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

Shigeo Muro,1 Munehiro Seki,2 John R Hurst,3 David Petullo,4 Jonathan Marshall,5 Karin Bowen,4 Patrick F Darken,4 Elizabeth A Duncan,6 Ayman Megally,4 Mehul Patel5 1Department of Respiratory Medicine, Nara Medical University, Nara, Japan; 2AstraZeneca K.K., Osaka, Japan; 3UCL Respiratory, University College London, London, UK; 4AstraZeneca, Gaithersburg, MD, USA; 5AstraZeneca, Cambridge, UK; 6AstraZeneca, Durham, NC, USACorrespondence: Mehul Patel, AstraZeneca, Academy House, 136 hills Road, Cambridge, CB2 8PA, UK, Email [email protected]: 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: asthma, budesonide/glycopyrronium/formoterol fumarate dihydrate, COPD, exacerbation, health-related quality of life, lung function