PT - JOURNAL ARTICLE AU - Stahl, Mirjam AU - Dohna, Martha AU - Graeber, Simon Y. AU - Sommerburg, Olaf AU - Renz, Diane M. AU - Pallenberg, Sophia T. AU - Voskrebenzev, Andreas AU - Schütz, Katharina AU - Hansen, Gesine AU - Doellinger, Felix AU - Steinke, Eva AU - Thee, Stephanie AU - Röhmel, Jobst AU - Barth, Sandra AU - Rückes-Nilges, Claudia AU - Berges, Julian AU - Hämmerling, Susanne AU - Wielpütz, Mark O. AU - Naehrlich, Lutz AU - Vogel-Claussen, Jens AU - Tümmler, Burkhard AU - Mall, Marcus A. AU - Dittrich, Anna-Maria TI - Impact of Elexacaftor/Tezacaftor/Ivacaftor Therapy on Lung Clearance Index and Magnetic Resonance Imaging in Children with Cystic Fibrosis and One or Two <strong><em>F508del</em></strong> Alleles AID - 10.1183/13993003.00004-2024 DP - 2024 Jan 01 TA - European Respiratory Journal PG - 2400004 4099 - https://publications.ersnet.org//content/early/2024/05/29/13993003.00004-2024.short 4100 - https://publications.ersnet.org//content/early/2024/05/29/13993003.00004-2024.full AB - Background We recently demonstrated that elexacaftor/tezacaftor/ivacaftor (ETI) improves the lung clearance index (LCI) and abnormalities in lung morphology detected by magnetic resonance imaging (MRI) in adolescent and adult patients with cystic fibrosis (CF). However, real-world data on the effect of ETI on these sensitive outcomes of lung structure and function in school-age children with CF have not been reported. The aim of this study was therefore to examine the effect of ETI on the LCI and the lung MRI score in children with CF and one or two F508del alleles aged 6 to 11 years.Methods This prospective, observational, multicenter, post-approval study assessed the longitudinal LCI up to 12 months and the lung MRI score before and three months after initiation of ETI.Results A total of 107 children with CF including 40 heterozygous for F508del and a minimal function mutation (F/MF) and 67 homozygous for F508del (F/F) were enrolled in this study. Treatment with ETI improved the LCI in F/MF children (−1.0; IQR, −2.0 to −0.1; p&lt;0.01) and F/F children (−0.8; IQR, −1.9 to −0.2; p&lt;0.001) from 3 months onwards. Further, ETI improved the MRI global score in F/MF (−4.0; IQR, −9.0 to 0.0; p&lt;0.01) and F/F children (−3.5; IQR, −7.3 to −0.8; p&lt;0.001).Conclusions ETI improves early abnormalities in lung ventilation and morphology in school-age children with CF and at least one F508del alleles in a real-world setting. Our results support early initiation of ETI to reduce or even prevent lung disease progression in school-age children with CF.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflicts of interest: M.S., S.Y.G. and S.T. are participants of the BIH-Charité Clinician Scientist Program and J.R. is participant of the Case Analysis and Decision Support (CADS) program funded by the Charité – Universitätsmedizin Berlin and the BIH.Conflicts of interest: M.S. reports an Independent Research Innovation Award and honoraria for lectures and participation in advisory boards, all by Vertex Pharmaceuticals Incorporated, outside of the submitted work. She is Chairman of the German CF Research Council (FGM), Treasurer of the German Society of Paediatric Pulmonology (GPP), and was Secretary of the Group CF of the Paediatric Assembly of the ERS.Conflicts of interest: M.D. is participant of the Ellen-Schmidt Habilitationsförderung funded by the Hannover Medical School.Conflicts of interest: S.Y.G. reports grants from the German CF Foundation and Vertex Pharmaceuticals Incorporated, outside of the submitted work. Additionally, he reports honoraria from Chiesi GmbH and Vertex Pharmaceuticals Incorporated for lectures and participation in advisory boards, outside of the submitted work.Conflicts of interest: O.S. reports grants and honoraria from Vertex Pharmaceuticals Incorporated for lectures, outside of the submitted work.Conflicts of interest: S.T.P. is a member of the Else-Kröner Forschungskolleg TITUS.Conflicts of interest: A.V. reports a grant and honoraria for lectures from Siemens Healthineers, outside of the submitted work. He holds a patent for a method of quantitative magnetic resonance lung imaging (Voskrebenzev, Gutberlet, VogelClaussen; Nr. EP3107066, US-2016-0367200-Al 22.12.2016). He is a stockholder and CEO of BioVisioneers GmbH.Conflicts of interest: K.S. reports payments for attending meetings and/or travel from Vertex Pharmaceuticals Incorporated, outside of the submitted work.Conflicts of interest: G.H. reports receipt of consultation fees from Sanofi GmbH, outside of the submitted work.Conflicts of interest: F.D. reports payment or honoraria for lectures, presentations, manuscript writing or educational events from Bayer, Bayer Vital, Berlin-Chemie Menarini, Boehringer Ingelheim, and Chiesi GmbH, payment for expert testimony from Calyx, support for attending meetings from Bayer.Conflicts of interest: E.S. reports grants from Berlin Institute of Health at Charité Berlin, payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceuticals Inc.Conflicts of interest: S.T. reports honoraria for lectures and payment for attending meetings and/or travel from Vertex Pharmaceuticals Incorporated and Viatris, outside of the submitted work.Conflicts of interest: J.R. reports honoraria for lectures from Vertex Pharmaceuticals Incorporated, outside the submitted work. Additionally, he is work package leader in BEAT-PCD (ERS-CRC).Conflicts of interest: M.O.W. reports a grant from Vertex Pharmaceuticals Incorporated, outside of the submitted work. Additionally, he reports receipt of consulting fees and honoraria for lectures from Vertex Pharmaceuticals Incorporated and Boehringer Ingelheim, outside of the submitted work.Conflicts of interest: L.N. reports receipt of fees for a data quality project of the German CF Registry. He is the medical lead of the German CF Registry, the pharmacovigilance study manager of the European Cystic Fibrosis Society Patient Registry, and part of the Trial Steering Committee for CF STORM. He also reports grants from German Center for Lung Research, Vertex Pharmaceuticals and Mukoviszidose Institute, and receipt of medical writing services from Articulate Science.Conflicts of interest: J.V.-C. reports grants from BMBF, Siemens Healthineers, AstraZeneca, Boehringer Ingelheim, and GSK, outside of the submitted work. He reports royalties or licenses from Siemens Healthineers, outside of the submitted work. Additionally, he reports receipt of consulting fees from AstraZeneca and honoraria for lectures from Siemens Healthineers, AstraZeneca, Boehringer Ingelheim, GSK, Roche, Coreline Soft, and Bayer, outside of the submitted work. Furthermore, he reports payments for attending meetings and/or travel from Vertex Pharmaceuticals Incorporated, Bayer, GSK, and AstraZeneca, outside of the submitted work. He holds a patent for a method of quantitative magnetic resonance lung imaging (Voskrebenzev, Gutberlet, Vogel-Claussen; Nr. EP3107066, US-2016-0367200-Al 22.12.2016).Conflicts of interest: B.T. reports support for the present study from Bundesministerium für Forschung und Technologie, grants from German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; CRC 900; Excellence cluster “RESIST”), consultancy fees from Helmholtz Institut für Infektionsforschung, payment or honoraria for lectures, presentations, manuscript writing or educational events from Vertex Pharmaceutical (Germany) Inc, participation on a data safety monitoring board or advisory board with Vertex Pharmaceuticals Inc, and leadership roles with Christiane Herzog Stiftung and Microbiome/Metagenome Group of the DZL.Conflicts of interest: M.A.M. reports grants from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG; SFB-TR 84, and project #450557679) and the German Innovation Fund (01NVF19008) outside of the submitted work. Additionally, he reports receipt of consulting fees from Abbvie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Prieris, Recode, Santhera, Splisense, and Vertex Pharmaceuticals Incorporated, of honoraria for lectures from Vertex Pharmaceuticals Incorporated and participation in advisory boards from Abbvie, Antabio, Arrowhead, Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotec, Pari, Vertex Pharmaceuticals Incorporated, and of payment for travel from Vertex Pharmaceuticals Incorporated and Boehringer Ingelheim, all outside of the submitted work. He is a Fellow of ERS (FERS).Conflicts of interest: A.-M.D. reports support for the present study from German Center for Lung Research (DZL), Vertex Pharm. Inc. and European Cystic Fibrosis Society – Clinical Trial Network, grants from Vertex Pharm. Inc., European Cystic Fibrosis Society – Clinical Trial Network, Forschungsgemeinschaft (DFG) and Christiane-Herzog-Stiftung, consultancy fees from c4c consortium, GSK and European Cystic Fibrosis Society.Conflicts of interest: All other authors have nothing to disclose.