A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo

Joan B. Soriano; Don D. Sin; Xuekui Zhang; Pat G. Camp; Julie A. Anderson; Nick R. Anthonisen; A. Sonia Buist; P. Sherwood Burge; Peter M. Calverley; John E. Connett; Stefan Petersson; Dirkje S. Postma; Wojciech Szafranski; Jørgen Vestbo

doi:10.1378/chest.06-1696

A pooled analysis of FEV₁ decline in COPD patients randomized to inhaled corticosteroids or placebo

Joan B. Soriano, Don D. Sin, Xuekui Zhang, Pat G. Camp, Julie A. Anderson, Nick R. Anthonisen, A. Sonia Buist, P. Sherwood Burge, Peter M. Calverley, John E. Connett, Stefan Petersson, Dirkje S. Postma, Wojciech Szafranski, Jørgen Vestbo

Biostatistics

Research output: Contribution to journal › Article › peer-review

119 Scopus citations

Abstract

Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV₁. Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting ≥ 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV₁ decline in COPD patients, and whether this relationship is modified by gender and smoking. Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (± SE) relative increase in FEV ₁ of 2.42 ± 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV₁ decline (-0.01 ± 0.09%; p = 0.86). The initial treatment effect was dependent on smoMng status and gender. Smokers who continued to smoke had a smaller increase in FEV₁ during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV₁ with ICS therapy than did male ex-smokers. Conclusions: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV ₁ among those who completed these randomized clinical trials.

Original language	English (US)
Pages (from-to)	682-689
Number of pages	8
Journal	CHEST
Volume	131
Issue number	3
DOIs	https://doi.org/10.1378/chest.06-1696
State	Published - Mar 2007

Bibliographical note

Funding Information:
Dr. Soriano was an employee of GlaxoSmithKline, a manufacturer of respiratory drugs, up to 2005. Dr. Sin has received honoraria for speaking engagements from AstraZeneca and GlaxoSmithKline, and has received consultancy fees and research funding from GlaxoSmithKline. Dr. Anderson is currently an employee of GlaxoSmithKline, a manufacturer of respiratory drugs. Dr. Anthonisen and Dr. Buist are members of a respiratory advisory board for GlaxoSmithKline. Dr. Calverley has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Petersson is currently an employee of AstraZeneca, a manufacturer of respiratory drugs. Dr. Postma has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Vestbo has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Drs. Zhang, Camp, Burge, Connett, and Szafranski have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Funding Information:
Interdisciplinary Capacity Enhancement: Bridging Excellence in Respiratory Disease and Gender Studies (ICEBERGS), which is supported by funding from Canadian Institutes of Health Research (IGH/ICRH), the Canadian Lung Association, and the Heart and Stroke Foundation of Canada ( http://www.icebergs.ubc.ca ).

Keywords

COPD
Corticosteroids
FEV
Natural history
Pooled analysis

Publisher link

10.1378/chest.06-1696

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Soriano, J. B., Sin, D. D., Zhang, X., Camp, P. G., Anderson, J. A., Anthonisen, N. R., Buist, A. S., Burge, P. S., Calverley, P. M., Connett, J. E., Petersson, S., Postma, D. S., Szafranski, W., & Vestbo, J. (2007). A pooled analysis of FEV₁ decline in COPD patients randomized to inhaled corticosteroids or placebo. CHEST, 131(3), 682-689. https://doi.org/10.1378/chest.06-1696

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abstract = "Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1. Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting ≥ 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV1 decline in COPD patients, and whether this relationship is modified by gender and smoking. Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (± SE) relative increase in FEV 1 of 2.42 ± 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV1 decline (-0.01 ± 0.09%; p = 0.86). The initial treatment effect was dependent on smoMng status and gender. Smokers who continued to smoke had a smaller increase in FEV1 during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV1 with ICS therapy than did male ex-smokers. Conclusions: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV 1 among those who completed these randomized clinical trials.",

keywords = "COPD, Corticosteroids, FEV, Natural history, Pooled analysis",

author = "Soriano, {Joan B.} and Sin, {Don D.} and Xuekui Zhang and Camp, {Pat G.} and Anderson, {Julie A.} and Anthonisen, {Nick R.} and Buist, {A. Sonia} and Burge, {P. Sherwood} and Calverley, {Peter M.} and Connett, {John E.} and Stefan Petersson and Postma, {Dirkje S.} and Wojciech Szafranski and J{\o}rgen Vestbo",

note = "Funding Information: Dr. Soriano was an employee of GlaxoSmithKline, a manufacturer of respiratory drugs, up to 2005. Dr. Sin has received honoraria for speaking engagements from AstraZeneca and GlaxoSmithKline, and has received consultancy fees and research funding from GlaxoSmithKline. Dr. Anderson is currently an employee of GlaxoSmithKline, a manufacturer of respiratory drugs. Dr. Anthonisen and Dr. Buist are members of a respiratory advisory board for GlaxoSmithKline. Dr. Calverley has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Petersson is currently an employee of AstraZeneca, a manufacturer of respiratory drugs. Dr. Postma has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Vestbo has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Drs. Zhang, Camp, Burge, Connett, and Szafranski have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Funding Information: Interdisciplinary Capacity Enhancement: Bridging Excellence in Respiratory Disease and Gender Studies (ICEBERGS), which is supported by funding from Canadian Institutes of Health Research (IGH/ICRH), the Canadian Lung Association, and the Heart and Stroke Foundation of Canada ( http://www.icebergs.ubc.ca ). ",

year = "2007",

month = mar,

doi = "10.1378/chest.06-1696",

language = "English (US)",

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publisher = "American College of Chest Physicians",

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T1 - A pooled analysis of FEV1 decline in COPD patients randomized to inhaled corticosteroids or placebo

AU - Soriano, Joan B.

AU - Sin, Don D.

AU - Zhang, Xuekui

AU - Camp, Pat G.

AU - Anderson, Julie A.

AU - Anthonisen, Nick R.

AU - Buist, A. Sonia

AU - Burge, P. Sherwood

AU - Calverley, Peter M.

AU - Connett, John E.

AU - Petersson, Stefan

AU - Postma, Dirkje S.

AU - Szafranski, Wojciech

AU - Vestbo, Jørgen

N1 - Funding Information: Dr. Soriano was an employee of GlaxoSmithKline, a manufacturer of respiratory drugs, up to 2005. Dr. Sin has received honoraria for speaking engagements from AstraZeneca and GlaxoSmithKline, and has received consultancy fees and research funding from GlaxoSmithKline. Dr. Anderson is currently an employee of GlaxoSmithKline, a manufacturer of respiratory drugs. Dr. Anthonisen and Dr. Buist are members of a respiratory advisory board for GlaxoSmithKline. Dr. Calverley has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Petersson is currently an employee of AstraZeneca, a manufacturer of respiratory drugs. Dr. Postma has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Dr. Vestbo has received honoraria for speaking engagements and research funding from AstraZeneca and GlaxoSmithKline. Drs. Zhang, Camp, Burge, Connett, and Szafranski have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. Funding Information: Interdisciplinary Capacity Enhancement: Bridging Excellence in Respiratory Disease and Gender Studies (ICEBERGS), which is supported by funding from Canadian Institutes of Health Research (IGH/ICRH), the Canadian Lung Association, and the Heart and Stroke Foundation of Canada ( http://www.icebergs.ubc.ca ).

PY - 2007/3

Y1 - 2007/3

N2 - Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1. Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting ≥ 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV1 decline in COPD patients, and whether this relationship is modified by gender and smoking. Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (± SE) relative increase in FEV 1 of 2.42 ± 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV1 decline (-0.01 ± 0.09%; p = 0.86). The initial treatment effect was dependent on smoMng status and gender. Smokers who continued to smoke had a smaller increase in FEV1 during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV1 with ICS therapy than did male ex-smokers. Conclusions: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV 1 among those who completed these randomized clinical trials.

AB - Background: There is controversy about whether therapy with inhaled corticosteroids (ICSs) modifies the natural history of COPD, characterized by an accelerated decline in FEV1. Methods: The Inhaled Steroids Effect Evaluation in COPD (ISEEC) study is a pooled study of patient-level data from seven long-term randomized controlled trials of ICS vs placebo lasting ≥ 12 months in patients with moderate-to-severe COPD. We have previously reported a survival benefit for ICS therapy in COPD patients using ISEEC data. We aimed to determine whether the regular use of ICSs vs placebo improves FEV1 decline in COPD patients, and whether this relationship is modified by gender and smoking. Results: There were 3,911 randomized participants (29.2% female) in this analysis. In the first 6 months after randomization, ICS use was associated with a significant mean (± SE) relative increase in FEV 1 of 2.42 ± 0.19% compared with placebo (p < 0.01), which is quantifiable in absolute terms as 42 mL in men and 29 mL in women over 6 months. From 6 to 36 months, there was no significant difference between placebo and ICS therapy in terms of FEV1 decline (-0.01 ± 0.09%; p = 0.86). The initial treatment effect was dependent on smoMng status and gender. Smokers who continued to smoke had a smaller increase in FEV1 during the first 6 months than did ex-smokers. Female ex-smokers had a larger increase in FEV1 with ICS therapy than did male ex-smokers. Conclusions: We conclude that in COPD in the first 6 months of treatment, ICS therapy is more effective in ex-smokers than in current smokers with COPD in improving lung function, and women may have a bigger response to ICSs than men. However, it seems that after 6 months, ICS therapy does not modify the decline in FEV 1 among those who completed these randomized clinical trials.

KW - COPD

KW - Corticosteroids

KW - FEV

KW - Natural history

KW - Pooled analysis

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