Cargando…

Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis

BACKGROUND: Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD. METHODS: This post-hoc analys...

Descripción completa

Detalles Bibliográficos
Autores principales: Bafadhel, Mona, Singh, Dave, Jenkins, Christine, Peterson, Stefan, Bengtsson, Thomas, Wessman, Peter, Fagerås, Malin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954504/
https://www.ncbi.nlm.nih.gov/pubmed/31924197
http://dx.doi.org/10.1186/s12931-020-1280-y
_version_ 1783486806590750720
author Bafadhel, Mona
Singh, Dave
Jenkins, Christine
Peterson, Stefan
Bengtsson, Thomas
Wessman, Peter
Fagerås, Malin
author_facet Bafadhel, Mona
Singh, Dave
Jenkins, Christine
Peterson, Stefan
Bengtsson, Thomas
Wessman, Peter
Fagerås, Malin
author_sort Bafadhel, Mona
collection PubMed
description BACKGROUND: Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD. METHODS: This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation. Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV(1)] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models. RESULTS: The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69–84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM. All components contributed to the CID event rate. Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events. The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count. CONCLUSIONS: Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels. CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development.
format Online
Article
Text
id pubmed-6954504
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-69545042020-01-14 Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis Bafadhel, Mona Singh, Dave Jenkins, Christine Peterson, Stefan Bengtsson, Thomas Wessman, Peter Fagerås, Malin Respir Res Research BACKGROUND: Clinically Important Deterioration (CID) is a novel composite measure to assess treatment effect in chronic obstructive pulmonary disease (COPD). We examined the performance and utility of CID in assessing the effect of inhaled corticosteroids (ICS) in COPD. METHODS: This post-hoc analysis of four budesonide/formoterol (BUD/FORM) studies comprised 3576 symptomatic moderate-to-very-severe COPD patients with a history of exacerbation. Analysis of time to first CID event (exacerbation, deterioration in forced expiratory volume in 1 second [FEV(1)] or worsening St George’s Respiratory Questionnaire [SGRQ] score) was completed using Cox proportional hazards models. RESULTS: The proportion of patients with ≥1 CID in the four studies ranged between 63 and 77% and 69–84% with BUD/FORM and FORM, respectively, with an average 25% reduced risk of CID with BUD/FORM. All components contributed to the CID event rate. Experiencing a CID during the first 3 months was associated with poorer outcomes (lung function, quality of life, symptoms and reliever use) and increased risk of later CID events. The effect of BUD/FORM versus FORM in reducing CID risk was positively associated with the blood eosinophil count. CONCLUSIONS: Our findings suggest that BUD/FORM offers protective effects for CID events compared with FORM alone, with the magnitude of the effect dependent on patients’ eosinophil levels. CID may be an important tool for evaluation of treatment effect in a complex, multifaceted, and progressive disease like COPD, and a valuable tool to allow for shorter and smaller future outcome predictive trials in early drug development. BioMed Central 2020-01-10 2020 /pmc/articles/PMC6954504/ /pubmed/31924197 http://dx.doi.org/10.1186/s12931-020-1280-y Text en © The Author(s). 2020 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bafadhel, Mona
Singh, Dave
Jenkins, Christine
Peterson, Stefan
Bengtsson, Thomas
Wessman, Peter
Fagerås, Malin
Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
title Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
title_full Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
title_fullStr Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
title_full_unstemmed Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
title_short Reduced risk of clinically important deteriorations by ICS in COPD is eosinophil dependent: a pooled post-hoc analysis
title_sort reduced risk of clinically important deteriorations by ics in copd is eosinophil dependent: a pooled post-hoc analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954504/
https://www.ncbi.nlm.nih.gov/pubmed/31924197
http://dx.doi.org/10.1186/s12931-020-1280-y
work_keys_str_mv AT bafadhelmona reducedriskofclinicallyimportantdeteriorationsbyicsincopdiseosinophildependentapooledposthocanalysis
AT singhdave reducedriskofclinicallyimportantdeteriorationsbyicsincopdiseosinophildependentapooledposthocanalysis
AT jenkinschristine reducedriskofclinicallyimportantdeteriorationsbyicsincopdiseosinophildependentapooledposthocanalysis
AT petersonstefan reducedriskofclinicallyimportantdeteriorationsbyicsincopdiseosinophildependentapooledposthocanalysis
AT bengtssonthomas reducedriskofclinicallyimportantdeteriorationsbyicsincopdiseosinophildependentapooledposthocanalysis
AT wessmanpeter reducedriskofclinicallyimportantdeteriorationsbyicsincopdiseosinophildependentapooledposthocanalysis
AT fagerasmalin reducedriskofclinicallyimportantdeteriorationsbyicsincopdiseosinophildependentapooledposthocanalysis