Top

Published in:

Open Access 01-12-2018 | Research

Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study

Authors: Antonio R. Anzueto, Konstantinos Kostikas, Karen Mezzi, Steven Shen, Michael Larbig, Francesco Patalano, Robert Fogel, Donald Banerji, Jadwiga A. Wedzicha

Published in: Respiratory Research | Issue 1/2018

Abstract

Background

Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening. This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.

Methods

CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV₁) or ≥ 4-unit increase in St. George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation. Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.

Results

IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67–0.78]; P < 0.0001), and reduced the incidences of CID versus SFC. Additionally, IND/GLY delayed the time to CID in all patient subgroups. After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001). CID+ patients had a comparable change in the SGRQ total score versus CID− patients.

Conclusions

IND/GLY reduced the risk of CID versus SFC. CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.

Trial registration

Clinicaltrials.gov NCT01782326.

Available only for authorised users

Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management. In: And prevention of chronic obstructive pulmonary disease; 2018.

Adeloye D, Chua S, Lee C, Basquill C, Papana A, Theodoratou E, Nair H, Gasevic D, Sridhar D, Campbell H, et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J Glob Health. 2015;5:020415.CrossRefPubMedPubMedCentral

Wedzicha JA, Decramer M, Ficker JH, Niewoehner DE, Sandstrom T, Taylor AF, D'Andrea P, Arrasate C, Chen H, Banerji D. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, double-blind, parallel-group study. Lancet Respir Med. 2013;1:199–209.CrossRefPubMed

Vogelmeier CF, Gaga M, Aalamian-Mattheis M, Greulich T, Marin JM, Castellani W, Ninane V, Lane S, Nunez X, Patalano F, et al. Efficacy and safety of direct switch to indacaterol/glycopyrronium in patients with moderate COPD: the CRYSTAL open-label randomised trial. Respir Res. 2017;18:140.CrossRefPubMedPubMedCentral

Anzueto AR, Vogelmeier CF, Kostikas K, Mezzi K, Fucile S, Bader G, Shen S, Banerji D, Fogel R. The effect of indacaterol/glycopyrronium versus tiotropium or salmeterol/fluticasone on the prevention of clinically important deterioration in COPD. Int J Chron Obstruct Pulmon Dis. 2017;12:1325–37.CrossRefPubMedPubMedCentral

Singh D, Maleki-Yazdi MR, Tombs L, Iqbal A, Fahy WA, Naya I. Prevention of clinically important deteriorations in COPD with umeclidinium/vilanterol. Int J Chron Obstruct Pulmon Dis. 2016;11:1413–24.CrossRefPubMedPubMedCentral

Maleki-Yazdi MR, Singh D, Anzueto A, Tombs L, Fahy WA, Naya I. Assessing short-term deterioration in maintenance-naive patients with COPD receiving umeclidinium/vilanterol and tiotropium: a pooled analysis of three randomized trials. Adv Ther. 2017;33:2188–99.CrossRefPubMed

Bateman ED, Ferguson GT, Barnes N, Gallagher N, Green Y, Henley M, Banerji D. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J. 2013;42:1484–94.CrossRefPubMedPubMedCentral

Mahler DA, Decramer M, D'Urzo A, Worth H, White T, Alagappan VK, Chen H, Gallagher N, Kulich K, Banerji D. Dual bronchodilation with QVA149 reduces patient-reported dyspnoea in COPD: the BLAZE study. Eur Respir J. 2014;43:1599–609.CrossRefPubMed

10.

Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT, Thach C, Fogel R, Patalano F, Vogelmeier CF. Indacaterol-glycopyrronium versus salmeterol-fluticasone for COPD. N Engl J Med. 2016;374:2222–34.CrossRefPubMed

11.

Vogelmeier CF, Bateman ED, Pallante J, Alagappan VK, D'Andrea P, Chen H, Banerji D. Efficacy and safety of once-daily QVA149 compared with twice-daily salmeterol-fluticasone in patients with chronic obstructive pulmonary disease (ILLUMINATE): a randomised, double-blind, parallel group study. Lancet Respir Med. 2013;(1):51–60.

12.

Tomlinson G, Detsky AS. Composite end points in randomized trials: there is no free lunch. JAMA. 2010;303:267–8.CrossRefPubMed

13.

Ferreira-Gonzalez I, Permanyer-Miralda G, Busse JW, Bryant DM, Montori VM, Alonso-Coello P, Walter SD, Guyatt GH. Methodologic discussions for using and interpreting composite endpoints are limited, but still identify major concerns. J Clin Epidemiol. 2007;60:651–7.CrossRefPubMed

14.

Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, Pinto Plata V, Cabral HJ. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. N Engl J Med. 2004;350:1005–12.CrossRefPubMed

15.

Jones RC, Donaldson GC, Chavannes NH, Kida K, Dickson-Spillmann M, Harding S, Wedzicha JA, Price D, Hyland ME. Derivation and validation of a composite index of severity in chronic obstructive pulmonary disease: the DOSE index. Am J Respir Crit Care Med. 2009;180:1189–95.CrossRefPubMed

16.

Puhan MA, Garcia-Aymerich J, Frey M, ter Riet G, Anto JM, Agusti AG, Gomez FP, Rodriguez-Roisin R, Moons KG, Kessels AG, Held U. Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: the updated BODE index and the ADO index. Lancet. 2009;374:704–11.CrossRefPubMed

17.

Stolz D, Kostikas K, Blasi F, Boersma W, Milenkovic B, Lacoma A, Louis R, Aerts JG, Welte T, Torres A, et al. Adrenomedullin refines mortality prediction by the BODE index in COPD: the "BODE-A" index. Eur Respir J. 2014;43:397–408.CrossRefPubMed

18.

Boeck L, Soriano JB, Brusse-Keizer M, Blasi F, Kostikas K, Boersma W, Milenkovic B, Louis R, Lacoma A, Djamin R, et al. Prognostic assessment in COPD without lung function: the B-AE-D indices. Eur Respir J. 2016;47:1635–44.CrossRefPubMedPubMedCentral

19.

Roche N, Chapman KR, Vogelmeier CF, Herth FJF, Thach C, Fogel R, Olsson P, Patalano F, Banerji D, Wedzicha JA. Blood eosinophils and response to maintenance chronic obstructive pulmonary disease treatment. Data from the FLAME trial. Am J Respir Crit Care Med. 2017;195:1189–97.CrossRefPubMed

20.

Ferguson GT, Karpel JP, Clerisme-Beaty E, Gronke L, Voss F, Buhl R. Efficacy and safety of tiotropium + olodaterol maintenance treatment in patients with COPD in the TONADO((R)) and OTEMTO((R)) studies: a subgroup analysis by age. Int J Chron Obstruct Pulmon Dis. 2016;11:2701–10.CrossRefPubMedPubMedCentral

21.

Tsiligianni I, Mezzi K, Fucile S, Kostikas K, Shen S, Banerji D, Fogel R. Response to Indacaterol/Glycopyrronium (IND/GLY) by sex in patients with COPD: a pooled analysis from the IGNITE program. COPD. 2017;14:375–81.CrossRefPubMed

22.

Jones PW, Gelhorn H, Karlsson N, Menjoge S, Mullerova H, Rennard SI, Tal-Singer R, Wilson H, Merrill D, Tabberer M. Baseline severity as predictor of change in St George's respiratory questionnaire scores in trials of long-acting bronchodilators with COPD patients. Chronic Obstr Pulm Dis. 2017;4:132–40.PubMedPubMedCentral

23.

Bafadhel M, Peterson S, De Blas MA, Calverley PM, Rennard SI, Richter K, Fageras M. Predictors of exacerbation risk and response to budesonide in patients with chronic obstructive pulmonary disease: a post-hoc analysis of three randomised trials. Lancet Respir Med. 2018;6(2):117–26.

24.

Papi A, Kostikas K, Wedzicha JA, Vogelmeier CF, Roche N, Shen S, Banerji D, Fogel R, Patalano F, Chapman KR. Dual bronchodilation response by exacerbation history and eosinophilia in the FLAME study. Am J Respir Crit Care Med.2018;197(9):1223–6.

25.

Donaldson GC, Seemungal TA, Bhowmik A, Wedzicha JA. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2002;57:847–52.CrossRefPubMedPubMedCentral

26.

Naya I, Tombs L, Mullerova H, Compton C, Jones P. Long-term outcome following first clinically important deterioration in COPD. Eur Respir J. 2016;(48):PA304.

27.

Magnussen H, Disse B, Rodriguez-Roisin R, Kirsten A, Watz H, Tetzlaff K, Towse L, Finnigan H, Dahl R, Decramer M, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N Engl J Med. 2014;371:1285–94.CrossRefPubMed

28.

Ford I, Norrie J. Pragmatic trials. N Engl J Med. 2016;375:454–63.CrossRefPubMed

Title: Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study
Authors: Antonio R. Anzueto
Konstantinos Kostikas
Karen Mezzi
Steven Shen
Michael Larbig
Francesco Patalano
Robert Fogel
Donald Banerji
Jadwiga A. Wedzicha
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2018
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-018-0830-z

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Indacaterol/glycopyrronium versus salmeterol/fluticasone in the prevention of clinically important deterioration in COPD: results from the FLAME study

Abstract

Background

Methods

Results

Conclusions

Trial registration

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2018

Uric acid, lung function, physical capacity and exacerbation frequency in patients with COPD: a multi-dimensional approach

Selective activation and proliferation of a quiescent stem cell population in the neuroepithelial body microenvironment

Single-inhaler fluticasone furoate/umeclidinium/vilanterol versus fluticasone furoate/vilanterol plus umeclidinium using two inhalers for chronic obstructive pulmonary disease: a randomized non-inferiority study

Epithelial mesenchymal transition (EMT): a universal process in lung diseases with implications for cystic fibrosis pathophysiology

A role for telomere length and chromosomal damage in idiopathic pulmonary fibrosis

Identification of deleterious and regulatory genomic variations in known asthma loci

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page