CFTR during pregnancy and adverse drug reactions: A pharmacovigilance disproportionality analysis in VigiBase

Abstract

Background: Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have transformed the management of cystic fibrosis (CF), but evidence on their safety during pregnancy remains limited and pregnancy-related adverse drug reactions (ADRs) are not well characterized.

Methods: We analyzed VigiBase, the World Health Organization global pharmacovigilance database of individual case safety reports (ICSRs), to identify signals of disproportionate reporting (SDRs) for pregnancy-related ADRs associated with elexacaftor, ivacaftor, tezacaftor and lumacaftor, reported until 15 December 2024.

Results: Of 1035 pregnancy-related ICSRs with CFTR modulators, 280 met inclusion criteria. Two SDRs were identified: spontaneous abortion (n = 96 events, reporting odds ratio [ROR] 2.43; 95% confidence interval [CI] 1.99-2.97) and pre-eclampsia (n = 17 events, ROR 4.29; 95% CI 2.66-6.92). Reported birth defects were heterogeneous, with no recurring patterns. There was no SDR for prematurity. These findings align with recent observational studies and preclinical data indicating no teratogenic effects of CFTR modulators.

Conclusion: CFTR modulators were not associated with the reporting of consistent patterns of congenital anomalies or prematurity in this large pharmacovigilance analysis. SDRs for spontaneous abortion and pre-eclampsia should be interpreted cautiously given the limitations inherent to the used study design and require confirmation in prospective pregnancy registries and controlled studies.

Keywords: CFTR modulators; Disproportionality; Pharmacovigilance; Pregnancy; VigiBase.