• Alessio Signori, Johannes Lorscheider, Sandra Vukusic, Maria Trojano, Pietro Iaffaldano, Jan Hillert, Robert Hyde, Fabio Pellegrini, Melinda Magyari, Nils Koch-Henriksen, Per Soelberg Sørensen, Tim Spelman, Anneke van der Walt, Dana Horakova, Eva Havrdova, Marc Girard, Sara Eichau, Francois Grand'Maison, Oliver Gerlach, Murat Terzi, Serkan Ozakbas, Olga Skibina, Vincent Van Pesch, Maria Jose Sa, Julie Prevost, Raed Alroughani, Pamela A McCombe, Riadh Gouider, Saloua Mrabet, Tamara Castillo-Trivino, Chao Zhu, Koen de Gans, José Luis Sánchez-Menoyo, Bassem Yamout, Samia Khoury, Maria Pia Sormani, Tomas Kalincik, Helmut Butzkueven, and Big MS Data Network.
• Department of Health Sciences, University of Genoa, Genoa, Italy alessio.signori@medicina.unige.it.
• J. Neurol. Neurosurg. Psychiatr. 2023 Jan 1; 94 (1): 233023-30.

BackgroundOver 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.MethodsAll 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.ResultsA 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.ConclusionsContrary 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.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

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