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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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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 |
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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 |
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