Gender trends in Multiple Sclerosis over the last 25 years: Real-World Evidence from the Italian Multiple Sclerosis and Related Disorders Register

Introduction Sex and gender play a relevant role in several diseases at many levels. Greater attention to the actual differences in men’s and women’s health risks, health status, and access to services is critically important for improving the performance of health systems. Without explicit attention to the different health needs of men and women, equitable goals in terms of access to care and treatment will be difficult to achieve. Objectives To analyze differences between males and females in treatment and clinical outcomes of people with MS (pwMS) registered in the Italian Multiple Sclerosis and Related Disorders Register (RISM). Methods Data from 11,208 male and 22,414 female pwMS with onset after 2000 and complete sociodemographic and clinical information were extracted from the RISM. A 1:1 propensity score matching analysis was conducted using logistic regression, with first EDSS assessment, age at onset, first disease course, year of first DMT prescription, and follow-up as covariates. Results The matching led to 11,208 pairs. The median time from onset to diagnosis was approximately 9 months for both sexes. The median time from diagnosis to the first DMT prescription was 2.6 months for males and 2.8 months for females (p-value <0.0001). Significant differences were found in the DMT administration modalities (injection: 64.9% males vs 67.4% females; oral: and 23.6% males vs 21.4% females), last disease course (relapsing remitting: 84.8% males vs 87.0% females secondary progressive: 7.8% males vs 5.7% females), last EDSS (low: 69.0% males vs 71.0% females; high 7.2% males vs 5.8% females) and annualized relapse rate (median AAR: 0.24 in males and 0.27 in females). Conclusions After propensity score matching, significant differences between males and females emerged, consistent with patterns well-documented in the existing literature. Females were more likely to develop a relapsing remitting MS course, whereas males were more prone to develop a secondary progressive MS. This is critically linked to a higher AAR in women and a higher last EDSS score in men. Despite a significant difference between times from diagnosis to first DMT (±0.33 months), this data lacks of clinical relevance. Notably, differences in DMT administration were observed, with males receiving more oral and fewer injection drugs than females. These findings suggest that, within this cohort, gender disparities do not appear to influence the access to or quality of MS care.