Characteristics and outcomes of patients developing pulmonary hypertension associated with proteasome inhibitors.
Eur Respir J
; 63(6)2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38697649
ABSTRACT
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 femalemale ratio of 2.71, a median age of 61â years, and a median delay between PI first exposure and PAH of 6â 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 39â mmHg, cardiac index 2.45 L·min-1·m-2 and pulmonary vascular resistance 7.2â 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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Inhibidores de Proteasoma
/
Bortezomib
/
Hipertensión Arterial Pulmonar
Límite:
Humans
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Eur Respir J
Año:
2024
Tipo del documento:
Article
País de afiliación:
Francia