A case for gender-based approach to multiple sclerosis therapeutics

Despite established sex differences in multiple sclerosis (MS) risk and course, sex-specific efficacy and toxicity of existing MS therapies, and possible sex-specific therapeutic approaches, remain underexplored. We systematically reviewed published sex differences from Phase III pivotal trials for FDA or EMA-approved MS disease modifying therapies (DMTs), along with additional information from pharmaceutical companies, for pre-specified or post-hoc baseline characteristics, efficacy and safety outcomes by sex, and sex-specific concerns. Then, we reviewed trials testing hormonal therapies in MS. None of the Phase III clinical trials performed baseline sex specific analyses or were powered to evaluated DMTs in menopausal/older populations. Some recent trials performed pre-specified or post-hoc stratification of outcomes by sex. Sex-specific hormonal intervention trials were limited. Adequately powered, pre-specified analyses accounting for baseline sex and age are required to maximize safety and efficacy in specific patient populations.