评估初治慢性阻塞性肺疾病（COPD）患者接受阿地溴铵/维兰特罗和噻托溴铵治疗后的短期病情恶化情况：三项随机试验的汇总分析
Assessing Short-term Deterioration in Maintenance-naïve Patients with COPD Receiving Umeclidinium/Vilanterol and Tiotropium: A Pooled Analysis of Three Randomized Trials.
作者信息
Maleki-Yazdi M Reza, Singh Dave, Anzueto Antonio, Tombs Lee, Fahy William A, Naya Ian
机构信息
Division of Respiratory Medicine, Women's College Hospital, University of Toronto, Toronto, ON, Canada.
Medicines Evaluation Unit, University of Manchester, University Hospital of South Manchester Foundation Trust, Manchester, UK.
出版信息
Adv Ther. 2017 Jan;33(12):2188-2199. doi: 10.1007/s12325-016-0430-6. Epub 2016 Oct 28.
INTRODUCTION
Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy. The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.
METHODS
This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747). Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis. The primary endpoint was trough forced expiratory volume in 1 s (FEV). St George's Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.
RESULTS
UMEC/VI improved trough FEV versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001]. Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO. UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001]. Adverse events were similar across both populations and treatments.
CONCLUSIONS
Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.
CLINICAL TRIAL REGISTRATION
GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).
FUNDING
This study was funded by GSK.
引言
双重支气管扩张剂疗法在慢性阻塞性肺疾病（COPD）患者中作为二线治疗方案，与单一疗法相比，其在肺功能和健康状况方面具有优势。本研究的目的是确定与单一疗法相比，早期启用双重支气管扩张剂是否能降低COPD病情恶化的风险。
方法
这项事后汇总分析研究了在三项为期6个月的活性对照研究（n = 1747）中，与18微克/天的噻托溴铵（TIO）相比，62.5/25微克/天的乌美溴铵/维兰特罗（UMEC/VI）在初治（MN）亚组患者相对于意向性治疗（ITT）人群中的疗效和安全性。其他治疗组（UMEC/VI 125/25、VI 25和UMEC 125）共有850名患者，但未纳入本分析。主要终点是第1秒用力呼气容积（FEV）谷值。还评估了圣乔治呼吸问卷（SGRQ）评分、急救药物使用情况以及短期临床重要恶化的新复合终点（CID；FEV谷值下降≥100毫升、SGRQ评分增加≥4分或COPD急性加重）。
结果
在第169天时，UMEC/VI相对于TIO改善了FEV谷值[最小二乘均值（95%置信区间）：MN：146毫升（102 - 189）；ITT：95毫升（71 - 118）；P均<0.001]。UMEC/VI和TIO在两个人群中均改善了SGRQ和急救药物使用情况，与TIO相比，UMEC/VI在急救药物使用改善方面更显著。与TIO相比，UMEC/VI降低了短期临床重要恶化的风险[风险比；95%置信区间：MN：0.66（0.51 - 0.85）；ITT：0.62（0.54 - 0.71），P均≤0.001]。两个人群和治疗组的不良事件相似。
结论
对于有症状COPD患者，与单一疗法相比，早期使用双重支气管扩张剂疗法对肺功能具有更好的疗效，且可能降低短期病情恶化的风险。
临床试验注册
GSK分析202066（NCT01316900/DB2113360，NCT01316913/DB2113374，NCT01777334/ZEP117115）。
资助
本研究由葛兰素史克公司资助。
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