| アブストラクト | 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 (Systeme National des Donnees de Sante (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. |
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| 投稿者 | Valentin, Simon; Hlavaty, Alex; Brossat, Coline; Chaumais, Marie-Camille; Artaud-Macari, Elise; Mauran, Pierre; Maurac, Arnaud; Savale, Laurent; Sitbon, Olivier; Humbert, Marc; Chaouat, Ari; Khouri, Charles; Montani, David |
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| 組織名 | Universite de Lorraine, CHRU de Nancy, Pole des Specialites Medicales/Departement;de Pneumologie, Nancy, France.;Universite de Lorraine, INSERM U1254 IADI, Nancy, France.;Univ. Grenoble Alpes, Inserm U1300, HP2, Grenoble, France.;Univ. Grenoble Alpes, Pharmacovigilance Unit and Clinical Pharmacology Department;(CIC-1406), Grenoble Alpes University Hospital, Grenoble, France.;Department of Pharmacy, Hopital Bicetre, AP-HP, Le Kremlin-Bicetre, France.;Faculty of Pharmacy, Universite Paris-Saclay, Orsay, France.;INSERM UMR_S1358, Pulmonary Hypertension: Pathophysiology and Novel Therapies,;Hopital Marie-Lannelongue and Hopital Bicetre, Le Kremlin-Bicetre, France.;Universite Rouen Normandie, GRHVN UR 3830, CHU Rouen, Department of Pulmonary,;Thoracic Oncology and Respiratory Intensive Care, Rouen, France.;CCMR PulmoTension, Hopital Robert Debre, CHU Reims, Reims, France.;Service des Maladies Respiratoires, Hopital Haut Leveque CHU de Bordeaux Pessac,;Pessac, France.;Faculty of Medicine, Universite Paris-Saclay, Le Kremlin-Bicetre, France.;Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension;National Referral Centre, FHU Andre Cournand, ERN-LUNG, Hopital Bicetre, AP-HP,;Le Kremlin-Bicetre, France.;Inserm-Universite de Lorraine, UMR 1116, Nancy, France.;C.Khouri and D. Montani contributed equally to this article as lead authors. |
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