Multiple Sclerosis Center Rigshospitalet Copenhagen Denmark

Department of Neurology Razi Hospital Manouba Tunisia

Department of Neurology Razi University Hospital Manouba Tunisia

Department of Neurology Royal Melbourne Hospital Melbourne Victoria Australia

Department of Neurology Zuyderland Medical Center Sittard Geleen The Netherlands

Department of Neuroscience Monash University Central Clinical School Melbourne Victoria Australia

Dokuz Eylul University İzmir Turkey

Faculty of Health Sciences University Fernando Pessoa Porto Portugal

Faculty of Medicine of Tunis University of Tunis El Manar Tunis Tunisia

Groene Hart Ziekenhuis Gouda The Netherlands

Managing Director MSBase Foundation Melbourne Victoria Australia

Monash University Central Clinical School Melbourne Victoria Australia

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

Neuro Rive Sud Quebec Quebec Canada

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

Neurology Box Hill Hospital Melbourne Victoria Australia

Neurology Centro Hospitalar de São João Porto Portugal

Neurology Cliniques Universitaires Saint Luc Brussels Belgium

Neurology Donostia University Hospital San Sebastian Spain

Neurology Galdakao Hospital Vizcaya Spain

Neurology Hospital Universitario Virgen Macarena Sevilla Spain

Neuroscience Centre Clinical School Monash University Victoria Australia

Ondokuz Mayis Üniversitesi Samsun Turkey

School for Mental Health and Neuroscience Maastricht University Maastricht The Netherlands

Service de Neurologie A Hopital Neurologique Hospices Civils de Lyon Lyon Bron France

UQCCR The University of Queensland Brisbane Queensland Australia

Citace poskytuje Crossref.org

Big Multiple Sclerosis Data network: an international registry research network

Zobrazit více v PubMed

ANZCTR
ACTRN12605000455662

ClinicalTrials.gov
NCT02889965