{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:37:48Z","timestamp":1791333468944,"version":"4.3.1"},"reference-count":28,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp; Perspec"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The combination of Elexacaftor\/Tezacaftor\/Ivacaftor (ETI) has resulted in a significant improvement in lung function and global clinical parameters, which have not been previously achieved with other CFTR modulators. However, there is a paucity of evidence in the literature on the long\u2010term use of ETI in adolescents and patients with severe pulmonary impairment. Furthermore, the response to ETI may differ between homozygotes and heterozygotes, as well as between na\u00efve patients and those previously treated with other CFTR modulators. A retrospective study was conducted to examine changes in percent predicted forced expiratory volume in 1\u2009s (ppFEV<jats:sub>1<\/jats:sub>), body\u2010mass index (BMI), and sweat chloride concentration (SwCl) at baseline and at 6, 12 and 24\u2009months after the initiation of ETI. Secondary outcomes included the number of pulmonary exacerbations, Cystic Fibrosis Questionnaire\u2010Revised (CFQ\u2010R) score, adverse events, mortality and transplantation rates. 139 subjects were included and followed up for up to 2\u2009years after starting ETI. The results demonstrated a significant improvement in ppFEV<jats:sub>1<\/jats:sub> and BMI after 12\u2009months of therapy (respectively, 16%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; +1.5\u2009kg\/m<jats:sup>2<\/jats:sup>, <jats:italic>p<\/jats:italic>\u2009=\u20090.005), with a slight decline in the values after 24\u2009months. This effect was independent of genotype and showed a different degree of response in na\u00efve subjects compared to patients previously treated with other CFTR modulators. SwCl decreased from 84 to 37\u2009mmol\/L over 24\u2009months (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). 58.3% reduction of PEx rate was observed compared to the number of exacerbations prior to ETI. Overall, lung function, SwCl, PEx rate, CFQ\u2010R scores and BMI improved after 24\u2009months of ETI treatment. ETI was well tolerated, and none of the patients interrupted the treatment due to toxicity.<\/jats:p>","DOI":"10.1002\/prp2.70083","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T18:28:16Z","timestamp":1743791296000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Improved Clinical Outcomes With Elexacaftor\/Tezacaftor\/Ivacaftor in Patients With Cystic Fibrosis and Advanced Lung Disease: Real\u2010World Evidence From an Italian Single\u2010Center Study"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0809-5118","authenticated-orcid":false,"given":"Nicola","family":"Perrotta","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University  Rome Italy"},{"name":"Pharmacy Unit AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi Angelo","family":"Fiorito","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University  Rome Italy"},{"name":"Pharmacy Unit AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianfranco","family":"Casini","sequence":"additional","affiliation":[{"name":"Pharmacy Unit AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossella","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cV. Erspamer\u201d Sapienza University  Rome Italy"},{"name":"Pharmacy Unit AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Vescovo","sequence":"additional","affiliation":[{"name":"Pharmacy Unit AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Piciocchi","sequence":"additional","affiliation":[{"name":"Biostatistics Unit GIMEMA Foundation  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Lobello","sequence":"additional","affiliation":[{"name":"Pharmacy Unit AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Cappelli","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Poscia","sequence":"additional","affiliation":[{"name":"Clinical Research Unit AOU Policlinico Umberto I\u2010 Sapienza University  Rome Italy"},{"name":"Interdepartmental Center for Rare Diseases AOU Policlinico Umberto I\u2010 Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Cimino","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center AOU Policlinico Umberto I\u2010Sapienza University  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010016\u20102391\u2010y"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piac052"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/JEP.S255377"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)32597\u20108"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1908639"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells11111769"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16030410"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01499\u20102021"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200812\u20101845PP"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.0740"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2007.03.002"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202011\u20104153OC"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106646"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.1015"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2023.107406"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213\u20102600(21)00454\u20109"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202108\u20101986OC"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00159111"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2011.161117"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18081654"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11041021"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.03079\u20102020"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCP.0000000000001014"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2022.06.007"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26318"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2021.05.009"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2019.03.002"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ppul.26485"}],"container-title":["Pharmacology Research &amp; 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