Effects of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Patients with Cystic Fibrosis and One or Two F508del Alleles

• DOI: 10.1164/rccm.202201-0219oc
• Publication Date: 2022-05-10T15:04:25Z
• Authors: Simon Y. Graeber; Diane M. Renz; Mirjam Stahl; Sophia T. Pallenberg; Olaf Sommerburg; Lutz Naehrlich; Julian Berges; Martha Dohna; Felix C. Ringshausen; Felix Doellinger; Constanze Vitzthum; Jobst Röhmel; Christine Allomba; Susanne Hämmerling; Sandra Barth; Claudia Rückes-Ni...; Mark O. Wielpütz; Gesine Hansen; Jens Vogel-Claussen; Burkhard Tümmler; Marcus A. Mall; Anna-Maria Dittrich
• Keywords: Ivacaftor; Interquartile range; Compound heterozygosity

Rationale: We recently demonstrated that triple-combination CFTR (cystic fibrosis transmembrane conductance regulator) modulator therapy with elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves function in airway and intestinal epithelia to 40–50% of normal patients cystic (CF) one or two F508del alleles. In previous studies, this improvement was shown improve clinical outcomes; however, effects on the lung clearance index (LCI) determined by multiple-breath washout abnormalities morphology perfusion detected magnetic resonance imaging (MRI) have not been studied. Objectives: To examine effect ELX/TEZ/IVA LCI MRI scores CF alleles aged ⩾12 years. Methods: This prospective, observational, multicenter, postapproval study assessed before 8–16 weeks after initiation ELX/TEZ/IVA. Measurements Main Results: A total 91 CF, including 45 heterozygous for a minimal mutation (MF) 46 homozygous F508del, were enrolled study. Treatment improved F508del/MF (−2.4; interquartile range [IQR], −3.7 −1.1; P < 0.001) (−1.4; IQR, −2.4 −0.4; patients. Furthermore, global score (−6.0; −11.0 −1.3; (−6.5; Conclusions: Our data demonstrate ventilation morphology, mucus plugging wall thickening, adolescent adult real-world, setting. Clinical trial registered www.clinicaltrials.gov (NCT04732910).