Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Pulmonary Outcomes
3.1.1. Ivacaftor (IVA)
3.1.2. Lumacaftor/Ivacaftor (LUM/IVA)
3.1.3. Elexacaftor/Tezacaftor/Ivacaftor (ETI)
3.2. Microbiology and Infection
3.2.1. IVA
3.2.2. ETI
3.2.3. Multiple Modulators
3.3. Gastrointestinal and Nutritional Outcomes
3.3.1. IVA
3.3.2. ETI
3.3.3. Multiple Modulators
3.4. Cystic Fibrosis-Related Diabetes (CFRD)
ETI
3.5. Laboratory Parameters
IVA and LUM/IVA
3.6. Healthcare Resource Utilization
3.6.1. IVA
3.6.2. ETI
3.7. Fertility and Pregnancy
Multiple Modulators
3.8. Quality of Life
ETI
3.9. Adverse Events
ETI
3.10. Epidemiology and Access
3.10.1. IVA
3.10.2. LUM/IVA
3.10.3. ETI
3.10.4. Multiple Modulators
3.11. Multiple Clinical Outcomes
3.11.1. IVA
3.11.2. LUM/IVA
3.11.3. ETI
3.11.4. Multiple Modulators
TOPIC | Year | Registry | CFTR Modulator | Outcomes | Reference Number |
---|---|---|---|---|---|
Adverse events | 2024 | GER, US | ETI | Mental health | [33] |
CF-related diabetes | 2024 | DK | ETI | HbA1c, CGM | [24] |
Epidemiology and access | 2018 | US | LUM/IVA | Prescription of LUM/IVA | [35] |
2019 | US | LUM/IVA | Simulation model, survival, survival projection | [36] | |
2020 | TUR | All | Allelic frequencies | [43] | |
2021 | CAN | ETI | Forecasting, microsimulation | [39] | |
2022 | Various | ETI | Diagnosed subjects, projections | [45] | |
2023 | UK | ETI | Survival | [40] | |
2023 | US | ETI | Survival, mortality | [34] | |
2023 | WAL | ETI | Hospitalizations | [41] | |
2024 | RU | All | Genetic variants | [48] | |
2024 | EU | All | FEV1, Gross National Income | [47] | |
2024 | Various | All | Prevalence, Gross domestic product | [46] | |
2024 | RU | LUM/IVA | Sweat chloride, FVC, ADR | [37] | |
2024 | SWE | LUM/IVA | Visits, costs, FEV1 | [38] | |
2025 | US | ETI | Prescriptions, FEV1, ethnicity | [42] | |
2025 | US | All | Age, ethnicity, FEV1, prescriptions | [44] | |
2025 | TUR | All | CFTR variants | [49] | |
Gastrointestinal | 2022 | US | All | BMI | [22] |
2023 | UK | ETI | BMI, energy intake | [21] | |
2024 | US, UK | IVA | PERT | [20] | |
2024 | US | All | BMI, Growth | [23] | |
Healthcare resource utilization | 2019 | IRL | IVA | Antibiotic cycles, hospitalizations, FEV1 | [26] |
2022 | UK | IVA | Burden of illness | [27] | |
2022 | UK | ETI | Burden of illness | [28] | |
2025 | DK | ETI | Hospitalizations | [29] | |
2025 | DK | ETI | Burden of illness | [30] | |
Imaging | 2022 | FRA | LUM/IVA | CT | [8] |
Laboratory parameters | 2019 | US | IVA, LUM/IVA | Hgb levels | [25] |
Microbiology | 2024 | GER | ETI | Culture positivity | [17] |
2019 | UK | IVA | Culture positivity | [15] | |
2025 | UK | IVA | ABPA predictors | [16] | |
2025 | EU | ETI | Culture positivity | [18] | |
2025 | US | IVA, LUM/IVA | Culture positivity, treatments | [19] | |
Multiple clinical outcomes | 2015 | US | IVA | BMI, growth, FEV1 | [50] |
2018 | US | IVA | Hospitalizations, complications, FEV1, microbiology | [51] | |
2020 | US, UK | IVA | Hospitalizations, complications, FEV1, microbiology | [52] | |
2020 | US, UK | IVA | Hospitalizations, risks of death, transplant, PEx | [53] | |
2020 | FRA | LUM/IVA | FEV1, PEx, BMI | [57] | |
2021 | CAN | IVA | FEV1, PEx, BMI | [54] | |
2021 | ITA | IVA | FEV1, PEx, BMI | [55] | |
2021 | FRA | ETI | FEV1, PEx, BMI, treatments | [58] | |
2023 | US | ETI | PEx, hospitalizations, microbiology, BMI, FEV1 | [59] | |
2023 | RU | ETI, LUM/IVA | FEV1, BMI | [60] | |
2024 | EU | LUM/IVA | Growth, PEx, Hospitalizations | [56] | |
Pregnancy | 2017 | US | IVA, LUM/IVA | Pregnancy rates and outcomes | [31] |
Pulmonology | 2018 | FRA | IVA | FEV1, microbiology, treatments | [4] |
2021 | FRA | LUM/IVA | FEV1, BMI, treatments | [7] | |
2022 | FRA | ETI | Rate of transplants, burden of illness | [11] | |
2022 | FRA | LUM/IVA | LCI, FEV1 | [9] | |
2024 | DK | ETI | FEV1, FVC | [12] | |
2024 | DK | ETI | FEV1, BMI, oxygen uptake | [14] | |
2024 | US | IVA | FEV1 | [5] | |
2024 | US | ETI | FEV1, PEx | [13] | |
2025 | NL | LUM/IVA | FEV1, LCI, CT scan, sweat chloride | [10] | |
2025 | US | IVA | FEV1 variability | [6] | |
Quality of life | 2021 | FRA | ETI | Treatment burden | [32] |
4. Discussion
5. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ABPA | Allergic |
BA | Broncho-alveolar |
BMI | Body mass index |
CGM | Continuous glucose monitoring |
CF | Cystic Fibrosis |
CFRD | Cystic Fibrosis-related diabetes |
CFTR | Cystic Fibrosis transmembrane conductance regulator |
CFTRm | CFTR Modulator(s) |
CT | Computed Tomography |
ECFSPR | European Cystic Fibrosis Society Patient Registry |
ETI | Elexacaftor/Tezacaftor/Ivacaftor |
HbA1c | Hemoglobin A1c |
IVA | Ivacaftor |
LCI | Lung Clearance Index |
LUM | Lumacaftor |
MeSH | Medical Subject Headings |
Pa | Pseudomonas aeruginosa |
PERT | Pancreatic enzyme replacement therapy |
PEx | Pulmonary Exacerbations |
ppFEV1 | percent predicted forced expiratory volume in one second |
RCT | Randomized controlled trials |
References
- Grasemann, H.; Ratjen, F. Cystic Fibrosis. N. Engl. J. Med. 2023, 389, 1693–1707. [Google Scholar] [CrossRef] [PubMed]
- Mall, M.A.; Brugha, R.; Gartner, S.; Legg, J.; Moeller, A.; Mondejar-Lopez, P.; Prais, D.; Pressler, T.; Ratjen, F.; Reix, P.; et al. Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Children 6 Through 11 Years of Age with Cystic Fibrosis Heterozygous for. Am. J. Respir. Crit. Care Med. 2022, 206, 1361–1369. [Google Scholar] [CrossRef]
- Jackson, A.D.; Goss, C.H. Epidemiology of CF: How registries can be used to advance our understanding of the CF population. J. Cyst. Fibros. 2018, 17, 297–305. [Google Scholar] [CrossRef]
- Hubert, D.; Dehillotte, C.; Munck, A.; David, V.; Baek, J.; Mely, L.; Dominique, S.; Ramel, S.; Danner Boucher, I.; Lefeuvre, S.; et al. Retrospective observational study of French patients with cystic fibrosis and a Gly551Asp-CFTR mutation after 1 and 2years of treatment with ivacaftor in a real-world setting. J. Cyst. Fibros. 2018, 17, 89–95. [Google Scholar] [CrossRef] [PubMed]
- Merlo, C.; Thorat, T.; McGarry, L.J.; Scirica, C.V.; DerSarkissian, M.; Nguyen, C.; Gu, Y.M.; Muthukumar, A.; Healy, J.; Rubin, J.L.; et al. A Retrospective, Longitudinal Registry Study on the Long-Term Durability of Ivacaftor Treatment in People with Cystic Fibrosis. Pulm. Ther. 2024, 10, 483–494. [Google Scholar] [CrossRef]
- Szczesniak, R.D.; Andrinopoulou, E.R.; Li, H.; Jain, R.; Mayer-Hamblett, N.; Ostrenga, J.; Palipana, A.K.; Pasta, D.J.; Rosenfeld, M.; Todd, J.; et al. Real-world association between ivacaftor initiation and lung function variability: A registry study. J. Cyst. Fibros. 2025, in press. [CrossRef]
- Burgel, P.R.; Durieu, I.; Chiron, R.; Mely, L.; Prevotat, A.; Murris-Espin, M.; Porzio, M.; Abely, M.; Reix, P.; Marguet, C.; et al. Clinical response to lumacaftor-ivacaftor in patients with cystic fibrosis according to baseline lung function. J. Cyst. Fibros. 2021, 20, 220–227. [Google Scholar] [CrossRef] [PubMed]
- Campredon, A.; Battistella, E.; Martin, C.; Durieu, I.; Mely, L.; Marguet, C.; Belleguic, C.; Murris-Espin, M.; Chiron, R.; Fanton, A.; et al. Using chest computed tomography and unsupervised machine learning for predicting and evaluating response to lumacaftor-ivacaftor in people with cystic fibrosis. Eur. Respir. J. 2022, 59, 2101344. [Google Scholar]
- Reix, P.; Tatopoulos, A.; Ioan, I.; Le Bourgeois, M.; Bui, S.; Choukroun, M.L.; Bessaci-Kabouya, K.; Gerardin, M.; Bokov, P.; Da Silva, J.; et al. Real-world assessment of LCI following lumacaftor-ivacaftor initiation in adolescents and adults with cystic fibrosis. J. Cyst. Fibros. 2022, 21, 155–159. [Google Scholar] [CrossRef]
- Zwitserloot, A.M.; Aziz, S.Z.; Chen, Y.; Bannier, M.A.G.E.; Janssens, H.M.; Merkus, P.F.J.M.; Nuijsink, M.; Terheggen-Lagro, S.W.J.; Tiddens, H.A.W.M.; Zomer-van Ommen, D.D.; et al. Introduction of Ivacaftor/Lumacaftor in Children With Cystic Fibrosis Homozygous for F508del in the Netherlands: A Nationwide Real-Life Study. Pediatr. Pulmonol. 2025, 60, e27473. [Google Scholar] [CrossRef]
- Martin, C.; Reynaud-Gaubert, M.; Hamidfar, R.; Durieu, I.; Murris-Espin, M.; Danner-Boucher, I.; Chiron, R.; Leroy, S.; Douvry, B.; Grenet, D.; et al. Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis. J. Cyst. Fibros. 2022, 21, 489–496. [Google Scholar] [CrossRef]
- Leo-Hansen, C.; Faurholt-Jepsen, D.; Qvist, T.; Højte, C.; Nielsen, B.U.; Bryrup, T.; Henriksen, E.H.; Katzenstein, T.; Skov, M.; Mathiesen, I.H.M.; et al. Lung function improvement on triple modulators: High-resolution, nationwide data from the Danish Cystic Fibrosis Cohort. ERJ Open Res. 2024, 10, 00339–02024. [Google Scholar] [CrossRef] [PubMed]
- Cromwell, E.A.; Ostrenga, J.S.; Sanders, D.B.; Morgan, W.; Castellani, C.; Szczesniak, R.; Burgel, P.R. Impact of the expanded label for elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis with no F508del variant in the USA. Eur. Respir. J. 2024, 64, 2401146. [Google Scholar] [CrossRef]
- Philipsen, L.K.D.; Olesen, H.V.; Jensen, J.H.; Olsen, M.F.; Faurholt-Jepsen, D.; Buchvald, F.; Nielsen, K.G.; Skov, M.; Pressler, T. Changes in exercise capacity in people with Cystic Fibrosis after one year of Elexacaftor/Tezacaftor/Ivacaftor treatment—A Danish prospective cohort. J. Cyst. Fibros. 2024, 23, 1080–1086. [Google Scholar] [CrossRef] [PubMed]
- Frost, F.J.; Nazareth, D.S.; Charman, S.C.; Winstanley, C.; Walshaw, M.J. Ivacaftor Is Associated with Reduced Lung Infection by Key Cystic Fibrosis Pathogens. A Cohort Study Using National Registry Data. Ann. Am. Thorac. Soc. 2019, 16, 1375–1382. [Google Scholar] [CrossRef]
- Chesshyre, E.L.D.; Enderby, B.; Shore, A.C.; Warren, F.C.; Warris, A. Longitudinal Study on Clinical Predictors for Allergic Bronchopulmonary Aspergillosis in Children and Young People with Cystic Fibrosis Highlights the Impact of Infection with Aspergillus and Pseudomonas and Ivacaftor Treatment. J. Fungi 2025, 11, 116. [Google Scholar] [CrossRef] [PubMed]
- Dittrich, A.M.; Sieber, S.; Naehrlich, L.; Burkhart, M.; Hafkemeyer, S.; Tümmler, B.; Registry Working Group of the German, C.F. Registry. Use of elexacaftor/tezacaftor/ivacaftor leads to changes in detection frequencies of Staphylococcus aureus and Pseudomonas aeruginosa dependent on age and lung function in people with cystic fibrosis. Int. J. Infect. Dis. 2024, 139, 124–131. [Google Scholar] [CrossRef]
- Pollak, M.; Gambazza, S.; Orenti, A.; De Rose, V.; Prais, D.; Kerem, E.; Zahav, M.M. ECFSPR Steering Group. Respiratory infections after elexacaftor/tezacaftor/ivacaftor treatment in people with cystic fibrosis: Analysis of the European Cystic Fibrosis Society Patient Registry. ERJ Open Res. 2025, in press. [Google Scholar] [CrossRef]
- Muhlebach, M.S.; She, J.; Zhang, E.Y.; Cogen, J.D.; Kosorok, M.R. Changes in factors associated with inhaled antibiotic prescriptions for people with cystic fibrosis over time in the U.S. J. Cyst. Fibros. 2025, 24, 98–104. [Google Scholar] [CrossRef]
- Calthorpe, R.; Rosenfeld, M.; Goss, C.H.; Green, N.; Derleth, M.; Carr, S.B.; Smyth, A.; Stewart, I. Pancreatic enzyme prescription following ivacaftor licensing: A retrospective analysis of the US and UK cystic fibrosis registries. J. Cyst. Fibros. 2024, 23, 746–753. [Google Scholar] [CrossRef]
- Caley, L.R.; Jarosz-Griffiths, H.H.; Smith, L.; Gale, L.; Barrett, J.; Kinsey, L.; Davey, V.; Nash, M.; Jones, A.M.; Whitehouse, J.L.; et al. Body mass index and nutritional intake following Elexacaftor/Tezacaftor/Ivacaftor modulator therapy in adults with cystic fibrosis. J. Cyst. Fibros. 2023, 22, 1002–1009. [Google Scholar] [CrossRef] [PubMed]
- Szentpetery, S.; Fernandez, G.S.; Schechter, M.S.; Jain, R.; Flume, P.A.; Fink, A.K. Obesity in Cystic fibrosis: Prevalence, trends and associated factors data from the US cystic fibrosis foundation patient registry. J. Cyst. Fibros. 2022, 21, 777–783. [Google Scholar] [CrossRef] [PubMed]
- Patil, R.; Magaret, A.S.; Jain, R.; Taylor-Cousar, J.; Hughan, K.S.; Kazmerski, T.M. Factors associated with pubertal growth outcomes in cystic fibrosis: Early Growth and Puberty in CF. J. Cyst. Fibros. 2024, 23, 538–544. [Google Scholar] [CrossRef]
- Nielsen, B.U.; Olsen, M.F.; Mabuza Mathiesen, I.H.; Pressler, T.; Ritz, C.; Katzenstein, T.L.; Olesen, H.V.; Skov, M.; Jensen-Fangel, S.; Almdal, T.P.; et al. Decline in HbA1c during the first year of elexacaftor/tezacaftor/ivacaftor treatment in the Danish cystic fibrosis cohort: Short title: Decline in HbA1c after elexacaftor/tezacaftor/ivacaftor treatment. J. Cyst. Fibros. 2024, 23, 103–108. [Google Scholar] [CrossRef] [PubMed]
- Gifford, A.H.; Heltshe, S.L.; Goss, C.H. CFTRm Use Is Associated with Higher Hemoglobin Levels in Individuals with Cystic Fibrosis. Ann. Am. Thorac. Soc. 2019, 16, 331–340. [Google Scholar] [CrossRef] [PubMed]
- Kirwan, L.; Fletcher, G.; Harrington, M.; Jeleniewska, P.; Zhou, S.; Casserly, B.; Gallagher, C.G.; Greally, P.; Gunaratnam, C.; Herzig, M.; et al. Longitudinal Trends in Real-World Outcomes after Initiation of Ivacaftor. A Cohort Study from the Cystic Fibrosis Registry of Ireland. Ann. Am. Thorac. Soc. 2019, 16, 209–216. [Google Scholar] [CrossRef]
- Granger, E.; Davies, G.; Keogh, R.H. Treatment patterns in people with cystic fibrosis: Have they changed since the introduction of ivacaftor? J. Cyst. Fibros. 2022, 21, 316–322. [Google Scholar] [CrossRef]
- Keogh, R.H.; Cosgriff, R.; Andrinopoulou, E.R.; Brownlee, K.G.; Carr, S.B.; Diaz-Ordaz, K.; Granger, E.; Jewell, N.P.; Lewin, A.; Leyrat, C.; et al. Projecting the impact of triple CFTRm therapy on intravenous antibiotic requirements in cystic fibrosis using patient registry data combined with treatment effects from randomised trials. Thorax 2022, 77, 873–881. [Google Scholar] [CrossRef]
- Råket, H.K.; Ankarfeldt, M.Z.; Wang, J.N.; Pressler, T.; Jensen-Fangel, S.; Qvist, T.; Faurholt-Jepsen, D.; Jimenez-Solem, E.; Petersen, J.; Jensen, C.B.; et al. Elexacaftor/Tezacaftor/Ivacaftor for Cystic Fibrosis: Impact on Hospitalizations and Health Care Resource Utilization in a Universal Health Care Setting. Pulm. Ther. 2025, 11, 235–247. [Google Scholar] [CrossRef]
- Råket, H.K.; Jensen, C.B.; Wang, J.N.; Pressler, T.; Olesen, H.V.; Skov, M.; Jensen-Fangel, S.; Petersen, J.; Jimenez-Solem, E.; TransformCF study group. Impact of elexacaftor/tezacaftor/ivacaftor on utilization of routine therapies in cystic fibrosis: Danish nationwide register study. J. Cyst. Fibros. 2025, 24, 105–111. [Google Scholar] [CrossRef]
- Heltshe, S.L.; Godfrey, E.M.; Josephy, T.; Aitken, M.L.; Taylor-Cousar, J.L. Pregnancy among cystic fibrosis women in the era of CFTRms. J. Cyst. Fibros. 2017, 16, 687–694. [Google Scholar] [CrossRef] [PubMed]
- Martin, C.; Burnet, E.; Ronayette-Preira, A.; de Carli, P.; Martin, J.; Delmas, L.; Prieur, B.; Burgel, P.R. Patient perspectives following initiation of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis and advanced lung disease. Respir. Med. Res. 2021, 80, 100829. [Google Scholar] [CrossRef] [PubMed]
- Ramsey, B.; Correll, C.U.; DeMaso, D.R.; McKone, E.; Tullis, E.; Taylor-Cousar, J.L.; Chu, C.; Volkova, N.; Ahluwalia, N.; Waltz, D.; et al. Elexacaftor/Tezacaftor/Ivacaftor Treatment and Depression-related Events. Am. J. Respir. Crit. Care Med. 2024, 209, 299–306. [Google Scholar] [CrossRef]
- McGarry, L.J.; Bhaiwala, Z.; Lopez, A.; Chandler, C.; Pelligra, C.G.; Rubin, J.L.; Liou, T.G. Calibration and validation of modeled 5-year survival predictions among people with cystic fibrosis treated with the cystic fibrosis transmembrane conductance regulator modulator ivacaftor using United States registry data. PLoS ONE 2023, 18, e0283479. [Google Scholar] [CrossRef]
- Sawicki, G.S.; Fink, A.K.; Schechter, M.S.; Loeffler, D.R.; Mayer-Hamblett, N. Rate and predictors of prescription of lumacaftor—Ivacaftor in the 18 months following approval in the United States. J. Cyst. Fibros. 2018, 17, 742–746. [Google Scholar] [CrossRef]
- Rubin, J.L.; O’Callaghan, L.; Pelligra, C.; Konstan, M.W.; Ward, A.; Ishak, J.K.; Chandler, C.; Liou, T.G. Modeling long-term health outcomes of patients with cystic fibrosis homozygous for F508del-CFTR treated with lumacaftor/ivacaftor. Ther. Adv. Respir. Dis. 2019, 13, 1753466618820186. [Google Scholar] [CrossRef]
- Kondratyeva, E.I.; Fatkhullina, I.R.; Zhekaite, E.K.; Sherman, V.D.; Voronkova, A.Y. Efficacy and safety of the CFTR-modulator lumacaftor/ivacaftor use in patients with cystic fibrosis in different age groups. Pediatr. J. Named After G.N. Speransky 2024, 103, 46–56. [Google Scholar] [CrossRef]
- Lindblad, A.; Monestrol, I.; Gilljam, M.; Krantz, C.; McGarry, L.J.; Banefelt, J.; Aldvén, M. Clinical, economic, and societal burden of cystic fibrosis and the impact of the CFTRm, lumacaftor/ivacaftor: An assessment using linked registry data in Sweden. J. Med. Econ. 2024, 27, 897–906. [Google Scholar] [CrossRef] [PubMed]
- Stanojevic, S.; Vukovojac, K.; Sykes, J.; Ratjen, F.; Tullis, E.; Stephenson, A.L. Projecting the impact of delayed access to elexacaftor/tezacaftor/ivacaftor for people with Cystic Fibrosis. J. Cyst. Fibros. 2021, 20, 243–249. [Google Scholar] [CrossRef]
- Lopez, A.; Daly, C.; Vega-Hernandez, G.; MacGregor, G.; Rubin, J.L. Elexacaftor/tezacaftor/ivacaftor projected survival and long-term health outcomes in people with cystic fibrosis homozygous for F508del. J. Cyst. Fibros. 2023, 22, 607–614. [Google Scholar] [CrossRef]
- Vega-Hernandez, G.; Duran, A.; Akbari, A.; Griffiths, R.; Wöhling, A. CFTR-Modulators (CFTRM) Impact on Real-World Healthcare Resource Utilisation (HCRU) in Cystic Fibrosis (CF) in Wales: Retrospective, Observational, Database Study Using Linked Data from the UK CF Registry (UKCFR) and Sail-Databank. Value Health 2023, 26, S92. [Google Scholar] [CrossRef]
- Hergenroeder, G.E.; Todd, J.V.; Ostrenga, J.S.; Goss, C.H.; Jain, R.; Morgan, W.; Sawicki, G.S.; Schechter, M.S.; Cromwell, E.A.; Ren, C.L. Factors associated with prescription of elexacaftor/tezacaftor/ivacaftor among people with cystic fibrosis aged 12 years or older with at least one F508del allele. J. Cyst. Fibros. 2025, 24, 135–141. [Google Scholar] [CrossRef]
- Çobanoğlu, N.; Özçelik, U.; Çakır, E.; Şişmanlar Eyüboğlu, T.; Pekcan, S.; Cinel, G.; Yalçın, E.; Kiper, N.; Emiralioğlu, N.; Şen, V.; et al. Patients eligible for modulator drugs: Data from cystic fibrosis registry of Turkey. Pediatr. Pulmonol. 2020, 55, 2302–2306. [Google Scholar] [CrossRef]
- Sanders, D.B.; Mayer-Hamblett, N.; Rosenfeld, M.; Polinieni, D.; Dasenbrook, E.; Szczesniak, R.; Cromwell, E.A. Characteristics of individuals with cystic fibrosis in the United States ineligible for ivacaftor and elexacaftor/tezacaftor/ivacaftor. J. Cyst. Fibros. 2025, 24, 255–262. [Google Scholar] [CrossRef]
- Guo, J.; Garratt, A.; Hill, A. Worldwide rates of diagnosis and effective treatment for cystic fibrosis. J. Cyst. Fibros. 2022, 21, 456–462. [Google Scholar] [CrossRef] [PubMed]
- Tomlinson, O.W.; Mitchelmore, P.; Williams, C.A. Comparison of Reporting Quality in National Cystic Fibrosis Patient Registries: Implications for Identifying Use of Novel CFTRms. Pulm. Ther. 2024, 10, 427–438. [Google Scholar] [CrossRef]
- Kerem, E.; Orenti, A.; Adamoli, A.; Hatziagorou, E.; Naehrlich, L.; Sermet-Gaudelus, I.; The ECFS Patient Registry Steering Group. Cystic fibrosis in Europe: Improved lung function and longevity—Reasons for cautious optimism, but challenges remain. Eur. Respir. J. 2024, 63, 2301241. [Google Scholar] [CrossRef] [PubMed]
- Kondratyeva, E.; Melyanovskaya, Y.; Sherman, V.; Voronkova, A.; Zhekaite, E.; Krasovsky, S.; Amelina, E.; Kashirskaya, N.; Shadrina, V.; Polyakov, A.; et al. Study of the genetic and molecular epidemiology of cystic fibrosis based on the patient registry for planning targeted therapy in Russian Federation. Front. Genet. 2024, 15, 1383033. [Google Scholar] [CrossRef]
- Akgül Erdal, M.; Nayır Büyükşahin, H.; Şen, V.; Ayzıt Kılınç, A.; Çokuğraş, H.; Doğan, G.; Yılmaz, A.İ.; Ünal, G.; Serbes, M.; Altıntaş, D.U.; et al. Eligibility of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator therapies: Cohort of cystic fibrosis registry of Türkiye. Turk. J. Pediatr. 2025, 67, 22–30. [Google Scholar] [CrossRef]
- Sawicki, G.S.; McKone, E.F.; Pasta, D.J.; Millar, S.J.; Wagener, J.S.; Johnson, C.A.; Konstan, M.W. Sustained Benefit from ivacaftor demonstrated by combining clinical trial and cystic fibrosis patient registry data. Am. J. Respir. Crit. Care Med. 2015, 192, 836–842. [Google Scholar] [CrossRef]
- Bessonova, L.; Volkova, N.; Higgins, M.; Bengtsson, L.; Tian, S.; Simard, C.; Konstan, M.W.; Sawicki, G.S.; Sewall, A.; Nyangoma, S.; et al. Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor. Thorax 2018, 73, 731–740. [Google Scholar] [CrossRef] [PubMed]
- Volkova, N.; Moy, K.; Evans, J.; Campbell, D.; Tian, S.; Simard, C.; Higgins, M.; Konstan, M.W.; Sawicki, G.S.; Elbert, A.; et al. Disease progression in patients with cystic fibrosis treated with ivacaftor: Data from national US and UK registries. J. Cyst. Fibros. 2020, 19, 68–79. [Google Scholar] [CrossRef] [PubMed]
- Higgins, M.; Volkova, N.; Moy, K.; Marshall, B.C.; Bilton, D. Real-World Outcomes Among Patients with Cystic Fibrosis Treated with Ivacaftor: 2012–2016 Experience. Pulm. Ther. 2020, 6, 141–149. [Google Scholar] [CrossRef] [PubMed]
- Kawala, C.R.; Ma, X.; Sykes, J.; Stanojevic, S.; Coriati, A.; Stephenson, A.L. Real-world use of ivacaftor in Canada: A retrospective analysis using the Canadian Cystic Fibrosis Registry. J. Cyst. Fibros. 2021, 20, 1040–1045. [Google Scholar] [CrossRef] [PubMed]
- Salvatore, D.; Carnovale, V.; Majo, F.; Padoan, R.; Salvatore, M.; Taruscio, D.; Amato, A.; Ferrari, G.; Campagna, G. Cystic fibrosis with non-G551D gating mutations in Italy: Epidemiology and clinical characteristics. Pediatr. Pulmonol. 2021, 56, 442–449. [Google Scholar] [CrossRef]
- Kim, C.; Higgins, M.; Liu, L.; Volkova, N.; Zolin, A.; Naehrlich, L.; Group, E.S. Effectiveness of lumacaftor/ivacaftor initiation in children with cystic fibrosis aged 2 through 5 years on disease progression: Interim results from an ongoing registry-based study. J. Cyst. Fibros. 2024, 23, 436–442. [Google Scholar] [CrossRef]
- Burgel, P.R.; Munck, A.; Durieu, I.; Chiron, R.; Mely, L.; Prevotat, A.; Murris-Espin, M.; Porzio, M.; Abely, M.; Reix, P.; et al. Real-Life Safety and Effectiveness of Lumacaftor-Ivacaftor in Patients with Cystic Fibrosis. Am. J. Respir. Crit. Care Med. 2020, 201, 188–197. [Google Scholar] [CrossRef]
- Burgel, P.R.; Durieu, I.; Chiron, R.; Ramel, S.; Danner-Boucher, I.; Prevotat, A.; Grenet, D.; Marguet, C.; Reynaud-Gaubert, M.; Macey, J.; et al. Rapid Improvement after Starting Elexacaftor-Tezacaftor-Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease. Am. J. Respir. Crit. Care Med. 2021, 204, 64–73. [Google Scholar] [CrossRef]
- Bower, J.K.; Volkova, N.; Ahluwalia, N.; Sahota, G.; Xuan, F.; Chin, A.; Weinstock, T.G.; Ostrenga, J.; Elbert, A. Real-world safety and effectiveness of elexacaftor/tezacaftor/ivacaftor in people with cystic fibrosis: Interim results of a long-term registry-based study. J. Cyst. Fibros. 2023, 22, 730–737. [Google Scholar] [CrossRef]
- Kondratyeva, E.I.; Odinaeva, N.D.; Zhekaite, E.K.; Pasnova, E.V.; Fatkhullina, I.R.; Maksimycheva, T.Y.; Sherman, V.D.; Kutsev, S.I. Efficacy of CFTRms in clinical practice (6-month follow-up). Pulmonologiya 2023, 33, 189–197. [Google Scholar] [CrossRef]
- Muhlebach, M.S.; Clancy, J.P.; Heltshe, S.L.; Ziady, A.; Kelley, T.; Accurso, F.; Pilewski, J.; Mayer-Hamblett, N.; Joseloff, E.; Sagel, S.D. Biomarkers for cystic fibrosis drug development. J. Cyst. Fibros. 2016, 15, 714–723. [Google Scholar] [CrossRef] [PubMed]
- Bene, Z.; Fejes, Z.; Macek, M., Jr.; Amaral, M.D.; Balogh, I.; Nagy, B., Jr. Laboratory biomarkers for lung disease severity and progression in cystic fibrosis. Clin. Chim. Acta 2020, 508, 277–286. [Google Scholar] [CrossRef] [PubMed]
- McNally, P.; Linnane, B.; Williamson, M.; Elnazir, B.; Short, C.; Saunders, C.; Kirwan, L.; Rea, D.; Van de Corput, M.P.C.K.; Tiddens, H.A.W.M.; et al. The clinical impact of lumacaftor-ivacaftor on structural lung disease and lung function in children aged 6–11 with cystic fibrosis in a real-world setting. Respir. Res. 2023, 24, 199. [Google Scholar] [CrossRef] [PubMed]
- Tong, K.; Barker, D.; France, M.; Burr, L.; Greville, H.; Visser, S.; Middleton, P.; Wainwright, C.; Dorahy, D.; Wark, P. Lumacaftor/ivacaftor reduces exacerbations in adults homozygous for Phe508del mutation with severe lung disease. J. Cyst. Fibros. 2020, 19, 415–420. [Google Scholar] [CrossRef]
- Sagel, S.D.; Khan, U.; Heltshe, S.L.; Clancy, J.P.; Borowitz, D.; Gelfond, D.; Donaldson, S.H.; Moran, A.; Ratjen, F.; VanDalfsen, J.M.; et al. Clinical Effectiveness of Lumacaftor/Ivacaftor in Patients with Cystic Fibrosis Homozygous for F508del-CFTR. A Clinical Trial. Ann. Am. Thorac. Soc. 2021, 18, 75–83. [Google Scholar] [CrossRef]
- Griese, M.; Costa, S.; Linnemann, R.W.; Mall, M.A.; McKone, E.F.; Polineni, D.; Quon, B.S.; Ringshausen, F.C.; Taylor-Cousar, J.L.; Withers, N.J.; et al. Safety and efficacy of elexacaftor/tezacaftor/ivacaftor for 24 weeks or longer in people with cystic fibrosis and one or more F508del alleles: Interim results of an open-label phase 3 clinical trial. Am. J. Respir. Crit. Care Med. 2020, 203, 381–385. [Google Scholar] [CrossRef]
- Daines, C.L.; Polineni, D.; Tullis, E.; Costa, S.; Linnemann, R.W.; Mall, M.A.; McKone, E.F.; Quon, B.S.; Ringshausen, F.C.; Selvadurai, H.; et al. Long-Term Safety and Efficacy of Elexacaftor/Tezacaftor/Ivacaftor in Adults and Adolescents with Cystic Fibrosis and at Least One F508del Allele: A Phase 3, Open-Label Extension Study. Am. J. Respir. Crit. Care Med. 2025, in press. [CrossRef]
- Dasenbrook, E.C.; Sawicki, G.S. Cystic fibrosis patient registries: A valuable source for clinical research. J. Cyst. Fibros. 2018, 17, 433–440. [Google Scholar] [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Salvatore, D.; Pepe, A. Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence. J. Clin. Med. 2025, 14, 3978. https://doi.org/10.3390/jcm14113978
Salvatore D, Pepe A. Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence. Journal of Clinical Medicine. 2025; 14(11):3978. https://doi.org/10.3390/jcm14113978
Chicago/Turabian StyleSalvatore, Donatello, and Angela Pepe. 2025. "Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence" Journal of Clinical Medicine 14, no. 11: 3978. https://doi.org/10.3390/jcm14113978
APA StyleSalvatore, D., & Pepe, A. (2025). Cystic Fibrosis Transmembrane Conductance Regulator Modulators in Cystic Fibrosis: A Review of Registry-Based Evidence. Journal of Clinical Medicine, 14(11), 3978. https://doi.org/10.3390/jcm14113978