Seasonal variation in COPD exacerbation rates: budesonide/glycopyrronium/formoterol metered dose inhaler (BGF MDI) at two ICS dose levels in the ETHOS trial

Background: In the Phase III, 52-week ETHOS study (NCT02465567), BGF MDI triple fixed-dose combination, reduced moderate/severe COPD exacerbation rate vs. dual therapies; however, rates are known to vary by season.

Objective: To assess exacerbation rates by season in ETHOS.

Methods: Patients with moderate-to-very severe COPD and ≥ 1 moderate/severe exacerbation in the prior year received BGF MDI 320/14.4/10 µg or 160/14.4/10 µg, glycopyrronium/formoterol (GFF) MDI 14.4/10 µg or budesonide/formoterol (BFF) MDI 320/10 µg twice-daily via a single Aerosphere inhaler. Annualised exacerbation rates were assessed using negative binomial regression.

Results: In the mITT population (n = 8509), 56.5% of patients had ≥ 2 exacerbations in the previous year. BGF MDI 320/14.4/10 µg and 160/14.4/10 µg reduced exacerbation rate vs. GFF MDI and BFF MDI ([Fig. 1]); rate ratios vs. GFF MDI for winter, spring, summer and fall were 0.83, 0.77, 0.71, 0.77 and 0.82, 0.82, 0.81, 0.66, respectively (all p < 0.02 [unadjusted]); and vs. BFF MDI were 0.88, 0.95, 0.80, 0.89 and 0.87, 1.01, 0.92, 0.77, respectively.

Abb. 1 Adjusted rate of moderate/severe COPD exacerbations per year for the efficacy estimand by season (modified intent to treat population).

Conclusions: In patients with moderate-to-very severe COPD and an exacerbation history, seasonal variation in exacerbation rate occurred in each treatment group. A reduction in exacerbation rate was generally observed across all seasons for BGF MDI (both dose levels) vs. LAMA/LABA and ICS/LABA.

Publication History

Article published online:
30 April 2021