Journal
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
Volume 206, Issue 3, Pages 311-320Publisher
AMER THORACIC SOC
DOI: 10.1164/rccm.202201-0219OC
Keywords
CFTR modulator therapy; cystic fibrosis; magnetic resonance imaging; multiple-breath washout; elexacaftor/tezacaftor/ivacaftor
Categories
Funding
- Vertex Pharmaceuticals Inc. [IIS-2018-107555]
- German Center for Lung Research - Bundesministerium fur Bildung und Forschung [82DZL009B1, 82DZL002A1, 82DZL005B1, 82DZL004B1]
- Deutsche Forschungsgemeinschaft [CRC 1449 - 431232613 Z02]
- Charite - Universitatsmedizin Berlin
- BIH
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ELX/TEZ/IVA improves CFTR function in patients with cystic fibrosis, leading to improved lung ventilation and morphology.
Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves CFTR function in airway and intestinal epithelia to 40-50% of normal in patients with cystic fibrosis (CF) with one or two F508del alleles. In previous studies, this improvement of CFTR function was shown to improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout and abnormalities in lung morphology and perfusion detected by magnetic resonance imaging (MRI) have not been studied. Objectives: To examine the effect of ELX/TEZ/IVA on LCI and lung MRI scores in patients with CF and one or two F508del alleles aged >= 12 years. Methods: This prospective, observational, multicenter, postapproval study assessed LCI and lung MRI scores before and 8-16 weeks after initiation of ELX/TEZ/IVA. Measurements and Main Results: A total of 91 patients with CF, including 45 heterozygous for F508del and a minimal function mutation (MF) and 46 homozygous for F508del, were enrolled in this study. Treatment with ELX/TEZ/IVA improved LCI in F508del/MF (22.4; interquartile range [IQR], 23.7 to 21.1; P < 0.001) and F508del homozygous (21.4; IQR, 22.4 to 20.4; P < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in F508del/MF (26.0; IQR, 211.0 to 21.3; P < 0.001) and F508del homozygous (26.5; IQR, 211.0 to 21.3; P < 0.001) patients. Conclusions: Our data demonstrate that improvement of CFTR function by ELX/TEZ/IVA improves lung ventilation and abnormalities in lung morphology, including airway mucus plugging and wall thickening, in adolescent and adult patients with CF and one or two F508del alleles in a real-world, postapproval setting.
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