{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T09:12:19Z","timestamp":1782983539635,"version":"3.54.5"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T00:00:00Z","timestamp":1684886400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>A triple combination of CFTR modulators ELE\/TEZ\/IVA (elexacaftor\/tezacaftor\/ivacaftor, Trikafta\u2122) has been evaluated in clinical trials for people with cystic fibrosis (pwCF) and was approved to the European and US market. During registration and settling reimbursement in Europe, it could be requested on a compassionate use basis, for patients with advanced lung disease (ppFEV<jats:sub>1<\/jats:sub>\u2009&lt;\u200940).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aim<\/jats:title><jats:p>The aim of this study is to evaluate 2 years of experience with the clinical and radiological response of ELE\/TEZ\/IVA in pwCF in a compassionate use setting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>pwCF who started ELE\/TEZ\/IVA in a compassionate use setting were prospectively followed with assessment of spirometry, BMI, chest CT, CFQ\u2010R and sweat chloride concentration (SCC) before start and after 3 months. Furthermore, spirometry, sputum cultures, and BMI were repeated after 1, 6, 12, 18, and 24 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighteen patients were eligible for this evaluation, nine with F508del\/F508del genotype (eight of whom were using dual CFTR modulators) and nine with F508del\/minimal function mutation. After 3 months, mean change in SCC was \u221244.9 (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001), together with significant improvement in CT (change in Brody score: \u221228.27 <jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001) and CFQ\u2010R results (change in respiratory domain: +18.8, <jats:italic>p<\/jats:italic>\u2009=\u20090.002). After 24 months, ppFEV<jats:sub>1<\/jats:sub> change was +8.89 (<jats:italic>p<\/jats:italic>\u2009=\u20090.002), BMI had improved by +1.53\u2009kg\/m<jats:sup>2<\/jats:sup> (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001) and exacerbation rate declined from 5.94 in 24 months before start to 1.17 (<jats:italic>p<\/jats:italic>\u2009\u2264\u20090.001) in the 24 months after.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>pwCF with advanced lung disease experience relevant clinical benefit after 2 years of treatment with ELE\/TEZ\/IVA in a compassionate use setting. Structural lung damage, quality of life, exacerbation rate, and BMI improved significantly with treatment. Gain in ppFEV<jats:sub>1<\/jats:sub> is lower compared to the phase III trials that included younger patients with moderately affected lung function.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.26486","type":"journal-article","created":{"date-parts":[[2023,5,24]],"date-time":"2023-05-24T11:25:12Z","timestamp":1684927512000},"page":"2317-2322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Radiological and long\u2010term clinical response to elexacaftor\/tezacaftor\/ivacaftor in people with cystic fibrosis with advanced lung disease"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6125-0818","authenticated-orcid":false,"given":"Bente L.","family":"Aalbers","sequence":"first","affiliation":[{"name":"Department of Pulmonology, UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firdaus A. A.","family":"Mohamed Hoesein","sequence":"additional","affiliation":[{"name":"Department of Radiology, UMC Utrecht Utrecht University Utrech The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina W.","family":"Hofland","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inez","family":"Bronsveld","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marian A.","family":"Kruijswijk","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzan","family":"Schotman","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corlien W.","family":"Slingerland","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Panhuis","sequence":"additional","affiliation":[{"name":"Department of Pediatric pulmonology UMC Utrecht location Wilhelmina Childrens Hospital, Utrecht University Utrech The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. Kors","family":"van der Ent","sequence":"additional","affiliation":[{"name":"Department of Pediatric pulmonology UMC Utrecht location Wilhelmina Childrens Hospital, Utrecht University Utrech The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry G. M.","family":"Heijerman","sequence":"additional","affiliation":[{"name":"Department of Pulmonology, UMC Utrecht Utrecht University Utrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,5,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32597-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908639"},{"key":"e_1_2_9_4_1","volume-title":"Safety and Efficacy of Elexacaftor\/Tezacaftor\/Ivacaftor for \u226524 Weeks in People with CF and \u22651 F508del Allele: Interim Results of an Open\u2010Label Phase Three Clinical Trial","author":"Griese M","year":"2020"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.05.00034805"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00080312"},{"key":"e_1_2_9_7_1","first-page":"59","article-title":"Non\u2010respiratory health\u2010related quality of life in people with cystic fibrosis receiving elexacaftor\/tezacaftor\/ivacaftor","volume":"17","author":"Fajac I","year":"2022","journal-title":"J Cyst Fibros"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-1190"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03079-2020"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202011-4153OC"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.05.009"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11236900"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2022.01.012"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26318"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2022.110421"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2014.06.011"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10091999"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.resmer.2021.100829"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.26486","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T09:45:53Z","timestamp":1702028753000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.26486"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,24]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1002\/ppul.26486"],"URL":"https:\/\/doi.org\/10.1002\/ppul.26486","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,24]]},"assertion":[{"value":"2022-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-05-24","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}