| アブストラクト | BACKGROUND: Pulmonary arterial hypertension (PAH) has been described in patients treated with proteasome inhibitors (PIs). Our objective was to evaluate the association between PIs and PAH. METHODS: Characteristics of incident PAH cases previously treated with carfilzomib or bortezomib were analysed from the French pulmonary hypertension registry and the VIGIAPATH programme from 2004 to 2023, concurrently with a pharmacovigilance disproportionality analysis using the World Health Organization (WHO) global database (VigiBase) and a meta-analysis of randomised controlled trials. RESULTS: 11 incident cases of PI-associated PAH were identified (six with carfilzomib and five with bortezomib) with a female:male ratio of 2.7:1, a median age of 61 years, and a median delay between PI first exposure and PAH of 6 months. Four patients died (two from right heart failure, one from respiratory distress and one from an unknown cause). At diagnosis, six were in New York Heart Association Functional Class III/IV with severe haemodynamic impairment (median mean pulmonary arterial pressure 39 mmHg, cardiac index 2.45 L.min(-1).m(-2) and pulmonary vascular resistance 7.2 WU). In the WHO pharmacovigilance database, 169 cases of PH associated with PI were reported since 2013 with significant signals of disproportionate reporting (SDR) for carfilzomib, regardless of the definition of cases or control group. However, SDR for bortezomib were inconsistent. The systematic review identified 17 clinical trials, and carfilzomib was associated with a significantly higher risk of dyspnoea, severe dyspnoea and PH compared with bortezomib. CONCLUSION: PIs may induce PAH in patients undergoing treatment, with carfilzomib emitting a stronger signal than bortezomib, and these patients should be monitored closely. |
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| 投稿者 | Grynblat, Julien; Khouri, Charles; Hlavaty, Alex; Jais, Xavier; Savale, Laurent; Chaumais, Marie Camille; Kularatne, Mithum; Jevnikar, Mitja; Boucly, Athenais; Antigny, Fabrice; Perros, Frederic; Simonneau, Gerald; Sitbon, Olivier; Humbert, Marc; Montani, David |
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| 組織名 | INSERM UMR_S 999 "Pulmonary Hypertension: Pathophysiology and Novel Therapies",;Hopital Marie Lannelongue, Le Plessis-Robinson, France.;AP-HP, Department of Respiratory and Intensive Care Medicine, Pulmonary;Hypertension National Referral Centre, Bicetre Hospital, Le Kremlin-Bicetre,;France.;School of Medicine, University of Paris-Saclay, Le Kremlin-Bicetre, France.;These authors contributed equally to this work.;Univ. Grenoble Alpes, HP2 Laboratory, INSERM U 1300, Grenoble, France.;Pharmacovigilance Unit and Clinical Pharmacology Department, Grenoble Alpes;University Hospital, Grenoble, France.;School of Pharmacy, University of Paris-Saclay, Saclay, France.;AP-HP, Department of Pharmacy, Bicetre Hospital, Le Kremlin-Bicetre, France.;Division of Respiratory Medicine, Department of Medicine, University of Calgary,;Calgary, AB, Canada.;CarMeN Laboratory, INSERM U1060, INRAE U1397, Universite Claude Bernard Lyon 1,;Pierre-Benite, France.;Hopital Marie Lannelongue, Le Plessis-Robinson, France david.montani@aphp.fr. |
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