对于中度慢性阻塞性肺疾病（COPD）患者，乌美溴铵/维兰特罗作为噻托溴铵的升级治疗：一项随机、平行组、为期12周的研究。

Umeclidinium/vilanterol as step-up therapy from tiotropium in patients with moderate COPD: a randomized, parallel-group, 12-week study.

作者信息

Kerwin Edward M, Kalberg Chris J, Galkin Dmitry V, Zhu Chang-Qing, Church Alison, Riley John H, Fahy William A

机构信息

Clinical Research Institute of Southern Oregon, Medford, OR.

Respiratory Department, GlaxoSmithKline, Research Triangle Park, NC, USA.

出版信息

Int J Chron Obstruct Pulmon Dis. 2017 Feb 24;12:745-755. doi: 10.2147/COPD.S119032. eCollection 2017.

INTRODUCTION

Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination. This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).

METHODS

In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks. Efficacy assessments included trough FEV at Day 85 (primary end point), 0-3 h serial FEV, rescue medication use, Transition Dyspnea Index (TDI), St George's Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT). Safety evaluations included adverse events (AEs).

RESULTS

Compared with TIO, UMEC/VI produced greater improvements in trough FEV (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; <0.001) and FEV after 5 min on Day 1 (50 mL [95% CI: 27-72]; <0.001). Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: -0.1 puffs/d [95% CI: -0.2-0.0]; ≤0.05). More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; ≤0.01). Improvements in SGRQ and CAT scores were similar between treatments. The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).

CONCLUSION

UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone.

引言

接受长效支气管扩张剂单药治疗仍有症状的慢性阻塞性肺疾病（COPD）患者，升级治疗至长效支气管扩张剂联合用药可能有益。本研究评估了乌美溴铵（UMEC）/维兰特罗（VI）在单独使用噻托溴铵（TIO）仍有症状的中度COPD患者中的疗效和安全性。

方法

在这项随机、双盲、双模拟、平行组研究（NCT01899742）中，筛选时接受TIO治疗≥3个月（第1秒用力呼气容积[FEV1]：预测值的50%-70%；改良医学研究委员会[mMRC]评分≥1）且完成4周TIO导入期的患者（N=494）被随机分为接受12周的UMEC/VI 62.5/25μg或TIO 18μg治疗。疗效评估包括第85天的FEV1谷值（主要终点）、0-3小时的系列FEV1、急救药物使用情况、过渡性呼吸困难指数（TDI）、圣乔治呼吸问卷（SGRQ）和慢性阻塞性肺疾病评估测试（CAT）。安全性评估包括不良事件（AE）。

结果

与TIO相比，UMEC/VI在第85天的FEV1谷值（最小二乘[LS]均值差异：88 mL[95%置信区间{CI}：45-131]；<0.001）和第1天5分钟后的FEV1（50 mL[95%CI：27-72]；<毛>0.001）方面改善更大。在12周内UMEC/VI组急救药物使用的减少幅度大于TIO组（LS均值变化：-0.1吸/天[95%CI：-0.2-0.0]；≤0.05）。与TIO组（49%）相比，更多接受UMEC/VI治疗的患者TDI评分实现了具有临床意义的改善（≥1个单位）（63%）；第84天的优势比=1.78[95%CI：1.21-2.64]；≤0.01）。两种治疗在SGRQ和CAT评分方面的改善相似。UMEC/VI组（30%）和TIO组（31%）的AE发生率相似。