Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD

FLAME Investigators, Uffe Bødtger (Member of author group)

Research output: Contribution to journalJournal articleResearchpeer-review

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.

Original languageEnglish
JournalThe New England Journal of Medicine
Volume374
Issue number23
Pages (from-to)2222-2234
ISSN1533-4406
DOIs
Publication statusPublished - 9. Jun 2016

Fingerprint

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

Keywords

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists/therapeutic use
  • Aged
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Fluticasone-Salmeterol Drug Combination/adverse effects
  • Glucocorticoids/therapeutic use
  • Glycopyrrolate/adverse effects
  • Humans
  • Indans/adverse effects
  • Male
  • Middle Aged
  • Muscarinic Antagonists/therapeutic use
  • Pulmonary Disease, Chronic Obstructive/drug therapy
  • Quinolones/adverse effects

Cite this

@article{f1115a729db64c44971df8e8b6fe866e,
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.",
keywords = "Administration, Inhalation, Adrenergic beta-2 Receptor Agonists/therapeutic use, Aged, Double-Blind Method, Drug Combinations, Female, Fluticasone-Salmeterol Drug Combination/adverse effects, Glucocorticoids/therapeutic use, Glycopyrrolate/adverse effects, Humans, Indans/adverse effects, Male, Middle Aged, Muscarinic Antagonists/therapeutic use, Pulmonary Disease, Chronic Obstructive/drug therapy, Quinolones/adverse effects",
author = "Wedzicha, {Jadwiga A} and Donald Banerji and Chapman, {Kenneth R} and J{\o}rgen Vestbo and Nicolas Roche and Timothy Ayers and Chau Thach and Robert Fogel and Francesco Patalano and Vogelmeier, {Claus F} and {FLAME Investigators} and Uffe B{\o}dtger",
year = "2016",
month = "6",
day = "9",
doi = "10.1056/NEJMoa1516385",
language = "English",
volume = "374",
pages = "2222--2234",
journal = "The New England Journal of Medicine",
issn = "0028-4793",
publisher = "Massachusetts Medical Society",
number = "23",

}

Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD. / FLAME Investigators ; Bødtger, Uffe (Member of author group).

In: The New England Journal of Medicine, Vol. 374, No. 23, 09.06.2016, p. 2222-2234.

Research output: Contribution to journalJournal articleResearchpeer-review

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, Timothy

AU - Thach, Chau

AU - Fogel, Robert

AU - Patalano, Francesco

AU - Vogelmeier, Claus F

AU - FLAME Investigators

A2 - Bødtger, Uffe

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.

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.

KW - Administration, Inhalation

KW - Adrenergic beta-2 Receptor Agonists/therapeutic use

KW - Aged

KW - Double-Blind Method

KW - Drug Combinations

KW - Female

KW - Fluticasone-Salmeterol Drug Combination/adverse effects

KW - Glucocorticoids/therapeutic use

KW - Glycopyrrolate/adverse effects

KW - Humans

KW - Indans/adverse effects

KW - Male

KW - Middle Aged

KW - Muscarinic Antagonists/therapeutic use

KW - Pulmonary Disease, Chronic Obstructive/drug therapy

KW - Quinolones/adverse effects

U2 - 10.1056/NEJMoa1516385

DO - 10.1056/NEJMoa1516385

M3 - Journal article

C2 - 27181606

VL - 374

SP - 2222

EP - 2234

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 23

ER -