Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
Open accessAbstract
Background: Ivacaftor is the first cystic fibrosis transmembrane conductance regulator (CFTR) modulator demonstrating clinical benefit in patients with cystic fibrosis (CF). As ivacaftor is intended for chronic, lifelong use, understanding long-term effects is important for patients and healthcare providers. Objective: This ongoing, observational, postapproval safety study evaluates clinical outcomes and disease progression in ivacaftor-treated patients using data from the US and the UK CF registries following commercial availability. Methods: Annual analyses compare ivacaftor-treated and untreated matched comparator patients for: risks of death, transplantation, hospitalisation, pulmonary exacerbation; prevalence of CF-related complications and microorganisms and lung function changes in a subset of patients who initiated ivacaftor in the first year of commercial availability. Results from the 2014 analyses (2 and 3 years following commercial availability in the UK and USA, respectively) are presented here. Results: Analyses included 1256 ivacaftor-treated and 6200 comparator patients from the USA and 411 ivacaftor-treated and 2069 comparator patients from the UK. No new safety concerns were identified based on the evaluation of clinical outcomes included in the analyses. As part of safety evaluations, ivacaftor-treated US patients were observed to have significantly lower risks of death (0.6% vs 1.6%, p=0.0110), transplantation (0.2% vs 1.1%, p=0.0017), hospitalisation (27.5% vs 43.1%, p<0.0001) and pulmonary exacerbation (27.8% vs 43.3%, p<0.0001) relative to comparators; trends were similar in the UK. In both registries, ivacaftor-treated patients had a lower prevalence of CF-related complications and select microorganisms and had better preserved lung function. Conclusions: While general limitations of observational research apply, analyses revealed favourable results for clinically important outcomes among ivacaftor-treated patients, adding to the growing body of literature supporting disease modification by CFTR modulation with ivacaftor. EU PAS registration number: EUPAS4270
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The current benchmark for highly effective CFTR modulator therapy is ivacaftor for patients with the Gly551Asp CFTR mutation, in whom disease modification has been shown with long-term use, including decreased lung-function decline and decreased mortality.
“The current benchmark for highly effective CFTR modulator therapy is ivacaftor for patients with the Gly551Asp CFTR mutation,10 in whom disease modification has been shown with long-term use, including decreased lung-function decline and decreased mortality.25-28”
From Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele (2019) · cites this paper as [28]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIVA therapy has been shown to be associated with a decreased need for lung transplant and improved survival with long-term use.
“IVA therapy has also been shown to be associated with a decreased need for lung transplant and improved survival with long-term use.22,23”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
No references could be resolved yet.
Research works printed but not linked: 20
- [2]Knapp EA, Fink AK, Goss CH, et al The Cystic Fibrosis Foundation Patient Registry. Design and Methods of a National Observational Disease Registry. Ann Am Thorac Soc 2016; 13: 1173– 9. 10.1513/AnnalsATS.201511-781OC 27078236 · DOI
- [4]Ramsey BW, Davies J, McElvaney NG, et al A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med 2011; 365: 1663– 72. 10.1056/NEJMoa1105185 22047557 PMC3230303 · DOI · Paper page
- [5]Davies JC, Wainwright CE, Canny GJ, et al Efficacy and safety of ivacaftor in patients aged 6 to 11 years with cystic fibrosis with a G551D mutation. Am J Respir Crit Care Med 2013; 187: 1219– 25. 10.1164/rccm.201301-0153OC 23590265 PMC3734608 · DOI
- [6]De Boeck K, Munck A, Walker S, et al Efficacy and safety of ivacaftor in patients with cystic fibrosis and a non-G551D gating mutation. J Cyst Fibros 2014; 13: 674– 80. 10.1016/j.jcf.2014.09.005 25266159 · DOI
- [7]Moss RB, Flume PA, Elborn JS, 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; 3: 524– 33. 10.1016/S2213-2600(15)00201-5 26070913 PMC4641035 · DOI
- [8]Taylor-Robinson D, Archangelidi O, Carr SB, et al Data Resource Profile: The UK Cystic Fibrosis Registry. Int J Epidemiol 2018; 47: 9– 10. 10.1093/ije/dyx196 29040601 PMC5837577 · DOI
- [9]McKone EF, Emerson SS, Edwards KL, et al Effect of genotype on phenotype and mortality in cystic fibrosis: a retrospective cohort study. Lancet 2003; 361: 1671– 6. 10.1016/S0140-6736(03)13368-5 12767731 · DOI
- [10]Sawicki GS, McKone EF, Millar SJ, et al Patients with Cystic Fibrosis and a G551D or Homozygous F508del Mutation: Similar Lung Function Decline. Am J Respir Crit Care Med 2017; 195: 1673– 6. 10.1164/rccm.201608-1678LE 28617084 · DOI
- [11]McKone EF, Borowitz D, Drevinek P, et al Long-term safety and efficacy of ivacaftor in patients with cystic fibrosis who have the Gly551Asp-CFTR mutation: a phase 3, open-label extension study (PERSIST). Lancet Respir Med 2014; 2: 902– 10. 10.1016/S2213-2600(14)70218-8 25311995 · DOI · Paper page
- [12]Sawicki GS, McKone EF, Pasta DJ, et al Sustained Benefit from ivacaftor demonstrated by combining clinical trial and cystic fibrosis patient registry data. Am J Respir Crit Care Med 2015; 192: 836– 42. 10.1164/rccm.201503-0578OC 26132840 · DOI · Paper page
- [13]Sanders DB, Bittner RC, Rosenfeld M, et al Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med 2010; 182: 627– 32. 10.1164/rccm.200909-1421OC 20463179 PMC5450763 · DOI
- [14]Liou TG, Adler FR, Fitzsimmons SC, et al Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol 2001; 153: 345– 52. 10.1093/aje/153.4.345 11207152 PMC2198936 · DOI · Paper page
- [15]Heltshe SL, Mayer-Hamblett N, Burns JL, et al Pseudomonas aeruginosa in cystic fibrosis patients with G551D-CFTR treated with ivacaftor. Clin Infect Dis 2015; 60: 703– 12. 10.1093/cid/ciu944 25425629 PMC4342673 · DOI
- [16]Ronan NJ, O’Callaghan G, Harrison MJ, et al 37 Clinical outcomes of real world Kalydeco (CORK) study. Journal of Cystic Fibrosis 2014; 13: S56 10.1016/S1569-1993(14)60174-0 · DOI
- [17]Sheikh SI, Long FR, McCoy KS, et al Computed tomography correlates with improvement with ivacaftor in cystic fibrosis patients with G551D mutation. J Cyst Fibros 2015; 14: 84– 9. 10.1016/j.jcf.2014.06.011 25049054 · DOI
- [18]Guhaniyogi L, Speight L, Lea-Davies M, et al 135 Transformational care at the All Wales Adult CF Centre (AWACFC) – the impact of ivacaftor (Kalydeco®) one year on. Journal of Cystic Fibrosis 2015; 14(suppl 1): S92 10.1016/S1569-1993(15)30312-X · DOI
- [19]Rowe SM, Heltshe SL, Gonska T, et al Clinical mechanism of the cystic fibrosis transmembrane conductance regulator potentiator ivacaftor in G551D-mediated cystic fibrosis. Am J Respir Crit Care Med 2014; 190: 175– 84. 10.1164/rccm.201404-0703OC 24927234 PMC4226057 · DOI · Paper page
- [22]Schwarzenberg SJ, Thomas W, Olsen TW, et al Microvascular complications in cystic fibrosis-related diabetes. Diabetes Care 2007; 30: 1056– 61. 10.2337/dc06-1576 17322485 · DOI
- [23]Bellin MD, Laguna T, Leschyshyn J, et al Insulin secretion improves in cystic fibrosis following ivacaftor correction of CFTR: a small pilot study. Pediatr Diabetes 2013; 14: 417– 21. 10.1111/pedi.12026 23952705 PMC3804832 · DOI
- [24]Banerjee A, Brennan A, Horsley A, et al P195 Prospective Examination Of The Effects Of Ivacaftor On Glycaemic Health. Thorax 2014; 69(Suppl 2): A162 10.1136/thoraxjnl-2014-206260.324 · DOI
Cited by
Sorted by citations
Elexacaftor–Tezacaftor–Ivacaftor for Cystic Fibrosis with a Single Phe508del Allele
Middleton, P. G., Mall, M. A., Dřevínek, P., Lands, L. C., McKone, E. F., Polineni, D., Ramsey, B. W., Taylor-Cousar, J. L., Tullis, E., Vermeulen, F., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1908639 · Cited by 2,198 · see citing works
Self-citationHeijerman, H. G. M., McKone, E. F., Downey, D. G., Van Braeckel, E., Rowe, S. M., Tullis, E., Mall, M. A., Welter, J. J., Ramsey, B. W., McKee, C. M., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)32597-8 · Cited by 1,414 · see citing works
Self-citationCFTR modulator therapy: Transforming the landscape of clinical care in cystic fibrosis
Taylor-Cousar, J. L., Robinson, P. D., Shteinberg, M., & Downey, D. G. (2023) · The Lancet · doi:10.1016/s0140-6736(23)01609-4 · Cited by 173 · see citing works
Bower, J. K., Volkova, N., Ahluwalia, N., Sahota, G., Xuan, F., Chin, A., Weinstock, T. G., Ostrenga, J., & Elbert, A. (2023) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2023.03.002 · Cited by 140 · see citing works
Self-citationGranger, E., Davies, G., & Keogh, R. H. (2022) · Journal of Cystic Fibrosis · doi:10.1016/j.jcf.2021.08.014 · Cited by 21 · see citing works
- Authors
- Bessonova, L., Volkova, N., Higgins, M., Bengtsson, L., Tian, S., Simard, C., Konstan, M. W., Sawicki, G. S., Sewall, A., Nyangoma, S., Elbert, A., Marshall, B. C., & Bilton, D.
- Affiliations
- Vertex Pharmaceuticals (United States) (US)
- Vertex Pharmaceuticals (United Kingdom) (GB)
- Rainbow Babies & Children's Hospital (US)
- Boston Children's Hospital (US)
- Imperial College London (GB)
- Corresponding author
- Volkova, Nataliya
- ORCID
- Venue
- Thorax
- Publisher
- BMJ
- Published
- 2018-05-10
- Volume
- 73
- Issue
- 8
- Pages
- 731-740
- ISSN
- 0040-6376 (ISSN-L)
- 1468-3296
- PMC
- PMC6204955
- OpenAlex
- W2799520701
- Cited by
- 214
- References
- 0
- Citations by year
- 2026: 10 · 2025: 25 · 2024: 17 · 2023: 28 · 2022: 45 · 2021: 36 · 2020: 23 · 2019: 27 · 2018: 3
- FWCI
- 16.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Thorax (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Funders
- Vertex Pharmaceuticals Incorporated
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cystic Fibrosis Research Advances
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
- Keywords
- ivacaftor, cystic fibrosis, CFTR modulators, disease modification, long-term safety, mortality, lung transplantation, hospitalization, pulmonary exacerbations, lung function
- MeSH terms
- Adolescent, Adult, Aminophenols, Child, Child, Preschool, Cystic Fibrosis, Female, United Kingdom, Humans, Infant, Male, Registries, Respiratory Function Tests, United States, Quinolones, Treatment Outcome, Disease Progression, Chloride Channel Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
