(259) A Multi-Source Approach to Pregnancy and Lactation Evidence Generation in Multiple Sclerosis: The Ocrelizumab Example

Background: Pregnant and breastfeeding women are often excluded from pivotal clinical trials, leaving clinical decisions regarding new medications based on assumed pharmacological mechanisms. Post-marketing safety data can provide critical information to assess the benefit-risk profile of treatments during pregnancy and breastfeeding and improve patient care

Objectives: This review will use the example of ocrelizumab, an anti-CD20 monoclonal antibody targeting CD20-positive B cells for the treatment of multiple sclerosis (MS), to highlight the advantages and challenges of multi-source data (post-marketing studies and pharmacovigilance activities) to investigate the benefit-risk profile of medications in pregnant and lactating women.

Methods: Roche, the market authorization holder, performed enhanced post-marketing surveillance of pregnancy and lactation data, thereby involving medical field and safety personnel. This data was obtained through various channels, including interventional and non-interventional studies/programs, spontaneous reports, and published literature and involved follow-up using specifically designed pregnancy and infant health care questionnaires. In addition, a series of post-marketing studies were implemented; a prospective pregnancy registry (NCT01194570), MELODIC (BA39732), a multi-database secondary data use study evaluating pregnancy and infant outcomes, and two prospective phase IV studies. The phase IV studies, known as MINORE (MN42988, placental transfer) and SOPRANINO (MN42989, breast milk transfer) focus on infant B-cell levels and pharmacokinetics.

Results: As of July 2023, 3,244 maternal-exposure pregnancies were reported. Since the first report in 2017, the number of reported pregnancies has continued to rise. There was a 62.0% increase in the number of cases reported from 2022 to 2023. Most cases (75.3%) were reported prospectively, and outcomes were known for 58.0% of pregnancies. Of the 1,481 live births, 1-year follow-up data was received for 400 infants.

Conclusions: Roche has established a robust PV process which has contributed to the largest dataset of pregnancy outcomes for an anti-CD20 therapy in MS. Although a substantial number of cases have been reported, many outcomes remain unknown, and often infant outcome reports are incomplete. Thus, active reporting by healthcare professionals and patients is imperative. High-quality data from interventional and non-interventional studies combined with PV data can complement the understanding of a drug's safety profile in pregnant or breastfeeding women and their infants. The collection and continuous reporting of this data empower patients and clinicians to make evidence-based decisions that optimize care for women and infants.