{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:43:47Z","timestamp":1790707427796,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Br J Clin Pharmacol"],"abstract":"<jats:p>Cystic fibrosis (CF) is a life\u2010threatening genetic disorder affecting approximately 160\u2009000 people worldwide. Mutations in the CF transmembrane conductance regulator (CFTR) gene cause progressive multi\u2010organ damage, particularly in the lungs. CFTR modulators have transformed CF care; however, their high costs raise concerns about cost\u2010effectiveness. This systematic review examined cost\u2010effectiveness studies of four CFTR modulators: ivacaftor (IVA), lumacaftor\u2013ivacaftor (LUM\u2010IVA), tezacaftor\u2013ivacaftor (TEZ\u2010IVA) and elexacaftor\u2013tezacaftor\u2013ivacaftor (ELX\u2010TEZ\u2010IVA). Ovid MEDLINE, Embase and government websites were searched for studies comparing modulators with standard care or each other. Study quality was assessed using the Consensus on Health Economic Criteria (CHEC) checklist and reporting quality using CHEERS 2022. A narrative synthesis was conducted and incremental cost\u2010effectiveness ratios (ICERs) were discussed. The review followed PRISMA guidelines and was registered with PROSPERO (CRD42024570006). Twenty\u2010nine studies yielded 34 ICERs (cost per quality\u2010adjusted life\u2010year [QALY] gained) across Canada, England, Ireland, Scotland, Wales and the United States. CFTR modulators produced significant clinical benefits, including improved QALYs and reduced pulmonary exacerbations, but were associated with extremely high costs, exceeding willingness\u2010to\u2010pay thresholds. IVA's ICERs ranged from US$536\u2009472\/QALY in Scotland to US$4\u2009898\u2009079\/QALY in Canada, LUM\u2010IVA's from US$378\u2009503\/QALY in Scotland to US$7\u00a0504\u2009825\/QALY in Canada, TEZ\u2010IVA's from US$635\u2009325\/QALY in Scotland to US$1\u2009657\u2009332\/QALY in the United States and ELX\u2010TEZ\u2010IVA's from US$334\u2009047\/QALY in Ireland to US$2\u2009093\u2009361\/QALY in Canada. Sensitivity analyses indicated the need for substantial price reductions to be considered cost\u2010effective. CFTR modulators provide substantial health benefits but pose significant financial challenges. Future research should broaden economic evaluations, consider societal impacts and explore strategies to improve affordability and access.<\/jats:p>","DOI":"10.1002\/bcp.70331","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T23:44:36Z","timestamp":1764114276000},"source":"Crossref","is-referenced-by-count":1,"title":["The cost\u2010effectiveness of cystic fibrosis transmembrane conductance regulator modulators: A systematic review of economic evaluations"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9039-0197","authenticated-orcid":false,"given":"Andrea Katrin","family":"Faour","sequence":"first","affiliation":[{"name":"School of Public Health Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrej","family":"Belan\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Basic and Clinical Pharmacology with Toxicology, Faculty of Medicine University of Rijeka  Rijeka Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"\u0160timac","sequence":"additional","affiliation":[{"name":"University of Rijeka  Rijeka Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1255-8653","authenticated-orcid":false,"given":"Elvira Meni Maria","family":"Gkrinia","sequence":"additional","affiliation":[{"name":"Independent researcher  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judite","family":"Goncalves","sequence":"additional","affiliation":[{"name":"Public Health Policy Evaluation Unit, School of Public Health Imperial College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Pineda","sequence":"additional","affiliation":[{"name":"The George Institute for Global Health UK, School of Public Health Imperial College London  London 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