RATE OF SEVERE COPD EXACERBATIONS WITH BUDESONIDE/GLYCOPYRRONIUM/FORMOTEROL FUMA-RATE DIHYDRATE METERED DOSE INHALER (BGF MDI) VERSUS DUAL THERAPIES: A POST-HOC SUBGROUP ANALYSIS OF THE ETHOS TRIAL

Introduction and Objectives The management of chronic obstructive pulmonary disease (COPD) exacerbations varies by region; in most countries, patients are hospitalized for serious or potentially life-threatening exacerbations only, while mild/moderate exacerbations are managed in general practice or outpatient settings. To determine whether regional differences had an impact on outcomes in the ETHOS study, we performed a post-hoc analysis of severe exacerbation rates in selected regions with similar management of COPD exacerbations. Methods ETHOS (NCT02465567) was a 52-week, randomized, double-blind study in patients with moderate-to-very severe COPD who had ≥1 moderate/severe exacerbation in the previous year. Patients received budesonide/glycopyrronium/formoterol fumarate dihydrate metered dose inhaler (BGF MDI) 320/14.4/10µg or 160/14.4/10μg; glycopyrronium/formoterol fumarate dihydrate (GFF) MDI 14.4/10µg; or budesonide/formoterol fumarate dihydrate (BFF) MDI 320/10µg. All treatments were administered twice-daily via an Aerosphere inhaler. This post-hoc analysis assessed the annualized rate of severe exacerbations (a secondary endpoint) in a subgroup of 23 countries with similar patient care practices, including all patients from Europe, North America, South America, Australia, New Zealand, and South Africa. Results The country subgroup population (n=7922) was a subset of the modified intent-to-treat (mITT) population (n=8509). In the global mITT population, BGF MDI 320/14.4/10µg significantly reduced the severe exacerbation rate by 20% versus BFF MDI (rate ratio [RR] 0.80 [95% CI 0.66–0.97], p=0.0221) with a numerical improvement of 16% versus GFF MDI (RR 0.84 [0.69–1.03], p=0.0944). In the country subgroup, BGF MDI 320/14.4/10µg significantly reduced severe exacerbations by 23% versus BFF MDI (RR 0.77 [95% CI 0.62–0.96], unadjusted p=0.0194); and by 20% versus GFF MDI (RR 0.80 [0.64–0.99], unadjusted p=0.0438). BGF MDI 160/14.4/10µg numerically improved severe exacerbation rates versus BFF MDI and GFF MDI (table 1). Conclusions In the 52-week ETHOS study, BGF MDI 320/14.4/10µg reduced the rate of severe exacerbations versus both BFF MDI and GFF MDI in a subset of 23 countries with similar patient care practices. The consistent risk reductions in this subset compared with the overall population support the benefits of BGF MDI 320/14.4/10µg compared with dual therapies in reducing the rate of exacerbations that require management in a hospital setting. Please refer to page A239 for declarations of interest related to this abstract.