Safety of Multiple Sclerosis Treatments During Pregnancy: An Overview of the EU Regulatory Approach to Risk Management Planning

PURPOSE: Multiple Sclerosis (MS) may affect women of childbearing age. Information on safety of disease modifying treatment (DMT) in pregnancy is often limited at time of marketing authorisation. We summarised the EU regulatory experience with the implementation and performance of additional pharmacovigilance activities concerning safety in pregnancy and breastfeeding for medicines to treat MS. METHODS: We reviewed EU risk management plans (RMPs) for centrally authorised MS DMTs to identify additional pharmacovigilance activities related to pregnancy and breastfeeding. Information was analysed descriptively for type of measure, data collection method and data source. For non-interventional cohort studies and follow-up of reported pregnancy cases, information on current status, planned and actual size and duration was retrieved. RESULTS: We identified 17 DMTs that included 21 additional pharmacovigilance activities related to pregnancy and breastfeeding across 15 RMPs. These comprised nine non-interventional cohort studies and four structured follow-up activities of pregnancy cases that had been started. Of those, three were terminated due to low recruitment with an inclusion rate slower than planned, while inclusion was faster than planned in three finalised activities. Inclusion rate was slowest in primary data collection and faster in secondary analyses and follow-up of reported pregnancy cases. CONCLUSION: Despite efforts to evaluate safety of MS medicines during pregnancy, recruitment and data collection remain challenging. Planning for use of multiple real-world data sources-including primary data collection, secondary use of electronic health records, and analyses of case reports-may help overcome these challenges and strengthen MS drug safety evaluations in pregnancy.