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.