Abstract
OBJECTIVE: To describe the safety and efficacy of rituximab (RTX) in MS and pregnancy, we conducted a retrospective cohort study of 74 pregnancies among 55 women treated with RTX for MS and their offspring. METHODS: We used prospectively collected information from the electronic health record at Kaiser Permanente Southern California between 2012 and 2019 of mother and baby to identify treatment history, pregnancy outcomes, and relapses. RESULTS: Last RTX exposure before conception occurred between 1.8 and 5.2 months in 32 (49%) of 65 pregnancies and accidentally during the first trimester in 9 (12%). Among 38 live births, adverse pregnancy outcomes were as follows: 3 preterm deliveries (including 1 set of twins), 1 neonatal death (preterm twin), and 1 perinatal stroke (full-term). No stillbirths, chorioamnionitis, or major malformations were found. Fifteen (27%) women had at least one first-trimester miscarriage, of whom 8 (53%) had a history of infertility. Cumulative dose or timing of last RTX infusion was not associated with an increased risk of miscarriage. Only 2 (5.4%) women experienced relapses, one during pregnancy and the other postpartum. CONCLUSION: We observed no increase in adverse pregnancy outcomes compared with expected national incidence rates and remarkably little disease activity in RTX-treated women with MS, particularly when compared with periconceptional natalizumab-treated cohorts. However, larger studies are needed to fully assess the safety of RTX use before pregnancy, especially risks associated with prolonged B-cell depletion and hypogammaglobulinemia. Until these data are available, we recommend restricting RTX use before pregnancy to women who require highly effective MS treatments. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for pregnant women with MS, RTX controls disease activity and does not increase adverse pregnancy outcomes.