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

Abstract

Introduction: 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.

Methods: 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.

Results: 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).

Conclusions: 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.