• Sam Harding-Forrester, Izanne Roos, Ai-Lan Nguyen, Charles B Malpas, Ibrahima Diouf, Nahid Moradi, Sifat Sharmin, Guillermo Izquierdo, Sara Eichau, Francesco Patti, Dana Horakova, Eva Kubala Havrdova, Alexandre Prat, Marc Girard, Pierre Duquette, Francois Grand'Maison, Marco Onofrj, Alessandra Lugaresi, Pierre Grammond, Serkan Ozakbas, Maria Pia Amato, Oliver Gerlach, Patrizia Sola, Diana Ferraro, Katherine Buzzard, Olga Skibina, Jeannette Lechner-Scott, Raed Alroughani, Cavit Boz, Vincent Van Pesch, Elisabetta Cartechini, Murat Terzi, Davide Maimone, Cristina Ramo-Tello, Bassem Yamout, Samia Joseph Khoury, Daniele La Spitaleri, Maria Jose Sa, Yolanda Blanco, Franco Granella, Mark Slee, Ernest Butler, Youssef Sidhom, Riadh Gouider, Roberto Bergamaschi, Rana Karabudak, Radek Ampapa, José Luis Sánchez-Menoyo, Julie Prevost, Tamara Castillo-Trivino, Pamela A McCombe, Richard Macdonell, Guy Laureys, Liesbeth Van Hijfte, Jiwon Oh, Ayse Altintas, Koen de Gans, Recai Turkoglu, Anneke van der Walt, Helmut Butzkueven, Steve Vucic, Michael Barnett, Edgardo Cristiano, Suzanne Hodgkinson, Gerardo Iuliano, Ludwig Kappos, Jens Kuhle, Vahid Shaygannejad, Aysun Soysal, Bianca Weinstock-Guttman, Bart Van Wijmeersch, Tomas Kalincik, and MSBase investigators.
• CORe, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia.
• J. Neurol. Neurosurg. Psychiatr. 2023 Sep 1; 94 (9): 707717707-717.

BackgroundSome studies comparing primary and secondary progressive multiple sclerosis (PPMS, SPMS) report similar ages at onset of the progressive phase and similar rates of subsequent disability accrual. Others report later onset and/or faster accrual in SPMS. Comparisons have been complicated by regional cohort effects, phenotypic differences in sex ratio and management and variable diagnostic criteria for SPMS.MethodsWe compared disability accrual in PPMS and operationally diagnosed SPMS in the international, clinic-based MSBase cohort. Inclusion required PPMS or SPMS with onset at age ≥18 years since 1995. We estimated Andersen-Gill hazard ratios for disability accrual on the Expanded Disability Status Scale (EDSS), adjusted for sex, age, baseline disability, EDSS score frequency and drug therapies, with centre and patient as random effects. We also estimated ages at onset of the progressive phase (Kaplan-Meier) and at EDSS milestones (Turnbull). Analyses were replicated with physician-diagnosed SPMS.ResultsIncluded patients comprised 1872 with PPMS (47% men; 50% with activity) and 2575 with SPMS (32% men; 40% with activity). Relative to PPMS, SPMS had older age at onset of the progressive phase (median 46.7 years (95% CI 46.2-47.3) vs 43.9 (43.3-44.4); p<0.001), greater baseline disability, slower disability accrual (HR 0.86 (0.78-0.94); p<0.001) and similar age at wheelchair dependence.ConclusionsWe demonstrate later onset of the progressive phase and slower disability accrual in SPMS versus PPMS. This may balance greater baseline disability in SPMS, yielding convergent disability trajectories across phenotypes. The different rates of disability accrual should be considered before amalgamating PPMS and SPMS in clinical trials.© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

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