Use of biologics to treat asthma during pregnancy and adverse events in pregnant women and newborns: A global pharmacovigilance analysis

Despite the increasing evidence supporting the use of biologics for treating severe asthma, there is a lack of evidence regarding their use in pregnant women. This study aims to evaluate the safety of biologics for pregnant women, utilizing global pharmacovigilance database. Reports documented between 1980 and 2023 were extracted from the VigiBase that mentioned pregnancy- or fetus-related reactions with drugs indicated for asthma, including reslizumab, omalizumab, mepolizumab, dupilumab, benralizumab, and other non-biologics. A disproportionality analysis of case-non-case was conducted by calculating the reporting odds ratio (ROR) with 95% confidence interval (95% CI) of adverse maternal, fetal, and newborn outcomes associated with exposure to biologics compared with outcomes associated with other non-biologic asthma medications. A total of 15,715 pregnancy-related reports were analyzed. Reslizumab showed an overall lower reporting frequency of adverse events (ROR, 0.19; 95% CI, 0.05-0.67). Omalizumab (ROR, 3.88; 95% CI, 3.16-4.77), mepolizumab (ROR, 1.87; 95% CI, 1.05-3.36), and dupilumab (ROR, 5.34; 95% CI, 3.90-7.32) commonly showed higher frequencies of spontaneous fetal death. However, these three drugs also had lower frequencies of pregnancy and delivery complications, including preterm birth (omalizumab: ROR, 0.22; 95% CI, 0.16-0.31; mepolizumab: ROR, 0.10; 95% CI, 0.03-0.34; dupilumab: ROR, 0.07; 95% CI, 0.03-0.17), which are outcomes related to late pregnancy. In contrast, benralizumab (ROR, 0.69; 95% CI, 0.48-0.99) differed from the other biologics by showing lower frequencies of spontaneous fetal death (ROR, 0.69; 95% CI, 0.48-0.99) and spontaneous abortion (ROR, 0.47; 95% CI, 0.29-0.78) but higher frequencies of delivery complications (ROR, 1.32; 95% CI, 1.02-1.72), including preterm birth (ROR, 1.46; 95% CI, 1.14-1.86). This global case-non-case study underscores the critical need for further well-designed research to investigate these over-reported outcomes and emphasizes the importance of more rigorous monitoring efforts for these adverse events.