期刊
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
卷 205, 期 5, 页码 540-549出版社
AMER THORACIC SOC
DOI: 10.1164/rccm.202110-2249OC
关键词
CFTR biomarker; cystic fibrosis; nasal potential difference; intestinal current measurement; elexacaftor/tezacaftor/ivacaftor
资金
- Vertex Pharmaceuticals Incorporated [IIS-2018-107555]
- German Center for Lung Research - German Federal Ministry of Education and Research [82DZL009B1, 82DZL002A1, 82DZL005B1, 82DZL004B1]
- Deutsche Forschungsgemeinschaft [SFB 1449-Z02 (431232613)]
- Charite-Universitatsmedizin Berlin
- BIH
Treatment with ELX/TEZ/IVA leads to effective improvement of CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles.
Rationale: The CFTR (cystic fibrosis transmembrane conductance regulator) modulator combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to improve clinical outcomes and sweat chloride concentration in patients with cystic fibrosis (CF) and one or two F508del alleles. However, the effect of ELX/TEZ/IVA on CFTR function in the airways and intestine has not been studied. Objectives: To assess the effect of ELX/TEZ/IVA on CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles aged 12 years and older. Methods: This prospective, observational, multicenter study assessed clinical outcomes including FEV1 % predicted and body mass index and the CFTR biomarkers sweat chloride concentration, nasal potential difference, and intestinal current measurement before and 8-16 weeks after initiation of ELX/TEZ/IVA. Measurements and Main Results: A total of 107 patients with CF including 55 patients with one F508del and a minimal function mutation and 52 F508del homozygous patients were enrolled in this study. In patients with one F508del allele, nasal potential difference and intestinal current measurement showed that ELX/TEZ/IVA improved CFTR function in nasal epithelia to a level of 46.5% (interquartile range [IQR], 27.5-72.4; P < 0.001) and in intestinal epithelia to 41.8% of normal (IQR, 25.1-57.6; P < 0.001). In F508del homozygous patients, ELX/TEZ/IVA exceeded improvement of CFTR function observed with TEZ/IVA and increased CFTR-mediated Cl secretion to a level of 47.4% of normal (IQR, 19.3-69.2; P < 0.001) in nasal and 45.9% (IQR, 19.7-66.6; P < 0.001) in intestinal epithelia. Conclusions: Treatment with ELX/TEZ/IVA results in effective improvement of CFTR function in airway and intestinal epithelia in patients with CF and one or two F508del alleles.
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