Academic Journal
Effects of Elexacaftor/Tezacaftor/Ivacaftor on cough frequency, physical activity patterns, and sleep quality in adolescents and adults with cystic fibrosis.
| Title: | Effects of Elexacaftor/Tezacaftor/Ivacaftor on cough frequency, physical activity patterns, and sleep quality in adolescents and adults with cystic fibrosis. |
|---|---|
| Authors: | Van Braeckel E; Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium; Department of Internal Medicine and Paediatrics, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. Electronic address: Eva.VanBraeckel@UGent.be., Braun AT; University of Wisconsin School of Medicine and Public Health, Madison, WI, USA., Simmonds NJ; National Heart and Lung Institute, Imperial College London UK, Royal Brompton Hospital, part of Guy's and St Thomas' NHS Foundation Trust, London, UK., Barry PJ; Manchester University NHS Foundation Trust, Manchester, UK; Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK., Davies JC; National Heart and Lung Institute, Imperial College London UK, Royal Brompton Hospital, part of Guy's and St Thomas' NHS Foundation Trust, London, UK., Egan ME; Yale University, New Haven, CT, USA., Lapey A; Massachusetts General Hospital, Boston, MA, USA., Mall MA; Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL), associated partner site, Berlin, Germany; German Center for Child and Adolescent Health (DZKJ), partner site Berlin, Berlin, Germany; Cluster of Excellence ImmunoPreCept, Charité - Universitätsmedizin Berlin, Berlin, Germany., McKone EF; St Vincent's University Hospital, Dublin, Ireland., Peckham D; St James's University Hospital, Leeds, UK., Proesmans M; University Hospital of Leuven, Leuven, Belgium., Ramsey B; Seattle Children's Hospital, Seattle, WA, USA., Santamaria SV; Hospital Ramón y Cajal, Madrid, Spain., Smith D; The Prince Charles Hospital, Brisbane, Queensland, Australia., Taylor-Cousar JL; National Jewish Health, Denver, CO, USA., Tullis E; St Michael's Hospital, Toronto, Ontario, Canada., De Wachter E; Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium., Withers N; Royal Devon United Hospital NHS Foundation Trust, Exeter, UK., Ahluwalia N; Vertex Pharmaceuticals Incorporated, Boston, MA, USA., Conner S; Vertex Pharmaceuticals Incorporated, Boston, MA, USA., Jennings M; Vertex Pharmaceuticals Incorporated, Boston, MA, USA., Lou Y; Vertex Pharmaceuticals Incorporated, Boston, MA, USA., Weinstock TG; Vertex Pharmaceuticals Incorporated, Boston, MA, USA., Keating D; Alfred Health, and Monash University, Melbourne, Victoria, Australia. |
| Source: | Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society [J Cyst Fibros] 2026 Jul; Vol. 25 (4), pp. 682-688. Date of Electronic Publication: 2026 Mar 31. |
| Publication Type: | Journal Article; Clinical Trial, Phase IV; Clinical Trial, Phase III |
| Language: | English |
| Journal Info: | Publisher: Elsevier Country of Publication: Netherlands NLM ID: 101128966 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-5010 (Electronic) Linking ISSN: 15691993 NLM ISO Abbreviation: J Cyst Fibros Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Amsterdam ; New York : Elsevier, c2002- |
| MeSH Terms: | Cystic Fibrosis*/drug therapy , Cystic Fibrosis*/complications , Cystic Fibrosis*/physiopathology , Aminophenols*/therapeutic use , Aminophenols*/administration & dosage , Indoles*/therapeutic use , Indoles*/administration & dosage , Cough*/drug therapy , Cough*/etiology , Quinolones*/therapeutic use , Quinolones*/administration & dosage , Benzodioxoles*/therapeutic use , Benzodioxoles*/administration & dosage , Pyrrolidines*/therapeutic use , Pyrazoles*/therapeutic use , Pyrazoles*/administration & dosage , Pyridines*/therapeutic use , Pyridines*/administration & dosage , Exercise* , Sleep Quality*, Actigraphy/methods ; Chloride Channel Agonists/administration & dosage ; Chloride Channel Agonists/therapeutic use ; Humans ; Female ; Male ; Adolescent ; Adult ; Drug Combinations ; Pilot Projects ; Young Adult ; Feasibility Studies |
| Abstract: | Background: Cystic fibrosis (CF) transmembrane conductance regulator modulators improve lung function, however, effects on cough frequency, physical activity, and sleep have not been assessed in clinical studies. Methods: After a 12-week, phase 4 pilot feasibility study, we conducted a 13-week, phase 3b, open-label study in participants with CF aged ≥12 years previously naïve to elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) to assess the effects of ELX/TEZ/IVA on cough frequency, physical activity, and sleep using wearable cough monitors and actigraphy sensors (VX-445-126). Results: In study VX-445-126 (N = 81), participants treated with ELX/TEZ/IVA experienced a 91.7% reduction in cough frequency (cough events per day) (95% CI, 89.2% to 93.6%; 241.3 coughs per day at baseline to 20.3 coughs per day) from baseline at the average of week 8 through week 12 (primary endpoint). Total steps per day (secondary endpoint) increased by 638 (95% CI, 298 to 977) at the average of week 8 through week 12. Time spent above sedentary physical activity per day, time spent on moderate-to-vigorous physical activity per day, and total mean activity count per day all increased from baseline at the average of week 8 through week 12 (other efficacy endpoints). While no changes in sleep activity patterns were observed in actigraphy data, patient-reported measures of sleep quality improved (other efficacy endpoints). ELX/TEZ/IVA was generally safe and well-tolerated. Conclusions: ELX/TEZ/IVA treatment led to a > 90% reduction in daily cough frequency, with sustained improvements in physical activity and better perceptions of sleep quality. (Copyright © 2026 The Authors. Published by Elsevier B.V. All rights reserved.) |
| Competing Interests: | Declaration of competing interest EVB received fees for clinical trial leadership and participation, lectures and consultancy from Vertex Pharmaceuticals, all paid to her institution, and institutional fees for the conduct of CF clinical trials from AbbVie, Boehringer Ingelheim, and Galapagos. AB received grants from Vertex Pharmaceuticals and the Cystic Fibrosis Foundation. PJB reports speaker and consultancy fees from Vertex Pharmaceuticals. Member of DMC for Boehringer Ingelheim. EDW received institutional fees for study participation in clinical trials from Vertex Pharmaceuticals, Corbus and Ablynx. Her institution received honoraria for speaking and education activities and consultant work and for participation from Vertex Pharmaceuticals. She received support for attending travel and housing at CF-conferences by Viatris. MP received institutional fees for study participation in clinical trials from Vertex Pharmaceuticals. Her institution received honoraria for speaking and education activities and for participation in advisory boards from Vertex Pharmaceuticals. JCD has received fees from Vertex Pharmaceuticals to her university and hospital for clinical trial leadership/participation; has participated in Advisory Boards and educational/ speaking activities for Vertex Pharmaceuticals. JCD and NJS are supported by the National Institute of Health and Care Research (NIHR) through the Imperial Biomedical Research Centre, the Brompton Clinical Research Facility. JCD also has a Senior Investigator Award. NJS has participated in Advisory Boards and/or educational/speaking activities for Vertex Pharmaceuticals, Chiesi, Gilead, Teva and Boehringer Ingelheim. DP has participated in Advisory Boards and educational/speaking activities with Vertex Pharmaceuticals. JTC has received consulting fees/or has been on advisory board for Kither Biotech; has served as a DMC chair for AbbVie, received grant funding from the CF Foundation and NIH and has been an investigator on studies for 4DMT, Vertex Pharmaceuticals, Sionna, Splisense, BI, and Recode. Her institution has received funds for her advisory work from Vertex Pharmaceuticals and 4DMT. MP received institutional fees for study participation in clinical trials from Vertex Pharmaceuticals. Her institution received honoraria for participation in advisory boards from Vertex Pharmaceuticals. ET has received consulting and speaking fees from Vertex Pharmaceuticals Inc. NW has received fees from Vertex for Advisory Boards and educational/speaking activities. NA, SC, MJ, YL, and TGW are employees of Vertex Pharmaceuticals Incorporated. EM has participated in advisory boards for Vertex Pharmaceuticals and Enterprise Therapeutics, received grant funding from CF Foundation and Vertex Pharmaceuticals, and institutional fees for study participation in Vertex Pharmaceuticals clinical trials. MAM reports grants or contracts from Boehringer Ingelheim, Enterprise Therapeutics, Vertex Pharmaceuticals, German Federal Ministry of Research, Technology and Space (BMFTR) and German Research Foundation (DFG), with payments made to the institution; consulting fees from Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Splisense and Vertex Pharmaceuticals; payment or honoraria for lectures from Vertex Pharmaceuticals; travel reimbursement received for participation in advisory board meetings for Boehringer Ingelheim and Vertex Pharmaceuticals; and fees for participation on an advisory board from Boehringer Ingelheim, Enterprise Therapeutics, Kither Biotech, Pari and Vertex Pharmaceuticals. He is also an unpaid Fellow of ERS. |
| Contributed Indexing: | Keywords: Cough; Cystic fibrosis; Elexacaftor/tezacaftor/ivacaftor; Physical activity; Wearable technologies |
| Substance Nomenclature: | 0 (Aminophenols) 0 (Indoles) 0 (Drug Combinations) 0 (Quinolones) 0 (Benzodioxoles) 0 (Pyrrolidines) 0 (Pyrazoles) 0 (tezacaftor, ivacaftor drug combination) 0 (Pyridines) 0 (Chloride Channel Agonists) |
| Entry Date(s): | Date Created: 20260402 Date Completed: 20260730 Latest Revision: 20260730 |
| Update Code: | 20260731 |
| DOI: | 10.1016/j.jcf.2026.03.016 |
| PMID: | 41925449 |
| Database: | MEDLINE |
| ISSN: | 1873-5010 |
|---|---|
| DOI: | 10.1016/j.jcf.2026.03.016 |