title: Sex as a determinant of relapse incidence and progressive course of multiple sclerosis.
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.
authors.affiliation: 1 Department of Medicine, University of Melbourne, Melbourne, Australia.
authors.forename: Tomas
authors.initials: T
authors.lastname: Kalincik
authors.forename: Vino
authors.initials: V
authors.lastname: Vivek
authors.forename: Vilija
authors.initials: V
authors.lastname: Jokubaitis
authors.forename: Jeannette
authors.initials: J
authors.lastname: Lechner-Scott
authors.forename: Maria
authors.initials: M
authors.lastname: Trojano
authors.forename: Guillermo
authors.initials: G
authors.lastname: Izquierdo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Lugaresi
authors.forename: Francois
authors.initials: F
authors.lastname: Grand'maison
authors.forename: Raymond
authors.initials: R
authors.lastname: Hupperts
authors.forename: Celia
authors.initials: C
authors.lastname: Oreja-Guevara
authors.forename: Roberto
authors.initials: R
authors.lastname: Bergamaschi
authors.forename: Gerardo
authors.initials: G
authors.lastname: Iuliano
authors.forename: Raed
authors.initials: R
authors.lastname: Alroughani
authors.forename: Vincent
authors.initials: V
authors.lastname: Van Pesch
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Amato
authors.forename: Mark
authors.initials: M
authors.lastname: Slee
authors.forename: Freek
authors.initials: F
authors.lastname: Verheul
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fernandez-Bolanos
authors.forename: Marcela
authors.initials: M
authors.lastname: Fiol
authors.forename: Daniele La
authors.initials: DL
authors.lastname: Spitaleri
authors.forename: Edgardo
authors.initials: E
authors.lastname: Cristiano
authors.forename: Orla
authors.initials: O
authors.lastname: Gray
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Cabrera-Gomez
authors.forename: Vahid
authors.initials: V
authors.lastname: Shaygannejad
authors.forename: Joseph
authors.initials: J
authors.lastname: Herbert
authors.forename: Steve
authors.initials: S
authors.lastname: Vucic
authors.forename: Merilee
authors.initials: M
authors.lastname: Needham
authors.forename: Tatjana
authors.initials: T
authors.lastname: Petkovska-Boskova
authors.forename: Carmen-Adella
authors.initials: CA
authors.lastname: Sirbu
authors.forename: Pierre
authors.initials: P
authors.lastname: Duquette
authors.forename: Marc
authors.initials: M
authors.lastname: Girard
authors.forename: Pierre
authors.initials: P
authors.lastname: Grammond
authors.forename: Cavit
authors.initials: C
authors.lastname: Boz
authors.forename: Giorgio
authors.initials: G
authors.lastname: Giuliani
authors.forename: Maria Edite
authors.initials: ME
authors.lastname: Rio
authors.forename: Michael
authors.initials: M
authors.lastname: Barnett
authors.forename: Shlomo
authors.initials: S
authors.lastname: Flechter
authors.forename: Fraser
authors.initials: F
authors.lastname: Moore
authors.forename: Bhim
authors.initials: B
authors.lastname: Singhal
authors.forename: Elizabeth Alejandra
authors.initials: EA
authors.lastname: Bacile
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Saladino
authors.forename: Cameron
authors.initials: C
authors.lastname: Shaw
authors.forename: Eli
authors.initials: E
authors.lastname: Skromne
authors.forename: Dieter
authors.initials: D
authors.lastname: Poehlau
authors.forename: Norbert
authors.initials: N
authors.lastname: Vella
authors.forename: Timothy
authors.initials: T
authors.lastname: Spelman
authors.forename: Danny
authors.initials: D
authors.lastname: Liew
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Kilpatrick
authors.forename: Helmut
authors.initials: H
authors.lastname: Butzkueven
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D006801:Humans; D015994:Incidence; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000453:epidemiology*; D012008:Recurrence; D012189:Retrospective Studies; D012727:Sex Characteristics
keywords: MSBase; multiple sclerosis; prediction; risk factors; sex