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Cystic fibrosis
Original article
Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
  1. Leona Bessonova1,
  2. Nataliya Volkova1,
  3. Mark Higgins2,
  4. Leif Bengtsson1,
  5. Simon Tian1,
  6. Christopher Simard1,
  7. Michael W Konstan3,
  8. Gregory S Sawicki4,
  9. Ase Sewall5,
  10. Stephen Nyangoma6,
  11. Alexander Elbert7,
  12. Bruce C Marshall7,
  13. Diana Bilton6,8
  1. 1 Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA
  2. 2 Vertex Pharmaceuticals (Europe) Limited, London, UK
  3. 3 Case Western Reserve University School of Medicine and Rainbow Babies and Children’s Hospital, Cleveland, Ohio, USA
  4. 4 Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
  5. 5 Sewall Inc, Bethesda, Maryland, USA
  6. 6 Imperial College London, London, UK
  7. 7 US CF Foundation, Maryland, UK
  8. 8 UK CF Registry, London, UK
  1. Correspondence to Dr Nataliya Volkova, Vertex Pharmaceuticals Incorporated, Boston MA 02210, USA; Nataliya_Volkova{at}vrtx.com

Abstract

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

  • cystic fibrosis
  • systemic disease and lungs
  • respiratory infection
  • rare lung diseases

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/thoraxjnl-2017-210394

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    Footnotes

    • Contributors LBes, NV, MH, LBen, ST and CS conceived the study. LBes, NV, MH, LBen, ST, CS, BCM and DB designed the study. AS, SN and AE acquired the data. LBes, NV, LBen, ST, CS, AS, SN and AE analysed the data. All authors interpreted the data. LBes and NV drafted the manuscript. All authors critically revised the manuscript for important intellectual content and approved the manuscript for publication.

    • Funding This study was sponsored by Vertex Pharmaceuticals Incorporated.

    • Competing interests MH, CS, ST and NV are employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in that company. LB and LB are former employees of Vertex Pharmaceuticals Incorporated and may own stock or stock options in that company. GSS has served on advisory boards for Vertex Pharmaceuticals Incorporated and on the US CFFPR committee. AE is an employee and AS is a contractor for the US CF Foundation, which provided data for this study. BCM is an employee of the CF Foundation. DB and SN are members of the Steering Committee of the UK CF Registry, which provided data for this study. MWK is a consultant to Vertex Pharmaceuticals Incorporated.

    • Patient consent Not required.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Author note Leona Bessonova and Leif Bengtsson were employees of Vertex Pharmaceuticals Incorporated at the time of this study.