{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T21:06:02Z","timestamp":1770498362288,"version":"3.49.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T00:00:00Z","timestamp":1718150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Cystic fibrosis transmembrane conductance regulator modulators are the only available treatment for cystic fibrosis. Although elexacaftor\/tezacaftor\/ivacaftor (ELX\/TEZ\/IVA) is well-tolerated, rash has been reported as very frequent. In severe rashes, ELX\/TEZ\/IVA withdrawal is necessary, leading to clinical deterioration. The objective of the study is to increment the experience of ELX\/TEZ\/IVA desensitization.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Adult patients who developed a delayed hypersensitivity rash to ELX\/TEZ\/IVA between December 2021 and February 2023 and required withdrawal due to ineffective rescue medication were included. Skins test for ELX\/TEZ\/IVA and IVA were conducted to establish hypersensitivity mechanism. Balijepally ELX\/TEZ\/IVA desensitization protocol was selected. In cases where desensitization had to be discontinued due to rash, an extended desensitization was proposed. Clinical and health-related quality of life parameters were collected before ELX\/TEZ\/IVA and after desensitization.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> 162 patients (81 women, 31.2 [23.8\u201342.5] years) started ELX\/TEZ\/IVA, developing rash 12 of them (7.4%, six women). Six patients (five women) required stopping ELX\/TEZ\/IVA and were selected for desensitization. Skin tests indicated delayed type-IV hypersensitivity in one patient. Two patients presented adequate tolerance to desensitization; while, four patients developed rash. Three of these patients, successfully concluded extended desensitization (one patient declined participation). No significant clinical deterioration or quality of life worsening was observed during desensitization; in fact, there was an improvement in practically all mesured parameters. All five patients who resumed ELX\/TEZ\/IVA are currently receiving therapy with good tolerance.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Desensitization to ELX\/TEZ\/IVA could be a successful and safe strategy for reintroducing this essential treatment in cases of a delayed hypersensitivity rash.<\/jats:p>","DOI":"10.3389\/fphar.2024.1392986","type":"journal-article","created":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T15:10:20Z","timestamp":1718205020000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Cystic fibrosis: desensitization in delayed hypersensitivity reactions to elexacaftor\/tezacaftor\/ivacaftor"],"prefix":"10.3389","volume":"15","author":[{"given":"L.","family":"G\u00f3mez-Ganda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Galv\u00e1n-Blasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Fern\u00e1ndez-Polo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Cardona","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Garc\u00eda-Palop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"CJ","family":"Parram\u00f3n-Teixid\u00f3","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Polverino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"\u00c1lvarez-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,12]]},"reference":[{"key":"B1","unstructured":"Data sheet of Kaftrio\u00ae (ivacaftor, tezacaftor and elexacaftor) 37.5 mg\/25 mg\/50 mg film-coated tablets (Vertex Pharmaceuticals). Spanish Agency for Medicines and Health Products (Agencia Espa\u00f1ola del Medicamento y Productos Sanitarios, AEMPS)2024"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2954","DOI":"10.1002\/ppul.26609","article-title":"Rapid desensitization to elexacaftor\/tezacaftor\/ivacaftor in a cystic fibrosis patient using fatty snack for improved absorption","volume":"58","author":"Ali","year":"2023","journal-title":"Pediatr. Pulmonol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/j.anai.2021.08.010","article-title":"Elexacaftor\/tezacaftor\/ivacaftor outpatient desensitization","volume":"128","author":"Balijepally","year":"2022","journal-title":"Ann. 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Pediatr. Pharmacol. Ther."},{"key":"B11","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1097\/FPC.0000000000000246","article-title":"PharmGKB summary: ivacaftor pathway, pharmacokinetics\/pharmacodynamics","volume":"27","author":"Fohner","year":"2017","journal-title":"Pharmacogenetic Genomics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"5882","DOI":"10.3390\/ijms21165882","article-title":"From ivacaftor to triple combination: a systematic review of efficacy and safety of CFTR modulators in people with cystic fibrosis","volume":"21","author":"Gramegna","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2546","DOI":"10.1002\/ppul.25437","article-title":"CFTR modulator drug desensitization: preserving the hope of long-term improvement","volume":"56","author":"Leonhardt","year":"2021","journal-title":"Pediatr. 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Pulmonol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1378\/chest.128.4.2347","article-title":"Development and validation of the Cystic Fibrosis Questionnaire in the United States: a health-related quality-of-life measure for cystic fibrosis","volume":"128","author":"Quittner","year":"2005","journal-title":"Chest"},{"key":"B18","doi-asserted-by":"publisher","first-page":"863280","DOI":"10.3389\/fphar.2022.863280","article-title":"Efficacy and safety of triple combination cystic fibrosis transmembrane conductance regulator modulators in patients with cystic fibrosis: a meta-analysis of randomized controlled trials","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B19","unstructured":"European cystic fibrosis society patient registry (ECFSPR) annual report 2021\n            ZolinA.\n            OrentiA.\n            JungA.\n            van RensJ.\n          2023"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1392986\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,12]],"date-time":"2024-06-12T15:10:26Z","timestamp":1718205026000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2024.1392986\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,12]]},"references-count":19,"alternative-id":["10.3389\/fphar.2024.1392986"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2024.1392986","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,12]]},"article-number":"1392986"}}