Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD

Jadwiga A Wedzicha, Donald Banerji, Kenneth R Chapman, Jørgen Vestbo, Nicolas Roche, R Timothy Ayers, Chau Thach, Robert Fogel, Francesco Patalano, Claus F Vogelmeier, FLAME Investigators, Isa Cerveri

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Most guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.

METHODS: We conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.

RESULTS: A total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).

CONCLUSIONS: Indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.).

Original languageEnglish
Pages (from-to)2222-34
Number of pages13
JournalNew England Journal of Medicine
Volume374
Issue number23
DOIs
Publication statusPublished - Jun 9 2016

Fingerprint

Chronic Obstructive Pulmonary Disease
Confidence Intervals
Muscarinic Antagonists
Disease Progression
Glucocorticoids
indacaterol
Salmeterol Xinafoate Drug Combination Fluticasone Propionate
Incidence
Eosinophils
Inhalation
Pneumonia
Guidelines
Therapeutics

Keywords

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists
  • Aged
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Fluticasone Propionate, Salmeterol Xinafoate Drug Combination
  • Glucocorticoids
  • Glycopyrrolate
  • Humans
  • Indans
  • Male
  • Middle Aged
  • Muscarinic Antagonists
  • Pulmonary Disease, Chronic Obstructive
  • Quinolones
  • Comparative Study
  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

Cite this

Wedzicha, J. A., Banerji, D., Chapman, K. R., Vestbo, J., Roche, N., Ayers, R. T., ... Cerveri, I. (2016). Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. New England Journal of Medicine, 374(23), 2222-34. https://doi.org/10.1056/NEJMoa1516385

Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. / Wedzicha, Jadwiga A; Banerji, Donald; Chapman, Kenneth R; Vestbo, Jørgen; Roche, Nicolas; Ayers, R Timothy; Thach, Chau; Fogel, Robert; Patalano, Francesco; Vogelmeier, Claus F; FLAME Investigators ; Cerveri, Isa.

In: New England Journal of Medicine, Vol. 374, No. 23, 09.06.2016, p. 2222-34.

Research output: Contribution to journalArticle

Wedzicha, JA, Banerji, D, Chapman, KR, Vestbo, J, Roche, N, Ayers, RT, Thach, C, Fogel, R, Patalano, F, Vogelmeier, CF, FLAME Investigators & Cerveri, I 2016, 'Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD', New England Journal of Medicine, vol. 374, no. 23, pp. 2222-34. https://doi.org/10.1056/NEJMoa1516385
Wedzicha JA, Banerji D, Chapman KR, Vestbo J, Roche N, Ayers RT et al. Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. New England Journal of Medicine. 2016 Jun 9;374(23):2222-34. https://doi.org/10.1056/NEJMoa1516385
Wedzicha, Jadwiga A ; Banerji, Donald ; Chapman, Kenneth R ; Vestbo, Jørgen ; Roche, Nicolas ; Ayers, R Timothy ; Thach, Chau ; Fogel, Robert ; Patalano, Francesco ; Vogelmeier, Claus F ; FLAME Investigators ; Cerveri, Isa. / Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD. In: New England Journal of Medicine. 2016 ; Vol. 374, No. 23. pp. 2222-34.
@article{344f16441e4f4209b78dca8cc7ba97f1,
title = "Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD",
abstract = "BACKGROUND: Most guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.METHODS: We conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.RESULTS: A total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11{\%} lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95{\%} confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95{\%} CI, 60 to 82] vs. 51 days [95{\%} CI, 46 to 57]; hazard ratio, 0.84 [95{\%} CI, 0.78 to 0.91], representing a 16{\%} lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95{\%} CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95{\%} CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95{\%} CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2{\%} in the indacaterol-glycopyrronium group and 4.8{\%} in the salmeterol-fluticasone group (P=0.02).CONCLUSIONS: Indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.).",
keywords = "Administration, Inhalation, Adrenergic beta-2 Receptor Agonists, Aged, Double-Blind Method, Drug Combinations, Female, Fluticasone Propionate, Salmeterol Xinafoate Drug Combination, Glucocorticoids, Glycopyrrolate, Humans, Indans, Male, Middle Aged, Muscarinic Antagonists, Pulmonary Disease, Chronic Obstructive, Quinolones, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't",
author = "Wedzicha, {Jadwiga A} and Donald Banerji and Chapman, {Kenneth R} and J{\o}rgen Vestbo and Nicolas Roche and Ayers, {R Timothy} and Chau Thach and Robert Fogel and Francesco Patalano and Vogelmeier, {Claus F} and {FLAME Investigators} and Isa Cerveri",
year = "2016",
month = "6",
day = "9",
doi = "10.1056/NEJMoa1516385",
language = "English",
volume = "374",
pages = "2222--34",
journal = "New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachussetts Medical Society",
number = "23",

}

TY - JOUR

T1 - Indacaterol-Glycopyrronium versus Salmeterol-Fluticasone for COPD

AU - Wedzicha, Jadwiga A

AU - Banerji, Donald

AU - Chapman, Kenneth R

AU - Vestbo, Jørgen

AU - Roche, Nicolas

AU - Ayers, R Timothy

AU - Thach, Chau

AU - Fogel, Robert

AU - Patalano, Francesco

AU - Vogelmeier, Claus F

AU - FLAME Investigators

AU - Cerveri, Isa

PY - 2016/6/9

Y1 - 2016/6/9

N2 - BACKGROUND: Most guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.METHODS: We conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.RESULTS: A total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).CONCLUSIONS: Indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.).

AB - BACKGROUND: Most guidelines recommend either a long-acting beta-agonist (LABA) plus an inhaled glucocorticoid or a long-acting muscarinic antagonist (LAMA) as the first-choice treatment for patients with chronic obstructive pulmonary disease (COPD) who have a high risk of exacerbations. The role of treatment with a LABA-LAMA regimen in these patients is unclear.METHODS: We conducted a 52-week, randomized, double-blind, double-dummy, noninferiority trial. Patients who had COPD with a history of at least one exacerbation during the previous year were randomly assigned to receive, by inhalation, either the LABA indacaterol (110 μg) plus the LAMA glycopyrronium (50 μg) once daily or the LABA salmeterol (50 μg) plus the inhaled glucocorticoid fluticasone (500 μg) twice daily. The primary outcome was the annual rate of all COPD exacerbations.RESULTS: A total of 1680 patients were assigned to the indacaterol-glycopyrronium group, and 1682 to the salmeterol-fluticasone group. Indacaterol-glycopyrronium showed not only noninferiority but also superiority to salmeterol-fluticasone in reducing the annual rate of all COPD exacerbations; the rate was 11% lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (3.59 vs. 4.03; rate ratio, 0.89; 95% confidence interval [CI], 0.83 to 0.96; P=0.003). The indacaterol-glycopyrronium group had a longer time to the first exacerbation than did the salmeterol-fluticasone group (71 days [95% CI, 60 to 82] vs. 51 days [95% CI, 46 to 57]; hazard ratio, 0.84 [95% CI, 0.78 to 0.91], representing a 16% lower risk; P<0.001). The annual rate of moderate or severe exacerbations was lower in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (0.98 vs. 1.19; rate ratio, 0.83; 95% CI, 0.75 to 0.91; P<0.001), and the time to the first moderate or severe exacerbation was longer in the indacaterol-glycopyrronium group than in the salmeterol-fluticasone group (hazard ratio, 0.78; 95% CI, 0.70 to 0.86; P<0.001), as was the time to the first severe exacerbation (hazard ratio, 0.81; 95% CI, 0.66 to 1.00; P=0.046). The effect of indacaterol-glycopyrronium versus salmeterol-fluticasone on the rate of COPD exacerbations was independent of the baseline blood eosinophil count. The incidence of adverse events and deaths was similar in the two groups. The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).CONCLUSIONS: Indacaterol-glycopyrronium was more effective than salmeterol-fluticasone in preventing COPD exacerbations in patients with a history of exacerbation during the previous year. (Funded by Novartis; FLAME ClinicalTrials.gov number, NCT01782326.).

KW - Administration, Inhalation

KW - Adrenergic beta-2 Receptor Agonists

KW - Aged

KW - Double-Blind Method

KW - Drug Combinations

KW - Female

KW - Fluticasone Propionate, Salmeterol Xinafoate Drug Combination

KW - Glucocorticoids

KW - Glycopyrrolate

KW - Humans

KW - Indans

KW - Male

KW - Middle Aged

KW - Muscarinic Antagonists

KW - Pulmonary Disease, Chronic Obstructive

KW - Quinolones

KW - Comparative Study

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, Non-U.S. Gov't

U2 - 10.1056/NEJMoa1516385

DO - 10.1056/NEJMoa1516385

M3 - Article

VL - 374

SP - 2222

EP - 2234

JO - New England Journal of Medicine

JF - New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -