LAUSR

Background: In the Phase III, 52-week ETHOS study (NCT02465567), budesonide/glycopyrronium/formoterol metered dose inhaler (BGF MDI) fixed-dose combination significantly reduced exacerbations vs dual therapies. However, use of inhaled corticosteroids (ICS) may also increase pneumonia risk. Objective: To quantify exacerbation benefits relative to pneumonia risk (expressed as numbers needed to treat [NNT] and numbers needed to harm [NNH], respectively) 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. Exacerbation and pneumonia rates were used to calculate NNT and NNH. Results: BGF MDI 320 µg reduced exacerbation rates vs GFF MDI (NNT=3 [95% CI 3, 5]) and vs BFF MDI (NNT=7 [95% CI 4, 18]), (mITT, N=8509). Pneumonia rates across treatments were 0.02–0.05 per patient year, and were lower for BGF MDI than BFF MDI; for BGF MDI 320 μg vs GFF MDI, NNH=58 (95% CI 29, 152; Table). Conclusions: In patients with moderate/very severe COPD, BGF MDI 320 µg reduced exacerbation risk vs both dual therapies. For the ICS component, the NNH (BGF MDI 320 μg vs GFF MDI) suggests a low pneumonia risk for BGF MDI relative to its benefits on exacerbations.