Short-acting β₂-agonist use, exacerbation risk and triple therapy in COPD: post hoc analyses of ETHOS

Short-acting β₂-agonist (SABA) rescue therapy can relieve COPD symptoms. We assessed post-randomisation treatment effects on exacerbations and health-related quality of life in ETHOS by rescue SABA use.

In ETHOS (NCT02465567), symptomatic people with COPD and an exacerbation history were randomly assigned 1:1:1:1 to budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) (320/14.4/10 or 160/14.4/10 μg), glycopyrronium/formoterol fumarate dihydrate (GFF) (14.4/10 μg) or budesonide/formoterol fumarate dihydrate (BFF) (320/10 μg). Post hoc analyses assessed exacerbation rates by baseline and post-randomisation SABA use (>4 versus ≤4 inhalations·day^-1), St George's Respiratory Questionnaire change from baseline by post-randomisation SABA use (>4 versus ≤4 inhalations·day^-1), and post-randomisation SABA use surrounding (30 days before, day of onset, 30 days after) the first exacerbation.

Across treatments, higher moderate/severe exacerbation rates were observed for participants with higher (range: 1.62-2.51) versus lower (range: 1.14-1.51) SABA use at baseline or post-randomisation. Post-randomisation SABA use increased in the 30 days preceding, and decreased in the 30 days following, an exacerbation. Evidence of BGF benefit versus dual therapies in reducing moderate/severe exacerbation rates were seen regardless of SABA use level at baseline or post-randomisation, with greater BGF benefit observed versus GFF with higher SABA use (rate ratios (95% CI): high baseline SABA, 0.62 (0.53-0.72); high post-randomisation SABA, 0.64 (0.54-0.76)).

These results suggest increased SABA use is associated with an impending exacerbation. Further, BGF reduces exacerbation rates regardless of SABA use, with greater benefit in those with higher SABA use.