Once daily glycopyrronium for the treatment of COPD: pooled analysis of the GLOW1 and GLOW2 studies

Background: Glycopyrronium is a once daily (o.d.) long-acting muscarinic antagonist that is approved for maintenance treatment of COPD. This post-hoc pooled analysis of two phase III studies, GLycopyrronium bromide in COPD airWays 1 and 2 (GLOW1 and GLOW2), evaluated the effects of glycopyrronium compared with placebo and tiotropium over 26-52 weeks in patients with moderate-to-severe COPD. Methods: Patients aged >= 40 years were randomised to 26 weeks' treatment with glycopyrronium 50 mu g o.d. or placebo (GLOW1) or 52 weeks' treatment with glycopyrronium 50 mg o.d., placebo, or open-label tiotropium 18 mg o.d. (GLOW2). The primary efficacy endpoint in both studies was trough forced expiratory volume in one second (FEV1) at Week 12. Other outcomes included additional spirometry endpoints, moderate or severe exacerbations, dyspnoea, health status, rescue medication use and safety. Serial spirometry over 24 hours was conducted in a subset of patients. Results: Of 1888 subjects randomised, 98.2% were analysed (glycopyrronium 1059, tiotropium 267, placebo 528). Least squares mean (LSM) trough FEV1 was significantly higher with glycopyrronium versus placebo at Week 12 (treatment difference +/- standard error [SE]: 103 +/- 11.2 mL; p<0.001), as well as at Day 1 and Weeks 26 and 52. More patients achieved >= 100 mL increase in trough FEV1 from baseline with glycopyrronium versus placebo at all assessments (p<0.001). Glycopyrronium significantly improved FEV1 immediately after the first dose on Day 1 versus placebo (90 mL at 5 minutes, 144 mL at 15 minutes; both p<0.001) and versus tiotropium (43 mL at 5 minutes, 65 mL at 15 minutes; both p<0.001). Glycopyrronium significantly improved other spirometry endpoints and provided clinically meaningful 24 hour bronchodilation versus placebo at most timepoints from Day 1 onwards (p<0.05). Time to first moderate or severe exacerbation was significantly prolonged with glycopyrronium versus placebo over 26 and 52 weeks (36% and 33%, respectively; both p<0.001). Glycopyrronium provided significantly greater relief of dyspnoea, improved health status and reduced rescue medication use versus placebo. Glycopyrronium was safe and well tolerated. Conclusions: Glycopyrronium 50 mg o.d. provided early bronchodilation after the first dose that was sustained for 24 hours, and reduced the risk of exacerbations compared with placebo, with efficacy at least equivalent to tiotropium.