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Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor

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 p...

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Autores principales: Bessonova, Leona, Volkova, Nataliya, Higgins, Mark, Bengtsson, Leif, Tian, Simon, Simard, Christopher, Konstan, Michael W, Sawicki, Gregory S, Sewall, Ase, Nyangoma, Stephen, Elbert, Alexander, Marshall, Bruce C, Bilton, Diana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204955/
https://www.ncbi.nlm.nih.gov/pubmed/29748252
http://dx.doi.org/10.1136/thoraxjnl-2017-210394
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author Bessonova, Leona
Volkova, Nataliya
Higgins, Mark
Bengtsson, Leif
Tian, Simon
Simard, Christopher
Konstan, Michael W
Sawicki, Gregory S
Sewall, Ase
Nyangoma, Stephen
Elbert, Alexander
Marshall, Bruce C
Bilton, Diana
author_facet Bessonova, Leona
Volkova, Nataliya
Higgins, Mark
Bengtsson, Leif
Tian, Simon
Simard, Christopher
Konstan, Michael W
Sawicki, Gregory S
Sewall, Ase
Nyangoma, Stephen
Elbert, Alexander
Marshall, Bruce C
Bilton, Diana
author_sort Bessonova, Leona
collection PubMed
description 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
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spelling pubmed-62049552018-11-08 Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor Bessonova, Leona Volkova, Nataliya Higgins, Mark Bengtsson, Leif Tian, Simon Simard, Christopher Konstan, Michael W Sawicki, Gregory S Sewall, Ase Nyangoma, Stephen Elbert, Alexander Marshall, Bruce C Bilton, Diana Thorax Cystic Fibrosis 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 BMJ Publishing Group 2018-08 2018-05-10 /pmc/articles/PMC6204955/ /pubmed/29748252 http://dx.doi.org/10.1136/thoraxjnl-2017-210394 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. 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/
spellingShingle Cystic Fibrosis
Bessonova, Leona
Volkova, Nataliya
Higgins, Mark
Bengtsson, Leif
Tian, Simon
Simard, Christopher
Konstan, Michael W
Sawicki, Gregory S
Sewall, Ase
Nyangoma, Stephen
Elbert, Alexander
Marshall, Bruce C
Bilton, Diana
Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
title Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
title_full Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
title_fullStr Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
title_full_unstemmed Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
title_short Data from the US and UK cystic fibrosis registries support disease modification by CFTR modulation with ivacaftor
title_sort data from the us and uk cystic fibrosis registries support disease modification by cftr modulation with ivacaftor
topic Cystic Fibrosis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204955/
https://www.ncbi.nlm.nih.gov/pubmed/29748252
http://dx.doi.org/10.1136/thoraxjnl-2017-210394
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