Roskell Neil S, Anzueto Antonio, Hamilton Alan, Disse Bernd, Becker Karin
Statistics, Bresmed Health Solutions Ltd, Sheffield, UK.
School of Medicine, University of Texas Health Science Center, San Antonio, TX, USA.
Int J Chron Obstruct Pulmon Dis. 2014 Jul 31;9:813-24. doi: 10.2147/COPD.S59673. eCollection 2014.
In the absence of head-to-head clinical trials comparing the once-daily, long-acting beta2-agonists olodaterol and indacaterol for the treatment of chronic obstructive pulmonary disease (COPD), an indirect treatment comparison by systematic review and synthesis of the available clinical evidence was conducted.
A systematic literature review of randomized, controlled clinical trials in patients with COPD was performed to evaluate the efficacy and safety of olodaterol and indacaterol. Network meta-analysis and adjusted indirect comparison methods were employed to evaluate treatment efficacy, using outcomes based on trough forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, St George's Respiratory Questionnaire total score and response, rescue medication use, and proportion of patients with exacerbations.
Eighteen trials were identified for meta-analysis (eight, olodaterol; ten, indacaterol). Olodaterol trials included patients of all severities, whilst indacaterol trials excluded patients with very severe COPD. Concomitant maintenance bronchodilator use was allowed in most olodaterol trials, but not in indacaterol trials. When similarly designed trials/data were analyzed for change from baseline in trough FEV1 (liters), the following mean differences (95% confidence interval) were observed: trials excluding concomitant bronchodilator: indacaterol 75 mcg versus olodaterol 5 mcg, -0.005 (-0.077 to 0.067), and indacaterol 150 mcg versus olodaterol 5 mcg, 0.020 (-0.036 to 0.077); trials with concomitant tiotropium: indacaterol 150 mcg versus olodaterol 5 mcg, 0.000 (-0.043 to 0.042). In sensitivity analyses of the full network, results for change from baseline in trough FEV1 favored indacaterol, but this dataset suffered from trial design heterogeneity. For the other endpoints investigated, no statistically significant differences were found when analyzed in the full network.
When compared under similar trial conditions, olodaterol and indacaterol have similar efficacy in patients with COPD. This research highlights the importance of considering the concomitant COPD medication when evaluating treatment effects in COPD.
在缺乏头对头临床试验比较每日一次长效β2受体激动剂奥达特罗和茚达特罗治疗慢性阻塞性肺疾病(COPD)的情况下,通过系统评价和综合现有临床证据进行间接治疗比较。
对COPD患者的随机对照临床试验进行系统文献回顾,以评估奥达特罗和茚达特罗的疗效和安全性。采用网络荟萃分析和调整后的间接比较方法评估治疗效果,使用基于1秒用力呼气容积(FEV1)谷值、过渡性呼吸困难指数、圣乔治呼吸问卷总分及应答、急救药物使用和急性加重患者比例的结局指标。
共纳入18项试验进行荟萃分析(8项奥达特罗试验;10项茚达特罗试验)。奥达特罗试验纳入了所有严重程度的患者,而茚达特罗试验排除了极重度COPD患者。大多数奥达特罗试验允许同时使用维持性支气管扩张剂,但茚达特罗试验不允许。当对设计相似的试验/数据进行分析,以观察FEV1谷值相对于基线的变化(升)时,观察到以下平均差异(95%置信区间):排除同时使用支气管扩张剂的试验:茚达特罗75微克对比奥达特罗5微克,-0.005(-0.077至0.067),以及茚达特罗150微克对比奥达特罗5微克,0.020(-0.036至0.077);同时使用噻托溴铵的试验:茚达特罗150微克对比奥达特罗5微克,0.000(-0.043至0.042)。在全网络的敏感性分析中,FEV1谷值相对于基线的变化结果有利于茚达特罗,但该数据集存在试验设计异质性。对于其他研究的终点指标,在全网络分析时未发现统计学上的显著差异。
在相似的试验条件下进行比较时,奥达特罗和茚达特罗在COPD患者中具有相似的疗效。本研究强调了在评估COPD治疗效果时考虑同时使用的COPD药物的重要性。