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

Abstract

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 (BMPR2 mutation, portal hypertension or COPD). In the SNDS cohort of 9964 PAH patients, 30 had prior bevacizumab exposure, with no increased incidence compared to the general population. In VigiBase, 21 PAH cases were reported with bevacizumab, yielding a modest disproportionality signal only under broad definitions (IC 0.4 (95% credibility interval 0.1-0.6)).

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.