Published: 10 May 2022

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-Nilges, Mark O. Wielpütz, Gesine Hansen, Jens Vogel-Claussen, Burkhard Tümmler, Marcus A. Mall, and Anna-Maria Dittrich

Source: This abstract has been sourced from NZ Respiratory Research Review Issue 203


    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 (−2.4; interquartile range [IQR], −3.7 to −1.1; P < 0.001) and F508del homozygous (−1.4; IQR, −2.4 to −0.4; P < 0.001) patients. Furthermore, ELX/TEZ/IVA improved the MRI global score in F508del/MF (−6.0; IQR, −11.0 to −1.3; P < 0.001) and F508del homozygous (−6.5; IQR, −11.0 to −1.3; 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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