{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:26:03Z","timestamp":1775348763789,"version":"3.50.1"},"reference-count":20,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"unspecified","delay-in-days":28,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Resp Res"],"accepted":{"date-parts":[[2024,6,24]]},"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Ivacaftor approval was extended to people with cystic fibrosis (CF) with \u22651 of 28 additional ivacaftor-responsive mutations in the USA in 2017 based on preclinical in vitro data. This retrospective, observational study assessed real-world clinical response to ivacaftor in people with CF with \u22651 of these mutations, using data from the US Cystic Fibrosis Foundation Patient Registry.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Participants aged \u22652 years with \u22651 of 28 eligible mutations initiating ivacaftor between May 2017 and December 2018 were included. Clinical outcomes data were evaluated for \u22641 year before and \u22642 years after ivacaftor initiation. Participants initiating ivacaftor between May and December 2017 (2017 cohort) were used for the primary analysis because up to 2 years of post-ivacaftor-initiation data were available. Analyses were descriptive; key outcomes included percent predicted forced expiratory volume in 1 s (ppFEV<jats:sub>1<\/jats:sub>), body mass index (BMI) and BMI z-score, pulmonary exacerbations (PEx) and hospitalisations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The study included 1004 eligible participants. In the 2017 cohort (n=613), mean absolute change in ppFEV<jats:sub>1<\/jats:sub> from pre-ivacaftor initiation was 1.9 (95% CI 1.4, 2.4) and 1.8 (95% CI 1.0, 2.7) percentage points in years 1 and 2 post-ivacaftor initiation, respectively; mean absolute change in BMI was 0.6 (95% CI 0.5, 0.7) and 1.0 (95% CI 0.8, 1.2) kg\/m<jats:sup>2<\/jats:sup> in years 1 and 2, respectively; BMI z-score was unchanged. Annualised event rates of PEx and hospitalisations per patient-year were lower with ivacaftor (0.24 (95% CI 0.21, 0.26) and 0.28 (95% CI 0.25, 0.31), respectively) compared with pre-ivacaftor initiation (0.41 (95% CI 0.37, 0.46) and 0.45 (95% CI 0.41, 0.49), respectively).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These real-world observational study findings support the effectiveness of ivacaftor in people with CF aged \u22652 years with selected <jats:italic>CFTR<\/jats:italic> mutations.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjresp-2023-002033","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T14:21:29Z","timestamp":1722262889000},"page":"e002033","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Real-world impact of ivacaftor in people with cystic fibrosis and select ivacaftor-responsive mutations"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5768-4237","authenticated-orcid":false,"given":"Craig","family":"McKinnon","sequence":"first","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teja","family":"Thorat","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Craft","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Higgins","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals (Europe) Limited, London, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"key":"2025083109494919000_11.1.e002033.1","unstructured":"Cystic Fibrosis Foundation . What is CF? About cystic fibrosis. Available: https:\/\/www.cff.org\/What-is-CF\/About-Cystic-Fibrosis\/ [Accessed 9 Nov 2021]."},{"key":"2025083109494919000_11.1.e002033.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2772657"},{"key":"2025083109494919000_11.1.e002033.3","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":"2025083109494919000_11.1.e002033.4","doi-asserted-by":"crossref","first-page":"193","DOI":"10.4103\/jpgm.JPGM_263_18","article-title":"Cystic fibrosis revisited","volume":"65","author":"Kulkarni","year":"2019","journal-title":"J Postgrad Med"},{"key":"2025083109494919000_11.1.e002033.5","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-020-67729-5","article-title":"Altered iron metabolism in cystic fibrosis macrophages: the impact of CFTR modulators and implications for pseudomonas aeruginosa survival","volume":"10","author":"Hazlett","year":"2020","journal-title":"Sci Rep"},{"key":"2025083109494919000_11.1.e002033.6","unstructured":"Vertex Pharmaceuticals Incorporated . KALYDECO\u00ae (Ivacaftor). Highlights of prescribing information. 2014. Available: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2014\/203188s014lbl.pdf [Accessed 8 Mar 2022]."},{"key":"2025083109494919000_11.1.e002033.7","unstructured":"Vertex Pharmaceuticals Incorporated . KALYDECO\u00ae (Ivacaftor). Highlights of prescribing information. 2017. Available: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/203188s019lbl.pdf [Accessed 8 Mar 2022]."},{"key":"2025083109494919000_11.1.e002033.8","unstructured":"Vertex Pharmaceuticals Incorporated . KALYDECO\u00ae (Ivacaftor). Highlights of prescribing information. 2023. Available: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2023\/207925s016lbl.pdf [Accessed 24 Aug 2023]."},{"key":"2025083109494919000_11.1.e002033.9","article-title":"Clinical characteristics and disease burden in patients with cystic fibrosis with residual function mutations in the US cystic fibrosis foundation patient registry","volume":"201","author":"Le Camus","year":"2020","journal-title":"Am J Respir Crit Care Med"},{"key":"2025083109494919000_11.1.e002033.10","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.201511-781OC"},{"key":"2025083109494919000_11.1.e002033.11","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00080312"},{"key":"2025083109494919000_11.1.e002033.12","unstructured":"Centers for Disease Control and Prevention . CDC growth charts: (1). 2016. Available: https:\/\/www.cdc.gov\/growthcharts\/cdc_charts.htm [Accessed 12 Jan 2022]."},{"key":"2025083109494919000_11.1.e002033.13","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2017-210394"},{"key":"2025083109494919000_11.1.e002033.14","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1007\/s41030-021-00158-5","article-title":"Real-world long-term ivacaftor for cystic fibrosis in France: clinical effectiveness and healthcare resource utilization","volume":"7","author":"Hubert","year":"2021","journal-title":"Pulm Ther"},{"key":"2025083109494919000_11.1.e002033.15","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.jcf.2019.05.015","article-title":"Disease progression in patients with cystic fibrosis treated with ivacaftor: data from national US and UK registries","volume":"19","author":"Volkova","year":"2020","journal-title":"J Cyst Fibros"},{"key":"2025083109494919000_11.1.e002033.16","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1007\/s41030-020-00115-8","article-title":"Real-world outcomes among patients with cystic fibrosis treated with ivacaftor: 2012\u20132016 experience","volume":"6","author":"Higgins","year":"2020","journal-title":"Pulm Ther"},{"key":"2025083109494919000_11.1.e002033.17","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1164\/rccm.201608-1678LE","article-title":"Patients with cystic fibrosis and a G551D or homozygous F508del mutation: similar lung function decline","volume":"195","author":"Sawicki","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2025083109494919000_11.1.e002033.18","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.jcf.2022.12.009","article-title":"Effect of elexacaftor\/tezacaftor\/ivacaftor on annual rate of lung function decline in people with cystic fibrosis","volume":"22","author":"Lee","year":"2023","journal-title":"J Cyst Fibros"},{"key":"2025083109494919000_11.1.e002033.19","doi-asserted-by":"publisher","DOI":"10.1093\/qjmed\/hcp120"},{"key":"2025083109494919000_11.1.e002033.20","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1513\/AnnalsATS.202006-659OC","article-title":"Ivacaftor in people with cystic fibrosis and a 3849+10KB C\u2192T or D1152H residual function mutation","volume":"18","author":"Kerem","year":"2021","journal-title":"Ann Am Thorac Soc"}],"container-title":["BMJ Open Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjresp-2023-002033","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,31]],"date-time":"2025-08-31T16:49:59Z","timestamp":1756658999000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopenrespres.bmj.com\/lookup\/doi\/10.1136\/bmjresp-2023-002033"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7]]},"references-count":20,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,7,29]]},"published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1136\/bmjresp-2023-002033"],"URL":"https:\/\/doi.org\/10.1136\/bmjresp-2023-002033","relation":{},"ISSN":["2052-4439"],"issn-type":[{"value":"2052-4439","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7]]}}}