The New Landscape of Cystic Fibrosis in the Era of Highly Effective Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy
References
- Cholon DM, Aleksandrov AA, Gentzsch M. Molecular Biology of CFTR. In: Bush A, Amaral MD, Davies JC, Simmonds NJ, Taylor-Cousar JL, Ranganathan SC, editors. Hodson and Geddes’ Cystic Fibrosis. 5th ed. Boca Raton: CRC Press; 2023:37–47. 9781003262763.
- Sands D, Walicka-Serzysko K, Doniec Z, Mastalerz-Migas A, Batura-Gabryel H, Pierzchała W. ReKOMendacje PostępowAnia w mukowiScydozie (cystic fibrosis; CF) dla lekarzy Podstawowej Opieki Zdrowotnej – KOMPAS CF – część 1,(Recommendations for the management of cystic fibrosis (CF) for primary care physicians – KOMPAS CF part 1). Pol. J. Paediatr. 2017;92(4):431–445. DOI 10.1016/j.pepo.2017.04.006
- Zolin A, Adamoli A, Zomer D, Fox A, Krasnyk M, Mayor SL, et al. Karup, Denmark: ECFS Cystic Fibrosis Patients Registry. 2024. Report No.: ISSN 3135-0798. Available from:
https://pr.ecfs.eu/annual-reports/ . - De Boeck K. Introduction: From the discovery of the CFTR gene in 1989 through to 2014. In: Bush A, Amaral MD, Davies JC, Simmonds NJ, Taylor-Cousar JL, Ranganathan SC, editors. Hodson and Geddes’ Cystic Fibrosis. 4th ed. Boca Raton: CRC Press, 2016:1–15. 9780429166976.
- De Boeck K. Cystic fibrosis in the year 2020: Adisease with a new face. Acta Paediatr. 2020;109(5):893–9. doi: 10.1111/apa.15155
- Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, et al. A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation. N Engl J Med. 2011;365(18):1663–72. doi: 10.1056/NEJMoa1105185.
- De Boeck K, Munck A, Walker S, Faro A, Hiatt P, Gilmartin G, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros. 2014 Dec;13(6):674–80. doi: 10.1016/j.jcf.2014.09.005.
- McGarry ME, Illek B, Ly NP, Zlock L, Olshansky S, Moreno C, et al. In vivo and in vitro ivacaftor response in cystic fibrosis patients with residual CFTR function: N-of-1 studies. Pediatr Pulmonol. 2017 Apr;52(4):472–9. doi: 10.1002/ppul.23659.
- Moss RB, Flume PA, Elborn JS, Cooke J, Rowe SM, McColley SA, et al. Efficacy and safety of ivacaftor in patients with cystic fibrosis who have an Arg117His-CFTR mutation: a double-blind, randomised controlled trial. Lancet Respir Med. 2015 Jul;3(7):524–33. doi: 10.1016/S2213-2600(15)00201-5.
- Davies JC, Wainwright CE, Sawicki GS, Higgins MN, Campbell D, Harris C, et al. Ivacaftor in Infants Aged 4 to <12 Months with Cystic Fibrosis and a Gating Mutation. Results of a Two-Part Phase 3 Clinical Trial. Am J Respir Crit Care Med. 2021 Mar;203(5):585–93. doi: 10.1164/rccm.202008-3177OC.
- Guimbellot JS, Baines A, Paynter A, Heltshe SL, VanDalfsen J, Jain M, et al. Long term clinical effectiveness of ivacaftor in people with the G551D CFTR mutation. J Cyst Fibros. 2021 Mar;20(2):213–9. doi: 10.1016/j.jcf.2020.11.008.
- Kawala CR, Ma X, Sykes J, Stanojevic S, Coriati A, Stephenson AL. Real-world use of ivacaftor in Canada: A retrospective analysis using the Canadian Cystic Fibrosis Registry. J Cyst Fibros. 2021 Nov;20(6):1040–5. doi: 10.1016/j.jcf.2021.03.008.
- Uluer AZ, MacGregor G, Azevedo P, Indihar V, Keating C, Mall MA, et al. Safety and efficacy of vanzacaftor-tezacaftor-deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials. Lancet Respir Med. 2023 Jun;11(6):550–62. doi: 10.1016/S2213-2600(22)00504-5.
- Wainwright CE, Elborn JS, Ramsey BW, Marigowda G, Huang X, Cipolli M, et al. Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del CFTR. N Engl J Med. 2015 Jul 16;373(3):220–31. doi: 10.1056/NEJMoa1409547.
- Hubert D, Chiron R, Camara B, Grenet D, Prévotat A, Bassinet L, et al. Real-life initiation of lumacaftor/ivacaftor combination in adults with cystic fibrosis homozygous for the Phe508del CFTR mutation and severe lung disease. J Cyst Fibros. 2017 May;16(3):388–91. doi: 10.1016/j.jcf.2017.03.003.
- Burgel PR, Durieu I, Chiron R, Mely L, Prevotat A, Murris-Espin M, et al. Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function. J Cyst Fibros. 2021 Mar;20(2):220–7. doi: 10.1016/j.jcf.2020.06.012.
- Taylor-Cousar JL, Munck A, McKone EF, van der Ent CK, Moeller A, Simard C, et al. Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis Homozygous for Phe508del. N Engl J Med. 2017 Nov 23;377(21):2013–23. doi: 10.1056/NEJMoa1709846.
- Rowe SM, Daines C, Ringshausen FC, Kerem E, Wilson J, Tullis E, et al. Tezacaftor-Ivacaftor in Residual-Function Heterozygotes with Cystic Fibrosis. N Engl J Med. 2017 Nov;377(21):2024–35. doi: 10.1056/NEJMoa1709847.
- Schwarz C, Sutharsan S, Epaud R, Klingsberg RC, Fischer R, Rowe SM, et al. Tezacaftor/ivacaftor in people with cystic fibrosis who stopped lumacaftor/ivacaftor due to respiratory adverse events. J Cyst Fibros. 2021 Mar;20(2):228–33. doi: 10.1016/j.jcf.2020.06.001.
- Keating D, Marigowda G, Burr L, Daines C, Mall MA, McKone EF, et al. VX-445-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and One or Two Phe508del Alleles. N Engl J Med. 2018 Oct;379(17):1612–20. doi: 10.1056/NEJMoa1807120.
- Middleton PG, Mall MA, Dřevínek P, Lands LC, McKone EF, Polineni D, et al. Elexacaftor-Tezacaftor-Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele. N Engl J Med. 2019 Nov;381(19):1809–19. doi: 10.1056/NEJMoa1908639.
- Heijerman HGM, McKone EF, Downey DG, Van Braeckel E, Rowe SM, Tullis E, et al. Efficacy and safety ofthe elexacaftor plus tezacaftor plus ivacaftor combination regimen in people with cystic fibrosis homozygous for the F508del mutation: a double-blind, randomised, phase 3 trial. Lancet. 2019 Nov;394(10212):1940–8. doi: 10.1016/S0140-6736(19)32597-8.
- Walicka-Serzysko K, Postek M, Mielus M, Borawska-Kowalczyk U, Milczewska J, Zybert K, et al. Comprehensive Evaluation of Elexacaftor/Tezacaftor/Ivacaftor in Paediatric Cystic Fibrosis: Nutritional, Pulmonary, and Quality-of-Life Outcomes. J Clin Med. 2025 Nov;14(22):7969. doi: 10.3390/jcm14227969.
- Keating C, Yonker LM, Vermeulen F, Prais D, Linnemann RW, Trimble A, et al. Vanzacaftor–tezacaftor–deutivacaftor versus elexacaftor–tezacaftor–ivacaftor in individuals with cystic fibrosis aged 12 years and older (SKYLINE Trials VX20-121-102 and VX20-121-103): results from two randomised, active-controlled, phase 3 trials. The Lancet Respir Med. 2025 Mar;13(3):256–71. doi: 10.1016/S2213-2600(24)00411-9.
- Hoppe JE, Kasi AS, Pittman JE, Jensen R, Thia LP, Robinson P, et al. Vanzacaftor–tezacaftor–deutivacaftor for children aged 6–11 years with cystic fibrosis (RIDGELINE Trial VX21-121-105): an analysis from a single-arm, phase 3 trial. Lancet Respir Med. 2025 Mar;13(3):244–55. doi: 10.1016/S2213-2600(24)00407-7.
- Kerem E, Orenti A, Adamoli A, Hatziagorou E, Naehrlich L, Sermet-Gaudelus I, et al. Cystic fibrosis in Europe: improved lung function and longevity - reasons for cautious optimism, but challenges remain. Eur Respir J. 2024 Mar;63(3):2301241. doi: 10.1183/13993003.01241-2023
- Cystic Fibrosis Foundation Patients Registry Highlights 2024:
https://www.cff.org/medical-professionals/2024-patient-registry-highlights . DATE ACCESS: 24.02.2026 - Burgel PR, Southern KW, Addy C, Battezzati A, Berry C, Bouchara JP, et al. Standards for the care of people with cystic fibrosis (CF); recognising and addressing CF health issues. J Cyst Fibros. 2024 Mar;23(2):187–202. doi: 10.1016/j.jcf.2024.01.005.
- Middleton PG, Simmonds NJ. Cystic fibrosis modulator therapy can reverse cystic bronchiectasis. Respirol Case Rep. 2023;11(7):e01172. doi: 10.1002/rcr2.1172.
- Hussain R, Masokano BI, Bdaiwi AS, Plummer JW, Willmering MM, Kramer EL, et al. Xe MRI Detects Ongoing Ventilation Improvements in People with Cystic Fibrosis Receiving Highly Effective Modulator Therapy. Ann Am Thorac Soc. 2026 Feb;23(2):303–307. doi: 10.1513/AnnalsATS.202505-497RL.
- Nichols DP, Morgan SJ, Skalland M, Vo AT, Van Dalfsen JM, Singh SBP, et al. Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist. J Clin Invest. 2023;133(10):e167957. doi: 10.1172/JCI167957.
- Fajac I, Burgel PR, Martin C. New drugs, new challenges in cystic fibrosis care. Eur Respir Rev. 2024 Sep;33(173): 240045. doi: 10.1183/16000617.0045-2024.
- Southern KW, Castellani C, Lammertyn E, Smyth A, VanDevanter D, Van Koningsbruggen-Rietschel S, et al. Standards of care for CFTR variant-specific therapy (including modulators) for people with cystic fibrosis. J Cyst Fibros. 2023 Jan;22(1):17–30. doi: 10.1016/j.jcf.2022.10.002.
- Southern KW, Addy C, Bell SC, Bevan A, Borawska U, Brown C, et al. Standards for the care of people with cystic fibrosis; establishing and maintaining health. J Cyst Fibros. 2024 Jan;23(1):12–28. doi: 10.1016/j.jcf.2023.12.002.
- Sermet-Gaudelus I, Orenti A, Hatziagorou E, Bakkeheim E, Naehrlich L, Kerem E, et al. Health Inequity in People with Cystic Fibrosis: Can We Close the Gap? Ann Am Thorac Soc. 2026 Feb;23(2):228–40. doi: 10.1513/AnnalsATS.202501-052OC.
- Lopez A, Daly C, Vega-Hernandez G, MacGregor G, Rubin JL. Elexacaftor/tezacaftor/ivacaftor projected survival and long-term health outcomes in people with cystic fibrosis homozygous for F508del. J Cyst Fibros. 2023 Jul ;22(4):607–14. doi: 10.1016/j.jcf.2023.02.004.
- Gramegna A, Addy C, Allen L, Bakkeheim E, Brown C, Daniels T, et al. Standards for the care of people with cystic fibrosis (CF); Planning for a longer life. J Cyst Fibros. 2024 May;23(3):375–87. doi: 10.1016/j.jcf.2024.05.007.
- Merlo CA, McGarry LJ, Thorat T, Nguyen C, DerSarkissian M, Muthukumar A, et al. Impact of age at ivacaftor initiation on pulmonary outcomes among people with cystic fibrosis. Thorax. 2024 Sept;79(10): 915-924. doi: 10.1136/thorax-2023-220559.
- Sands D, Milczewska JU, Skorupa W, Walicka-Serzysko K, Zybert K, Woźniacki Ł, et al. Standardy europejskie a sytuacja w Polsce(European standards and the situation in Poland). Pneum Pol. 2024;5(2):69–76. doi: 10.5603/pp.101627.
- Bell SC, Mall MA, Gutierrez H, Macek M, Madge S, Davies JC, et al. The future of cystic fibrosis care: a global perspective. Lancet Respir Med. 2020 Jan;8(1):65–124. doi: 10.1016/S2213-2600(19)30337-6.
DOI: https://doi.org/10.34763/jmotherandchild.20263001.d-26-00011 | Journal eISSN: 2719-535X | Journal ISSN: 2719-6488
Language: English
Page range: 180 - 186
Submitted on: Mar 9, 2026
Accepted on: May 20, 2026
Published on: Sep 25, 2026
Published by: Institute of Mother and Child
In partnership with: Paradigm Publishing Services
Publication frequency: Volume open
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© 2026 Anna Wołkowicz, Katarzyna Walicka-Serzysko, Justyna Milczewska, Dorota Sands, published by Institute of Mother and Child
This work is licensed under the Creative Commons Attribution 4.0 License.