Safety of belimumab during pregnancy: associations with maternal and fetal or newborn adverse outcomes based on FAERS data

Background: Belimumab is a biologic agent used in the treatment of systemic lupus erythematosus (SLE). However, its safety profile during pregnancy has not been fully established, and real-world evidence regarding its association with adverse pregnancy outcomes remains limited. Objectives: To evaluate the safety of belimumab during pregnancy and explore its potential associations with maternal and fetal/neonatal adverse events. Design: Retrospective pharmacovigilance study. Methods: Disproportionality analysis of pregnancy-related individual case safety reports (ICSRs) from the FDA Adverse Event Reporting System (FAERS), Q2 2011-Q4 2024. Pregnancy-related cases were identified using Standardized MedDRA Queries. Belimumab was the primary suspected drug, with hydroxychloroquine and mycophenolate mofetil as negative and positive controls, respectively. Signal detection employed the reporting odds ratio (ROR); stratified analyses assessed potential confounding factors. Results: A total of 263,400 ICSRs was identified, including 537 belimumab, 1033 hydroxychloroquine, and 1039 mycophenolate mofetil. Most belimumab-related cases were reported from North America (78.40%), with SLE as the primary indication (71.88%). Disproportionality analysis revealed significant reporting of abortion (ROR 2.15, 95% confidence interval (CI) 1.76-2.63), hypertensive disorders of pregnancy (ROR 2.20, 95% CI 1.32-3.66), and pregnancy-related hemorrhagic complications (ROR 2.19, 95% CI 1.09-4.40), but not for stillbirth, preterm birth, or congenital malformations. A neonatal respiratory disorder signal was also observed (ROR 6.50, 95% CI 2.90-14.53). The hypertensive disorder signal was amplified with concomitant glucocorticoid use, suggesting confounding by disease severity. Mycophenolate mofetil, as a positive control, generated expected signals for adverse pregnancy outcomes and congenital anomalies, validating method sensitivity. Conclusion: Belimumab exposure during pregnancy is not associated with a significantly elevated risk of stillbirth, preterm birth, or overall congenital malformations. Conversely, disproportionality signals were detected for abortion, hypertensive disorders of pregnancy, hemorrhagic complications, and neonatal respiratory disorders. These signals warrant cautious interpretation, as they may partially reflect the elevated baseline risk intrinsic to the high-risk SLE patient population.