OBJECTIVE: To assess the pregnancy and infant safety of ocrelizumab after maternal use in the 6 months before or during pregnancy in the setting of routine healthcare.
BACKGROUND: Ocrelizumab is a recombinant, humanized, monoclonal immunoglobulin G1 antibody that selectively targets CD20+ B cells. Immunoglobulins are known to cross the placental barrier, and women of childbearing age should use contraception while receiving ocrelizumab and for 6 months after the last infusion. Therefore, knowledge of how ocrelizumab exposure affects pregnancy and infant outcomes in humans is limited.
DESIGN/METHODS: This study will use multiple sources of data collected prospectively, including existing population-based healthcare registries from Denmark and three United States claims databases. Ocrelizumab-exposed pregnancies in women with multiple sclerosis (MS) will be compared with: (1) pregnancies in women with MS without ocrelizumab exposure; and (2) pregnancies in women without MS and no ocrelizumab exposure. The frequency of adverse pregnancy outcomes (including spontaneous abortions, stillbirths, elective abortions, preterm births, C-sections and urinary and other infections) and adverse infant outcomes (including major congenital malformations, small for gestational age, and adverse effects on immune system development) will be estimated and compared across matched cohorts (validation of selected outcomes may be conducted). Analyses will be conducted within each data source separately and subsequently pooled using meta-analytic techniques.
RESULTS: The observation period will start when ocrelizumab is first prescribed within one of the participating data sources (Q2 2017), and the study will be completed in Q1 2023.
CONCLUSIONS: This study will complement the planned Ocrelizumab Pregnancy Registry and address some known limitations of registries (e.g. slow enrollment, loss to follow-up), while generating important information on pregnancy and fetal outcomes following exposure to ocrelizumab. This information will be useful in guiding discussions between healthcare providers and women who may have been exposed to ocrelizumab before or during pregnancy.
