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.

Increasing Incidence in Relapsing-Remitting MS and High Rates among Young Women in Finland: A Thirty-Year Follow-Up

“…These effects causing increased disease risk may be present already during the fetal period and in the childhood, supported by the fivefold F/M ratio among RRMS cases younger than 20 years as was seen in this study. This result corroborates observations of a higher relapse rate among females and the effect of age and disease duration on disease activity [33]. …”

Multiple Sclerosis Relapses: Epidemiology, Outcomes and Management. A Systematic Review

“…A number of previous studies, including large cohort studies and a meta-analysis of 33 observational studies of patients with CIS consistently showed that females are more likely to experience relapses throughout the course of the disease [42][43][44] ( table 1 ). Relapse incidence is known to decrease with time, represented either by patient age or by MS duration [20,42,[44][45][46][47][48] .…”

“…Relapse incidence is known to decrease with time, represented either by patient age or by MS duration [20,42,[44][45][46][47][48] . In a direct comparison of the effects of these largely collinear determinants of relapse frequency, we showed that older age is relatively more closely associated with decline in relapse activity than MS duration [42] . Interestingly, our study suggested that an interaction between sex-and time-dependent changes in relapse frequency may exist, with the attenuation of relapse activity delayed in females com- pared to males.…”

Comparative effectiveness of glatiramer acetate and interferon beta formulations in relapsing–remitting multiple sclerosis

“…[9][10][11] We have recently demonstrated feasibility of propensitybased matching for evaluation of treatment effectiveness in the MSBase dataset, showing that two dosages of IFNβ-1a SC were equivalent in relapse rate and disability outcomes, thus mirroring the outcomes of the pivotal registration study. 12,13 Here we present a propensity score-matched analysis comparing the effectiveness of IFNβ and GA preparations in a series of pairwise head-to-head cohort studies conducted in MSBase.…”