Department of Family and Community Medicine, University of Toronto , Ontario , Canada.
Curr Med Res Opin. 2014 Mar;30(3):493-508. doi: 10.1185/03007995.2013.858618. Epub 2013 Nov 19.
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.
Patients aged≥40 years were randomised to 26 weeks' treatment with glycopyrronium 50 μg o.d. or placebo (GLOW1) or 52 weeks' treatment with glycopyrronium 50 μg o.d., placebo, or open-label tiotropium 18 μg 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.
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.
Glycopyrronium 50 μg 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.
NCT01005901 and NCT00929110.
格隆溴铵是一种每日一次（o.d.）长效毒蕈碱拮抗剂，已被批准用于 COPD 的维持治疗。这项对两项 III 期研究（GLOW1 和 GLOW2）的事后汇总分析评估了格隆溴铵与安慰剂和噻托溴铵在 26-52 周内对中重度 COPD 患者的疗效。
年龄≥40 岁的患者随机接受 26 周格隆溴铵 50μg o.d.或安慰剂（GLOW1）或 52 周格隆溴铵 50μg o.d.、安慰剂或开放标签噻托溴铵 18μg o.d.治疗（GLOW2）。两项研究的主要疗效终点均为第 12 周的谷值用力呼气量（FEV1）。其他终点包括额外的肺量计终点、中度或重度加重、呼吸困难、健康状况、急救药物使用和安全性。对一部分患者进行了 24 小时连续肺量计检查。
在 1888 名随机患者中，98.2%（格隆溴铵 1059 例、噻托溴铵 267 例、安慰剂 528 例）进行了分析。与安慰剂相比，格隆溴铵在第 12 周时的谷值 FEV1 显著升高（治疗差异±标准误差[SE]：103±11.2mL；p<0.001），在第 1 天和第 26 周及第 52 周时也是如此。与安慰剂相比，更多的患者在所有评估中实现了谷值 FEV1 增加≥100mL（p<0.001）。与安慰剂相比，格隆溴铵在第 1 天第一次给药后即刻显著改善 FEV1（第 5 分钟时 90mL，第 15 分钟时 144mL；均 p<0.001），与噻托溴铵相比也显著改善（第 5 分钟时 43mL，第 15 分钟时 65mL；均 p<0.001）。格隆溴铵在大多数时间点（从第 1 天开始）均显著改善其他肺量计终点，并提供了有临床意义的 24 小时支气管扩张作用，优于安慰剂（p<0.05）。与安慰剂相比，格隆溴铵在 26 周和 52 周时首次发生中度或重度加重的时间显著延长（分别为 36%和 33%；均 p<0.001）。与安慰剂相比，格隆溴铵显著改善呼吸困难、健康状况并减少急救药物使用。格隆溴铵安全且耐受良好。
格隆溴铵 50μg o.d.在第一次给药后立即产生支气管扩张作用，持续 24 小时，与安慰剂相比，降低了加重的风险，其疗效至少与噻托溴铵相当。
NCT01005901 和 NCT00929110。
