{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:33:10Z","timestamp":1792801990013,"version":"4.5.0"},"reference-count":25,"publisher":"European Respiratory Society (ERS)","issue":"6","license":[{"start":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T00:00:00Z","timestamp":1699488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2023,9,27]]},"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In two pivotal phase 3 trials, up to 24\u2005weeks of treatment with elexacaftor\/tezacaftor\/ivacaftor (ELX\/TEZ\/IVA) was efficacious and safe in patients with cystic fibrosis (CF) \u226512\u2005years of age who have at least one\n                      <jats:italic>F508del<\/jats:italic>\n                      allele. The aim of this study is to assess long-term safety and efficacy of ELX\/TEZ\/IVA in these patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this phase 3, open-label, single-arm extension study, participants with\n                      <jats:italic>F508del<\/jats:italic>\n                      \u2013minimal function (from a 24-week parent study; n=399) or\n                      <jats:italic>F508del<\/jats:italic>\n                      \u2013\n                      <jats:italic>F508del<\/jats:italic>\n                      (from a 4-week parent study; n=107) genotypes receive ELX\/TEZ\/IVA at the same dose (ELX 200\u2005mg once daily, TEZ 100\u2005mg once daily and IVA 150\u2005mg every 12\u2005h). The primary end-point is safety and tolerability. A prespecified interim analysis was conducted when the last participant reached the Week 144 visit.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At the Week 144 interim analysis, mean duration of exposure to ELX\/TEZ\/IVA in the extension study was 151.1\u2005weeks. Exposure-adjusted rates of adverse events (AEs) (586.6 events per 100 participant-years) and serious AEs (22.4 events per 100 participant-years) were lower than in the ELX\/TEZ\/IVA treatment group in the 24-week parent study (1096.0 and 36.9 events per 100 participant-years, respectively); most participants had AEs classified as mild (16.4% of participants) or moderate (60.3% of participants) in severity. 14 participants (2.8%) had AEs that led to treatment discontinuation. Following initiation of ELX\/TEZ\/IVA, participants had increases in forced expiratory volume in 1\u2005s (FEV\n                      <jats:sub>1<\/jats:sub>\n                      ) percentage predicted, Cystic Fibrosis Questionnaire-Revised respiratory domain score and body mass index, and had decreases in sweat chloride concentration and pulmonary exacerbation rates that were maintained over the interim analysis period. The mean annualised rate of change in FEV\n                      <jats:sub>1<\/jats:sub>\n                      % pred was +0.07 (95% CI \u22120.12\u20130.26) percentage points among the participants.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ELX\/TEZ\/IVA was generally safe and well tolerated, with a safety profile consistent with the 24-week parent study. Participants had sustained improvements in lung function, respiratory symptoms, CF transmembrane conductance regulator function, pulmonary exacerbation rates and nutritional status. These results support the favourable safety profile and durable, disease-modifying clinical benefits of ELX\/TEZ\/IVA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1183\/13993003.02029-2022","type":"journal-article","created":{"date-parts":[[2023,11,9]],"date-time":"2023-11-09T10:45:42Z","timestamp":1699526742000},"page":"2202029","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":108,"title":["Long-term safety and efficacy of elexacaftor\/tezacaftor\/ivacaftor in people with cystic fibrosis and at least one\n                    <i>F508del<\/i>\n                    allele: 144-week interim results from a 192-week open-label extension study"],"prefix":"10.1183","volume":"62","author":[{"given":"Cori L.","family":"Daines","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Tullis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6839-0936","authenticated-orcid":false,"given":"Rachel W.","family":"Linnemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4057-2199","authenticated-orcid":false,"given":"Marcus A.","family":"Mall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward F.","family":"McKone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepika","family":"Polineni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradley S.","family":"Quon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9084-4968","authenticated-orcid":false,"given":"Felix C.","family":"Ringshausen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Rowe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiran","family":"Selvadurai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5436-9722","authenticated-orcid":false,"given":"Jennifer L.","family":"Taylor-Cousar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Withers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Ahluwalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel M.","family":"Moskowitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentin","family":"Prieto-Centurion","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyuan Vincent","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya","family":"Weinstock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjuan","family":"Xuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaohua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Ramsey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0113-912X","authenticated-orcid":false,"given":"Matthias","family":"Griese","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2023,11,9]]},"reference":[{"key":"2024102103194367000_62.6.2202029.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60327-5"},{"key":"2024102103194367000_62.6.2202029.2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)00576-6"},{"key":"2024102103194367000_62.6.2202029.3","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: a global perspective","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet Respir Med"},{"key":"2024102103194367000_62.6.2202029.4","unstructured":"Cystic Fibrosis Foundation . 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