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Tomas Kalincik, Vino Vivek, Vilija Jokubaitis, Jeannette Lechner-Scott, Maria Trojano, Guillermo Izquierdo, Alessandra Lugaresi, Francois Grand’Maison, Raymond Hupperts, Celia Oreja-Guevara, Roberto Bergamaschi, Gerardo Iuliano, Raed Alroughani, Vincent Van Pesch, Maria Pia Amato, Mark Slee, Freek Verheul, Ricardo Fernandez-Bolanos, Marcela Fiol, Daniele La Spitaleri, Edgardo Cristiano, Orla Gray, Jose Antonio Cabrera-Gomez, Vahid Shaygannejad, Joseph Herbert, Steve Vucic, Merilee Needham, Tatjana Petkovska-Boskova, Carmen-Adella Sirbu, Pierre Duquette, Marc Girard, Pierre Grammond, Cavit Boz, Giorgio Giuliani, Maria Edite Rio, Michael Barnett, Shlomo Flechter, Fraser Moore, Bhim Singhal, Elizabeth Alejandra Bacile, Maria Laura Saladino, Cameron Shaw, Eli Skromne, Dieter Poehlau, Norbert Vella, Timothy Spelman, Danny Liew, Trevor J. Kilpatrick, Helmut Butzkueven, on behalf of the MSBase Study Group, Sex as a determinant of relapse incidence and progressive course of multiple sclerosis, Brain, Volume 136, Issue 12, December 2013, Pages 3609–3617, https://doi.org/10.1093/brain/awt281
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Abstract
The aim of this work was to evaluate sex differences in the incidence of multiple sclerosis relapses; assess the relationship between sex and primary progressive disease course; and compare effects of age and disease duration on relapse incidence. Annualized relapse rates were calculated using the MSBase registry. Patients with incomplete data or <1 year of follow-up were excluded. Patients with primary progressive multiple sclerosis were only included in the sex ratio analysis. Relapse incidences over 40 years of multiple sclerosis or 70 years of age were compared between females and males with Andersen-Gill and Tweedie models. Female-to-male ratios stratified by annual relapse count were evaluated across disease duration and patient age and compared between relapse-onset and primary progressive multiple sclerosis. The study cohort consisted of 11 570 eligible patients with relapse-onset and 881 patients with primary progressive multiple sclerosis. Among the relapse-onset patients (82 552 patient-years), 48 362 relapses were recorded. Relapse frequency was 17.7% higher in females compared with males. Within the initial 5 years, the female-to-male ratio increased from 2.3:1 to 3.3:1 in patients with 0 versus ≥4 relapses per year, respectively. The magnitude of this sex effect increased at longer disease duration and older age (P < 10−12). However, the female-to-male ratio in patients with relapse-onset multiple sclerosis and zero relapses in any given year was double that of the patients with primary progressive multiple sclerosis. Patient age was a more important determinant of decline in relapse incidence than disease duration (P < 10−12). Females are predisposed to higher relapse activity than males. However, this difference does not explain the markedly lower female-to-male sex ratio in primary progressive multiple sclerosis. Decline in relapse activity over time is more closely related to patient age than disease duration.
