Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • For authors
    • Instructions for authors
    • Submit a manuscript
    • Author FAQs
    • Open access
    • COVID-19 submission information
  • Alerts
  • Podcasts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • For authors
    • Instructions for authors
    • Submit a manuscript
    • Author FAQs
    • Open access
    • COVID-19 submission information
  • Alerts
  • Podcasts
  • Subscriptions

Regional differences in rate of FEV1 decline in COPD: lessons from SUMMIT

Bartolomé R. Celli, Julie A. Anderson, Robert D. Brook, Peter M.A. Calverley, Nicholas J. Cowans, Courtney Crim, Fernando Martinez, David E. Newby, Julie Yates, Jørgen Vestbo
European Respiratory Journal 2019 53: 1900278; DOI: 10.1183/13993003.00278-2019
Bartolomé R. Celli
1Pulmonary and Critical Care Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bartolomé R. Celli
  • For correspondence: bcelli@copdnet.org
Julie A. Anderson
2Research and Development, GlaxoSmithKline, Stockley Park, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Julie A. Anderson
Robert D. Brook
3University of Michigan Health System, Ann Arbor, MI, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter M.A. Calverley
4Dept of Medicine, Clinical Sciences Centre, University of Liverpool, University Hospital Aintree, Liverpool, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nicholas J. Cowans
5Statistics and Programming, Veramed Ltd, Twickenham, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Courtney Crim
6Research and Development, GlaxoSmithKline, Research Triangle Park, North Carolina, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fernando Martinez
7Division of Pulmonary and Critical Care Medicine, Weill Cornell Medicine, New York, NY, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David E. Newby
8Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Julie Yates
6Research and Development, GlaxoSmithKline, Research Triangle Park, North Carolina, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jørgen Vestbo
9Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, University of Manchester, and Manchester University NHS Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

This analysis of FEV1 decline in patients who enrolled with spirometric GOLD stage II COPD (SUMMIT) showed regional differences in therapeutic response. Such variation should be considered when comparing pharmacotherapies across different global areas. http://bit.ly/2YwMIgW

To the Editor:

A publication by Zhou et al. [1], who studied 841 patients from China with mild to moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I and II) for 2 years, documented a 22 mL per year beneficial effect of tiotropium compared with placebo on rate of forced expiratory volume in 1 s (FEV1). This effect was over three times larger than the 6 mL per year (95% CI 1 to 11 mL per year) reported by Decramer et al. [2] in the 2739 GOLD stage II patients from the 4-year UPLIFT trial. We hypothesised that the large difference in results in patients with COPD with similar degree of airflow limitation at study entry could be related to regional differences in response to similar pharmacological treatment. To test this hypothesis, we investigated the regional differences in FEV1 decline in patients in the COPD Study to Understand Mortality and MorbidITy (SUMMIT), all of whom had spirometric GOLD stage II COPD at enrolment [3].

In SUMMIT, we investigated whether the inhaled corticosteroid fluticasone furoate 100 μg (FF), the long-acting beta-agonist vilanterol 25 µg (VI) or the combination (FF/VI) impacted on mortality. The results from this event-driven study failed to show a benefit of any of the medications on risk of death compared with placebo [3]. In addition, and as secondary pre-specified outcome, spirometry was measured every 12 weeks. Results of the effect of therapy on lung function decline for the whole SUMMIT cohort has been published [4], which included 15 457 patients with an average of seven spirometry assessments who were followed for an average of 1.7 years. This did not compare regional differences, so here we have performed a post hoc analysis using the same methods but with subjects divided into Asia and non-Asia subgroups. We present only patients taking placebo or FF/VI for brevity.

In SUMMIT, there were 1337 patients randomised to placebo or FF/VI in the Asia subgroup (China, Indonesia, India, Japan, Korea, Malaysia, Philippines, Taiwan, Thailand and Vietnam), of which 253 were from China. As shown in table 1, the rate of FEV1 decline in this subgroup was 16 mL per year (95% CI −1 to 34 mL per year), slower on active FF/VI therapy than on placebo. This value is close to that reported by Zhou et al. [1] in their study, which was 22 mL per year (95% CI 6 to 37) favouring tiotropium over placebo. In contrast, in the 8232 patients that were not from Asia studied in SUMMIT, a 7 mL per year (95% CI −1 to 14 mL per year) difference was seen for FF/VI versus placebo.

View this table:
  • View inline
  • View popup
TABLE 1

Clinical characteristics and lung function decline in Asians compared with non-Asians in two different pharmacological trials

Table 1 also shows that this regional effect remains when the values are expressed as per cent predicted FEV1 in both the Zhou et al. [1] and SUMMIT Asia subpopulations. In the former study, a difference of 0.9% per year was seen for tiotropium versus placebo. In the SUMMIT Asia subgroup, this was 0.7% per year (95% CI −0.1 to 1.4% per year), whereas in the non-Asian SUMMIT patients taking FF/VI had a slower decline of 0.2% per year (95% CI 0.0 to 0.5% per year) compared with placebo.

To our knowledge, no study has reported the potential effect of regional response to medications as a possible determinant of lung function decline. The results observed suggests that there are regional differences in the response to pharmacotherapy. In the patients recruited in China by Zhou et al. [1] and in Asia in SUMMIT (table 1), the effect of pharmacotherapy, independent of the medication used, was at least double of that observed in non-Asian countries.

One potential explanation is that the patients had higher baseline FEV1 value in mL in the Zhou et al. [1] cohort compared with the patients recruited in SUMMIT. However, the absolute rate of decline in the placebo group in the SUMMIT Asian population (table 1) was, if anything, higher (56 mL per year) than that of the placebo group in the Zhou study (51 mL per year). Further, when expressed as a proportion of FEV1 change (to normalise for baseline FEV1 value) the difference still remained between the Asian and the non-Asian groups. It may also be that there were differences in the therapy that patients were receiving at baseline. However, the criteria for inclusion in SUMMIT was similar across regions. In addition, as was true for the study by Zhou et al. [1], the majority of patients had milder disease for which medications are least used. Other potential reasons such as differences in body mass index or environmental exposure remain to be explored.

We believe these findings are not only interesting but important because regional differences in response to therapy should be taken into account when comparing effects of therapeutic agents in different areas of the world. Why different populations behave in this way merits further study.

These analyses add to the growing evidence that pharmacotherapy does modify lung function progression in COPD and, as such, a nihilistic approach to the benefit of pharmacotherapy is not justified.

Footnotes

  • Support statement: The SUMMIT study (GSK study number 113782; NCT01313676) was funded by GSK. Funding information for this article has been deposited with the Crossref Funder Registry.

  • Conflict of interest: B.R. Celli reports grants from AstraZeneca, personal fees for consultancy from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca and Novartis, personal fees for travel from GlaxoSmithKline, personal fees for participating in review activities from GlaxoSmithKline, during the conduct of the study; personal fees for consultancy from Boehringer Ingelheim, AstraZeneca, Almirall and Novartis, outside the submitted work.

  • Conflict of interest: J.A. Anderson is an employee of and owns shares in GSK.

  • Conflict of interest: R.D. Brook reports personal fees for steering committee work from GSK, during the conduct of the study.

  • Conflict of interest: P.M.A. Calverley has advised Boehringer Ingelheim, GSK, AstraZeneca and Takeda on the design and conduct of clinical trials and has spoken at meetings sponsored by these companies and by Novartis. He has no stock holdings in any pharmaceutical company or connection with the tobacco industry.

  • Conflict of interest: N.J. Cowans is employed by Veramed Ltd, a contract research organisation undertaking contracted statistical analyses of respiratory studies funded by GSK.

  • Conflict of interest: C. Crim is an employee of and owns shares in GSK.

  • Conflict of interest: F. Martinez reports non-financial support from GSK as sponsor of the parent study; personal fees for organising education from Continuing Education, CME Incite, Annenberg Center for Health Sciences at Eisenhower, Integritas, Paradigm Medical Communications, LLC, PeerVoice, UpToDate, Haymarket Communications, Western Society of Allergy and Immunology, Methodist Hospital, Columbia University, Prime Healthcare Ltd, WebMD, PeerView Network, California Society of Allergy and Immunology, National Association for Continuing Education, Chiesi and Puerto Rico Thoracic Society, personal fees for steering committee work from Forest Laboratories, has participating on an advisory board for Janssen, personal fees for steering committee, data and safety monitoring board and advisory board work, and lecturing from GlaxoSmithKline, personal fees for steering committee and advisory board work, and organising education from Nycomed/Takeda, personal fees for steering committee and advisory board work, and lecturing from AstraZeneca and Boehringer Ingelheim, personal fees for advisory board work from Bellerophon (formerly Ikaria), Genentech, Roche, Sunovion, Theravance and ConCert Pharmaceuticals, personal fees for advisory board work and organising education from Novartis, personal fees for steering committee and advisory board work from Pearl, personal fees for consultancy from InThought, Proterixbio (formerly Bioscale), Unity Biotechnology and Lucid, outside the submitted work.

  • Conflict of interest: D.E. Newby reports grants and personal fees for steering committee work from GSK, during the conduct of the study.

  • Conflict of interest: J. Yates is an employee of and owns shares in GSK.

  • Conflict of interest: J. Vestbo reports personal fees for steering committee work from GlaxoSmithKline, during the conduct of the study; personal fees from for consultancy and lecturing from GlaxoSmithKline, Chiesi Pharmaceuticals, Boehringer Ingelheim, Novartis and AstraZeneca, outside the submitted work.

  • The SUMMIT trial is a registered clinical trial (NCT01313676). Information on GSK's data sharing commitments and requesting access to anonymised individual participant data and associated documents can be found at www.clinicalstudydatarequest.com

  • Received February 8, 2019.
  • Accepted March 3, 2019.
  • Copyright ©ERS 2019
https://www.ersjournals.com/user-licence

References

  1. ↵
    1. Zhou Y,
    2. Zhong NS,
    3. Li X, et al.
    Tiotropium in early-stage chronic obstructive pulmonary disease. N Engl J Med 2017; 377: 923–935.
    OpenUrlCrossRefPubMed
  2. ↵
    1. Decramer M,
    2. Celli B,
    3. Kesten S, et al.
    Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet 2009; 374: 1171–1178.
    OpenUrlCrossRefPubMedWeb of Science
  3. ↵
    1. Vestbo J,
    2. Anderson JA,
    3. Brook RD, et al.
    Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet 2016; 387: 1817–1826.
    OpenUrlPubMed
  4. ↵
    1. Calverley PMA,
    2. Anderson JA,
    3. Brook RD, et al.
    Fluticasone furoate, vilanterol and lung function decline in patients with moderate chronic obstructive pulmonary disease and heightened cardiovascular risk. Am J Respir Crit Care Med 2018; 197: 47–55.
    OpenUrl
    1. Hankinson JL,
    2. Kawut SM,
    3. Shahar E, et al.
    Performance of American Thoracic Society-recommended spirometry reference values in a multiethnic sample of adults: the multi-ethnic study of atherosclerosis (MESA) lung study. Chest 2010; 137: 138–145.
    OpenUrlCrossRefPubMedWeb of Science
PreviousNext
Back to top
View this article with LENS
Vol 53 Issue 6 Table of Contents
European Respiratory Journal: 53 (6)
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Regional differences in rate of FEV1 decline in COPD: lessons from SUMMIT
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
Alerts
Sign In to Email Alerts with your Email Address
Citation Tools
Regional differences in rate of FEV1 decline in COPD: lessons from SUMMIT
Bartolomé R. Celli, Julie A. Anderson, Robert D. Brook, Peter M.A. Calverley, Nicholas J. Cowans, Courtney Crim, Fernando Martinez, David E. Newby, Julie Yates, Jørgen Vestbo
European Respiratory Journal Jun 2019, 53 (6) 1900278; DOI: 10.1183/13993003.00278-2019

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Regional differences in rate of FEV1 decline in COPD: lessons from SUMMIT
Bartolomé R. Celli, Julie A. Anderson, Robert D. Brook, Peter M.A. Calverley, Nicholas J. Cowans, Courtney Crim, Fernando Martinez, David E. Newby, Julie Yates, Jørgen Vestbo
European Respiratory Journal Jun 2019, 53 (6) 1900278; DOI: 10.1183/13993003.00278-2019
del.icio.us logo Digg logo Reddit logo Technorati logo Twitter logo CiteULike logo Connotea logo Facebook logo Google logo Mendeley logo
Full Text (PDF)

Jump To

  • Article
    • Abstract
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

Agora

  • Leukocyte telomere length and mycophenolate therapy in CHP
  • Connexins and the pulmonary vascular response to hypoxia
  • Fixed breathing protocols in multiple-breath washout testing in children
Show more Agora

Research letters

  • Leukocyte telomere length and mycophenolate therapy in CHP
  • Connexins and the pulmonary vascular response to hypoxia
  • Fixed breathing protocols in multiple-breath washout testing in children
Show more Research letters

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Reviewers
  • CME
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Submit a manuscript
  • ERS author centre

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2021 by the European Respiratory Society