{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T23:50:47Z","timestamp":1782258647947,"version":"3.54.5"},"reference-count":18,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T00:00:00Z","timestamp":1669593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Elexacaftor\/tezacaftor\/ivacaftor (ETI) is a cystic fibrosis (CF) transmembrane conductance regulator modulator, which has shown efficacy in CF patients (\u22656\u2009years) with \u22651 Phe508del mutation and a minimal function mutation. In October 2019, ETI became available on compassionate use basis for Dutch CF patients with severe lung disease. Our objective was to investigate safety and efficacy of ETI in this patient group in a real\u2010life setting. A multicenter longitudinal observational study was conducted to examine changes in FEV<jats:sub>1<\/jats:sub>, BMI, and adverse events at initiation and 1, 3, 6, and 12\u2009months after starting ETI. The number of exacerbations was recorded in the 12\u2009months before and the 12\u2009months after ETI treatment. Patients eligible for compassionate use had a FEV<jats:sub>1<\/jats:sub> &lt;40% predicted. Wilcoxon signed\u2010rank test analyzed changes over time. Twenty subjects were included and followed up for up to 12\u2009months after starting ETI. Treatment was well tolerated with mild side effects reported, namely, rash (15%) and stomach ache (20%) with 80% resolving within 1\u00a0month. Mean absolute increase of FEV<jats:sub>1<\/jats:sub> was 11.8\/13.7% (<jats:italic>p<\/jats:italic>\u00a0\u2264\u2009.001) and BMI was 0.49\/1.87\u2009kg\/m<jats:sup>2<\/jats:sup> (<jats:italic>p<\/jats:italic>\u00a0&lt;\u2009.001\u20130.02) after 1\/12\u2009months, respectively. In comparison to the number of exacerbations pretrial, there was a marked reduction in exacerbations after initiation. Our findings show long\u2010term effects of treatment with ETI in patients with severe CF lung disease in a real\u2010life setting. Treatment with ETI is associated with increased lung function and BMI, less exacerbations, and only mild side effects.<\/jats:p>","DOI":"10.1002\/prp2.1015","type":"journal-article","created":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T11:24:02Z","timestamp":1669634642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Real\u2010life efficacy and safety of elexacaftor\/tezacaftor\/ivacaftor on severe cystic fibrosis lung disease patients"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9895-9636","authenticated-orcid":false,"given":"Renate","family":"Kos","sequence":"first","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne H.","family":"Neerincx","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic W.","family":"Fenn","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"},{"name":"Laboratory of Experimental Intensive Care and Anaesthesiology Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Brinkman","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rianne","family":"Lub","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffie E. M.","family":"Vonk","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jolt","family":"Roukema","sequence":"additional","affiliation":[{"name":"Department of Paediatric Pulmonology, Amalia Children's Hospital Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique H.","family":"Reijers","sequence":"additional","affiliation":[{"name":"Department of Pulmonology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne W. J.","family":"Terheggen\u2010Lagro","sequence":"additional","affiliation":[{"name":"Department Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital Amsterdam University Medical Centres  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josje","family":"Altenburg","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christof J.","family":"Majoor","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieuwe D.","family":"Bos","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"},{"name":"Department of Intensive Care Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric G.","family":"Haarman","sequence":"additional","affiliation":[{"name":"Department Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital Amsterdam University Medical Centres  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke H.","family":"Maitland\u2010van der Zee","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine Amsterdam University Medical Centres \u2013 loc. AMC  Amsterdam The Netherlands"},{"name":"Department Paediatric Respiratory Medicine and Allergy, Emma Children's Hospital Amsterdam University Medical Centres  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Amsterdam Mucociliary Clearance Disease (AMCD) Research Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(90)90148-8"},{"key":"e_1_2_10_3_1","unstructured":"Cystic Fibrosis Foundation Patient Registry 2019 Annual Data Report Bethesda Maryland Maryland.2020.https:\/\/www.cff.org\/Research\/Researcher\u2010Resources\/Patient\u2010Registry\/2019\u2010Patient\u2010Registry\u2010Annual\u2010Data\u2010Report.pdf"},{"key":"e_1_2_10_4_1","unstructured":"Nederlandse CF Registratie 2020. 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