Academic Journal
Elexacaftor/tezacaftor/ivacaftor is safe and effectively reduces sino-nasal symptoms in people with cystic fibrosis post lung transplantation.
| Τίτλος: | Elexacaftor/tezacaftor/ivacaftor is safe and effectively reduces sino-nasal symptoms in people with cystic fibrosis post lung transplantation. |
|---|---|
| Συγγραφείς: | Mathiesen IHM; Adult Cystic Fibrosis Center, Dept. of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark., Rönsholt FF; Dept. of Cardiology, Section for Lung Transplantation, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: froe0010@regionh.dk., Aanæs K; Dept. of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark., Bille J; Dept. of Otorhinolaryngology, Head and Neck Surgery, Aarhus University Hospital, Denmark., von Buchwald C; Dept. of Otorhinolaryngology, Head and Neck Surgery and Audiology, Copenhagen University Hospital, Rigshospitalet, Denmark; Dept. of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Jensen-Fangel S; Adult Cystic Fibrosis Center, Dept. of Infectious Diseases, Aarhus University Hospital, Denmark; Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark., Qvist T; Adult Cystic Fibrosis Center, Dept. of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark., Katzenstein TL; Adult Cystic Fibrosis Center, Dept. of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark., Bendstrup E; Center for Rare Lung Diseases, Aarhus University Hospital, Denmark; Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark., Perch M; Dept. of Cardiology, Section for Lung Transplantation, Copenhagen University Hospital, Rigshospitalet, Denmark; Dept. of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Jeppesen M; Adult Cystic Fibrosis Center, Dept. of Infectious Diseases, Aarhus University Hospital, Denmark; Dept. of Clinical Medicine, Aarhus University, Aarhus, Denmark. |
| Πηγή: | Respiratory medicine [Respir Med] 2026 Jun; Vol. 257, pp. 108807. Date of Electronic Publication: 2026 Apr 02. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: England NLM ID: 8908438 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-3064 (Electronic) Linking ISSN: 09546111 NLM ISO Abbreviation: Respir Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2003- : Oxford : Elsevier Original Publication: London : Baillière Tindall, in association with the British Thoracic Society, [c1989- |
| Ιατρικοί όροι (MeSH): | Cystic Fibrosis*/surgery , Cystic Fibrosis*/complications , Cystic Fibrosis*/drug therapy , Lung Transplantation*/adverse effects , Aminophenols*/therapeutic use , Aminophenols*/adverse effects , Aminophenols*/administration & dosage , Indoles*/therapeutic use , Indoles*/adverse effects , Indoles*/administration & dosage , Benzodioxoles*/therapeutic use , Benzodioxoles*/adverse effects , Benzodioxoles*/administration & dosage , Quinolones*/therapeutic use , Quinolones*/adverse effects , Quinolones*/administration & dosage , Pyridines*/therapeutic use , Pyridines*/adverse effects , Pyridines*/administration & dosage , Pyrazoles*/therapeutic use , Pyrazoles*/adverse effects , Pyrrolidines*/therapeutic use, Immunosuppressive Agents/therapeutic use ; Calcineurin Inhibitors/therapeutic use ; Chloride Channel Agonists/therapeutic use ; Humans ; Female ; Male ; Adult ; Middle Aged ; Drug Combinations ; Treatment Outcome ; Young Adult ; Adolescent ; Denmark ; Quinolines |
| Περίληψη: | Background/aim: This investigator-initiated, open-labelled study describes safety and extrapulmonary outcomes of elexacaftor/tezacaftor/ivacaftor (ETI) treatment in people with cystic fibrosis after lung transplantation (pwCF + LTX), with particular focus on sino-nasal symptoms. ETI has not been systematically administered to people with cystic fibrosis after lunge transplantation (pwCF + LTX) due to lack of data from this subgroup and concerns about potential interactions with immunosuppressive therapy. Methods: All pwCF + LTX in Denmark were screened for eligibility and included participants were treated with ETI in standard dosages for 24 weeks, with examinations before and after ETI initiation. Eligibility criteria were at least one F508del mutation, estimated glomerular filtration rate (eGFR) above 30 ml/min/1,73m2, ≤Child-Pugh class B, did not already receive ETI, contraception usage for women, life expectancy exceeding study duration, and considered able to adhere to safety protocol. Safety was determined by calcineurin inhibitor (CNI) trough levels, biochemical markers of organ failure, adverse events, and hospital admissions. Examinations included blood samples (including trough levels of immunosuppressants), Sino-nasal Outcome Test 22 (SNOT-22), smell test, nasal endoscopy score and sinus CT scan, sweat test and spirometry. Results: Of the 36 pwCF + LTX screened, 24 were eligible and 17 accepted to participate. Five participants ended ETI treatment before study completion because of side effects, most commonly dizziness, flu-like symptoms, sleep problems, and gastrointestinal symptoms. The study showed striking effects on sino-nasal symptoms based on a significantly reduced sinonasal symptom score (SNOT-22) and CT scores; further, the ability to smell improved objectively and nasal endoscopy showed reductions in polyp size, edema and discharge. No effects were found on weight, HbA1C, and FEV1 % predicted. Most participants required reduction in CNI dose, but management of immunosuppression was uncomplicated. Conclusion: ETI has a dramatic effect on sino-nasal symptoms and can safely be co-administered with CNI with careful monitoring of trough levels. (Copyright © 2026 The Authors. Published by Elsevier Ltd.. All rights reserved.) |
| Competing Interests: | Declaration of competing interest TQ and MJ have received research grants from Vertex Pharmaceuticals outside the submitted work. Funding was given to the researchers’ institutions. None of the remaining authors have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work. Examples of potential conflicts of interest include employment, consultancies, stock ownership, honoraria, paid expert testimony, patent applications/registrations, and grants or other funding. |
| Substance Nomenclature: | 0 (Aminophenols) 0 (Indoles) 0 (Benzodioxoles) 0 (Quinolones) 0 (Drug Combinations) 0 (Pyridines) 0 (Immunosuppressive Agents) 0 (Pyrazoles) 0 (elexacaftor, ivacaftor, tezacaftor drug combination) 0 (Calcineurin Inhibitors) 0 (Pyrrolidines) 0 (Chloride Channel Agonists) 0 (Quinolines) |
| Entry Date(s): | Date Created: 20260405 Date Completed: 20260714 Latest Revision: 20260714 |
| Update Code: | 20260715 |
| DOI: | 10.1016/j.rmed.2026.108807 |
| PMID: | 41935701 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1532-3064 |
|---|---|
| DOI: | 10.1016/j.rmed.2026.108807 |