Sex differences in multiple sclerosis treatment with disease modifying drugs: a step towards gender neurology

Introduction: Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of the central nervous system. Relevant differences between men and women are known in MS epidemiology, disease course, clinical manifestations and instrumental findings. However, differences in response to disease-modifying treatments (DMTs) have been rarely assessed. Methods: We performed a registry-based study on patients of our reference center in Palermo, Italy. Only patients with relapsing-remitting course or clinically isolated syndrome were included. Efficacy endpoints we considered were confirmed disease progression risk, first relapse risk and magnetic resonance imaging active lesion risk during treatment with each DMT. An exploratory analysis on annualized relapse risk was also performed. For safety analysis, withdrawal due to adverse events was considered. Cox multivariable survival analysis was performed to assess the impact of sex on each endpoint. Results: one thousand eight hundred five records were retrieved. However, due to low sample size, only data regarding some drugs (dimethylfumarate, glatiramer acetate, beta interferon and partially natalizumab and S1PR modulators) were analyzed. No significant differences between the two sexes were found for efficacy endpoints. Men showed a significantly lower risk of withdrawal from glatiramer acetate due to adverse events than women (p = 0.002, hazard ratio 0.32, 95 %confidence interval 0.16–0.65); dyspnea was the most frequent cause of interruption in both sexes. Discussion and conclusion: Our results show limited differences in response to DMTs between men and women for the drugs we took into account. Interpretation of these findings is challenging due to limited evidence available about this topic and to sexual dysmorphism involving many aspects of the disease. Small sample size, preventing the analysis of other DMTs (especially high-efficacy ones) and disease courses, is the main limit of this study. Further evidence will be needed in the future.