Immune Checkpoint Inhibitors and Pregnancy: Analysis of the VigiBase(®) Spontaneous Reporting System

SIMPLE SUMMARY: In preclinical studies, it has been shown that the blockade of immune checkpoint pathways increases the risk of fetal death. Therefore, the use of immune checkpoint inhibitors (ICIs) in cancer patients who are either pregnant or of childbearing potential is not recommended. Nevertheless, some clinical cases have been published showing positive pregnancy-related outcomes. To characterize the ICI safety profile in pregnancy, we used VigiBase(®), the World Health Organization’s spontaneous reporting system, and described 103 safety reports referring to ICI exposure during the peri-pregnancy period. Of these, 56 reported pregnancy-related outcomes, including spontaneous abortion, fetal growth restriction, and prematurity, for which we did not find signals of disproportionate reporting. Considering the expanding indications of ICIs, continuous surveillance by clinicians and pharmacovigilance experts is warranted. ABSTRACT: In pregnancy, immune checkpoint pathways are involved in the maintenance of fetomaternal immune tolerance. Preclinical studies have shown that immune checkpoint inhibitors (ICIs) increase the risk of fetal death. Despite the fact that using ICIs in pregnant women and women of childbearing potential is not recommended, some case reports of ICI exposure in pregnancy have been published showing favorable fetal outcomes. This study aimed to gain further insight into ICI safety in pregnancy by querying VigiBase(®), the World Health Organization’s spontaneous reporting system. We performed raw and subgroup disproportionality analyses using the reporting odds ratio and comparing ICIs with the entire database, other antineoplastic agents, and other antineoplastic agents gathered in VigiBase(®) since 2011. Across 103 safety reports referring to ICI exposure during the peri-pregnancy period, 56 reported pregnancy-related outcomes, of which 46 were without concomitant drugs as potential confounding factors. No signals of disproportionate reporting were found for spontaneous abortion, fetal growth restriction, and prematurity. In light of the expanding indications of ICIs, continuous surveillance by clinicians and pharmacovigilance experts is warranted, along with pharmacoepidemiological studies on other sources of real-world evidence, such as birth records, to precisely assess ICI exposure during the peri-pregnancy period and further characterize relevant outcomes.