{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:34:59Z","timestamp":1785803699015,"version":"3.56.0"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T00:00:00Z","timestamp":1600819200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pulm Ther"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Introduction<\/jats:title>\n<jats:p>Mutations in the cystic fibrosis transmembrane conductance regulator gene (<jats:italic>CFTR<\/jats:italic>) affect the quantity and\/or function of CFTR protein reaching the cell surface. Ivacaftor, a CFTR potentiator that enhances chloride transport, increases the channel-open probability of normal and dysfunctional CFTR. Initially approved for people with CF (pwCF) with <jats:italic>G551D-CFTR<\/jats:italic> gating mutations, ivacaftor demonstrated clinical benefit in pwCF with other gating mutations and certain residual function mutations, including <jats:italic>R117H-CFTR,<\/jats:italic> in clinical studies. We evaluated the long-term safety and efficacy of ivacaftor in pwCF aged 6\u00a0years and older with non-<jats:italic>G551D-CFTR<\/jats:italic> ivacaftor-responsive mutations.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Methods<\/jats:title>\n<jats:p>Efficacy and safety data from a phase 3, multicenter, open-label, extension study for participants from Study 110 (<jats:italic>R117H-CFTR<\/jats:italic> mutations), Study 111 (non\u2013<jats:italic>G551D-CFTR<\/jats:italic> gating mutations), and Study 113 (<jats:italic>n<\/jats:italic>-of-1 pilot study in participants with residual CFTR function) were analyzed. Following washout from the randomized parent study, participants received oral ivacaftor 150\u00a0mg once every 12\u00a0h for 104\u00a0weeks.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Forty-one of 121 participants completed treatment through 104\u00a0weeks; 59 participants who did not complete the extension study continued treatment with commercial ivacaftor. The most common adverse events were pulmonary exacerbation (46.3%) and cough (33.9%). Most treatment-emergent adverse events were mild\/moderate in severity and consistent with manifestations of CF or the ivacaftor safety profile. Rapid, durable improvement occurred across all efficacy endpoints.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Ivacaftor was generally safe and well tolerated with no new safety concerns for up to 104\u00a0weeks in pwCF with ivacaftor-responsive mutations. The pattern of improvement across efficacy endpoints was durable and generally consistent with parent-study outcomes.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Trial Registration<\/jats:title>\n<jats:p>NCT01707290<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s41030-020-00129-2","type":"journal-article","created":{"date-parts":[[2020,9,23]],"date-time":"2020-09-23T10:02:41Z","timestamp":1600855361000},"page":"303-313","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Long-Term Ivacaftor in People Aged 6 Years and Older with Cystic Fibrosis with Ivacaftor-Responsive Mutations"],"prefix":"10.1007","volume":"6","author":[{"given":"Joseph M.","family":"Pilewski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kris","family":"De Boeck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerry A.","family":"Nick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cynthia","family":"DeSouza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard B.","family":"Moss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,23]]},"reference":[{"key":"129_CR1","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","volume":"365","author":"BW Ramsey","year":"2011","unstructured":"Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365:1663\u2013722. https:\/\/doi.org\/10.1056\/NEJMoa1105185.","journal-title":"N Engl J Med"},{"key":"129_CR2","unstructured":"Kalydeco\u00ae (ivacaftor) [prescribing information]. Boston, MA: Vertex Pharmaceuticals Incorporated; 2019."},{"key":"129_CR3","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/S2213-2600(15)00545-7","volume":"4","author":"JC Davies","year":"2016","unstructured":"Davies JC, Cunningham S, Harris WT, et al. Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2\u20135 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. 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