{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:50:05Z","timestamp":1790412605982,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T00:00:00Z","timestamp":1683590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Introduction:<\/jats:bold>\n                    Recently, cystic fibrosis transmembrane regulator modulator therapy with elexacaftor\/tezacaftor\/ivacaftor has become available for children with cystic fibrosis (CF) carrying at least one\n                    <jats:italic>F508del<\/jats:italic>\n                    mutation.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Objective:<\/jats:bold>\n                    To assess the intermediate term effects of elexacaftor\/tezacaftor\/ivacaftor in children with cystic fibrosis in a real-world setting.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    We performed a retrospective analysis of records of children with cystic fibrosis, who started elexacaftor\/tezacaftor\/ivacaftor between 8\/2020 and 10\/2022. Pulmonary function tests, nutritional status, sweat chloride and laboratory data were assessed before, 3 and 6\u00a0months after the start of elexacaftor\/tezacaftor\/ivacaftor respectively.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    Elexacaftor\/tezacaftor\/ivacaftor was started in 22 children 6\u201311\u00a0years and in 24 children 12\u201317\u00a0years. Twenty-seven (59%) patients were homozygous for\n                    <jats:italic>F508del<\/jats:italic>\n                    (F\/F) and 23 (50%) patients were transitioned from ivacaftor\/lumacaftor (IVA\/LUM) or tezacaftor\/ivacaftor (TEZ\/IVA) to elexacaftor\/tezacaftor\/ivacaftor. Overall, mean sweat chloride concentration decreased by 59.3\u00a0mmol\/L (95% confidence interval: \u221265.0 to \u221253.7\u00a0mmol\/L,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.0001) under elexacaftor\/tezacaftor\/ivacaftor. Sweat chloride concentration also decreased significantly after transition from IVA\/LUM or TEZ\/IVA to elexacaftor\/tezacaftor\/ivacaftor (\u221247.8\u00a0mmol\/l; 95% confidence interval: \u221257.6 to \u221237.8\u00a0mmol\/l,\n                    <jats:italic>n<\/jats:italic>\n                    = 14,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.0001). Sweat chloride reduction was more marked in children with the F\/F than in those with the F\/MF genotype (69.4 vs 45.9\u00a0mmol\/L,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.0001). At 3\u00a0months follow-up, body-mass-index-z-score increased by 0.31 (95% CI, 0.2\u20130.42,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.0001) with no further increase at 6\u00a0months. BMI-for-age-z-score was more markedly improved in the older group. Overall pulmonary function (percent predicted FEV\n                    <jats:sub>1<\/jats:sub>\n                    ) at 3 months follow-up increased by 11.4% (95% CI: 8.0\u201314.9,\n                    <jats:italic>p<\/jats:italic>\n                    &amp;lt; 0.0001) with no further significant change after 6\u00a0months. No significant differences were noted between the age groups. Children with the F\/MF genotype had a greater benefit regarding nutritional status and pulmonary function tests than those with the F\/F genotype. Adverse events led to elexacaftor\/tezacaftor\/ivacaftor dose reduction in three cases and a temporary interruption of therapy in four cases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    In a real-world setting, elexacaftor\/tezacaftor\/ivacaftor therapy had beneficial clinical effects and a good safety profile in eligible children with cystic fibrosis comparable to previously published data from controlled clinical trials. The positive impact on pulmonary function tests and nutritional status seen after 3\u00a0months of elexacaftor\/tezacaftor\/ivacaftor therapy was sustained at 6 months follow-up.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2023.1176815","type":"journal-article","created":{"date-parts":[[2023,5,9]],"date-time":"2023-05-09T01:38:14Z","timestamp":1683596294000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Real-life impact of highly effective CFTR modulator therapy in children with cystic fibrosis"],"prefix":"10.3389","volume":"14","author":[{"given":"Margarete","family":"Olivier","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Kavvalou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Welsner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raphael","family":"Hirtz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Stra\u00dfburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivagurunathan","family":"Sutharsan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Stehling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathis","family":"Steindor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.3390\/jcm11041021","article-title":"Elexacaftor\/Tezacaftor\/Ivacaftor in Patients with Cystic Fibrosis Homozygous for the F508del Mutation and Advanced Lung Disease: A 48-Week Observational Study","volume":"11","author":"Carnovale","year":"2022","journal-title":"J. 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