Multimodal investigation of the association between bevacizumab and pulmonary arterial hypertension.

Background: Pulmonary arterial hypertension (PAH) is a rare and severe condition that may be associated with exposure to certain drugs. Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor, has been classified as having a possible association with PAH, but data remain scarce. This study aimed to assess the potential link between bevacizumab exposure and PAH through complementary clinical, medico-administrative and pharmacovigilance databases. Methods: We performed a multimodal investigation combining: 1) case identification from the French Pulmonary Hypertension (PH) Registry, 2) a population-based cohort analysis using the French National Health Data System (Système National des Données de Santé (SNDS)) and 3) a disproportionality analysis in the World Health Organization pharmacovigilance database (VigiBase). Clinical, haemodynamic and exposure data were reviewed in the French PH Registry; prevalence of PAH in patients exposed to bevacizumab was computed in the SNDS; and disproportionality analyses (information component (IC) values) were calculated in VigiBase. Results: Seven cases of PAH temporally associated with bevacizumab were identified in the French PH Registry, most displaying predisposing conditions ( Conclusions: Across complementary data sources, there was no evidence of a causal association between exposure to bevacizumab and the development of PAH in adults. However, the effect of bevacizumab as a secondary trigger in predisposed individuals cannot be definitely or completely excluded.