Triple Therapy with Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate versus Dual Therapies for Patients with COPD and Phenotypic Features of Asthma: A Pooled Post Hoc Analysis of KRONOS and ETHOS

Int J Chron Obstruct Pulmon Dis. 2024 Dec 12:19:2729-2737. doi: 10.2147/COPD.S478349. eCollection 2024.

Abstract

Background: We evaluated the inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β2-agonist (ICS/LAMA/LABA) triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual LAMA/LABA and ICS/LABA therapies in patients with chronic obstructive pulmonary disease (COPD) and phenotypic features of asthma (bronchodilator reversibility and elevated blood eosinophils), but no asthma diagnosis, for whom treatment guidelines are limited.

Patients and methods: KRONOS (NCT02497001) and ETHOS (NCT02465567) enrolled patients with moderate-to-very-severe COPD, no current asthma diagnosis, and either ≥0 (KRONOS) or ≥1 (ETHOS) moderate/severe exacerbations in the prior year. This pooled post hoc analysis evaluated trough forced expiratory volume in 1 second (FEV1) and FEV1 area under the curve from hours 0 to 4 (AUC0-4) change from baseline over 12-24 weeks, moderate/severe exacerbation rates, and St George's Respiratory Questionnaire (SGRQ) total score over 24 weeks with ICS/LAMA/LABA (BGF 320/14.4/10 µg), LAMA/LABA (glycopyrronium/formoterol fumarate dihydrate [GFF] 14.4/10 µg), and ICS/LABA (budesonide/formoterol fumarate dihydrate [BFF] 320/10 µg) in patients with phenotypic features of asthma defined as reversibility to salbutamol and blood eosinophils ≥300 cells/mm3. Analyses were not adjusted for multiplicity.

Results: BGF improved trough FEV1 and FEV1 AUC0-4 versus GFF (least squares mean [LSM] difference [95% confidence interval (CI)] 125 [39-211] and 153 [59-247] mL) and BFF (LSM difference [95% CI] 118 [30-207] and 146 [49-243] mL). Exacerbation rates were estimated to be lower with BGF versus GFF and BFF (respective rate ratios [95% CI] 0.28 [0.19-0.43] and 0.69 [0.45-1.05]) and SGRQ total score was estimated to be improved with BGF versus GFF and BFF (respective LSM differences [95% CI] -5.18 [-8.11 to -2.24] and -1.09 [-4.08 to 1.91]).

Conclusion: BGF was estimated to have benefits on lung function, exacerbations, and health-related quality of life versus dual therapies in patients with COPD and phenotypic features of asthma.

Trial registration: ClinicalTrials.gov NCT02497001 and NCT02465567.

Keywords: COPD; asthma; budesonide/glycopyrronium/formoterol fumarate dihydrate; exacerbation; health-related quality of life; lung function.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists* / administration & dosage
  • Adrenergic beta-2 Receptor Agonists* / adverse effects
  • Aged
  • Asthma* / diagnosis
  • Asthma* / drug therapy
  • Asthma* / physiopathology
  • Bronchodilator Agents* / administration & dosage
  • Bronchodilator Agents* / adverse effects
  • Budesonide / administration & dosage
  • Budesonide, Formoterol Fumarate Drug Combination / administration & dosage
  • Disease Progression
  • Drug Combinations
  • Drug Therapy, Combination
  • Female
  • Forced Expiratory Volume
  • Formoterol Fumarate / administration & dosage
  • Glycopyrrolate* / administration & dosage
  • Glycopyrrolate* / adverse effects
  • Humans
  • Lung* / drug effects
  • Lung* / physiopathology
  • Male
  • Middle Aged
  • Muscarinic Antagonists* / administration & dosage
  • Muscarinic Antagonists* / adverse effects
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive* / diagnosis
  • Pulmonary Disease, Chronic Obstructive* / drug therapy
  • Pulmonary Disease, Chronic Obstructive* / physiopathology
  • Recovery of Function
  • Severity of Illness Index
  • Time Factors
  • Treatment Outcome

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Bronchodilator Agents
  • Budesonide
  • Budesonide, Formoterol Fumarate Drug Combination
  • Drug Combinations
  • Formoterol Fumarate
  • Glycopyrrolate
  • Muscarinic Antagonists

Associated data

  • ClinicalTrials.gov/NCT02465567
  • ClinicalTrials.gov/NCT02497001

Grants and funding

This analysis and the ETHOS and KRONOS studies were sponsored by AstraZeneca.