Data from: Once-daily long-acting beta-agonists for chronic obstructive pulmonary disease: an indirect comparison of olodaterol and indacaterol

Purpose: 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. Methods: 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. Results: 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. Conclusion: 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.

研究目的：目前尚无头对头临床试验对比每日一次长效β2受体激动剂（long-acting beta2-agonists）奥达特罗（olodaterol）与茚达特罗（indacaterol）治疗慢性阻塞性肺疾病（chronic obstructive pulmonary disease, COPD）的疗效，本研究通过系统评价并综合现有临床证据开展间接治疗比较。
研究方法：针对慢阻肺患者开展随机对照临床试验的系统综述，以评估奥达特罗与茚达特罗的疗效与安全性。采用网络Meta分析（network meta-analysis）及校正间接比较法（adjusted indirect comparison）评估治疗疗效，研究结局包括1秒用力呼气容积谷值（trough forced expiratory volume in 1 second, FEV1）、过渡性呼吸困难指数（Transition Dyspnea Index, TDI）、圣乔治呼吸问卷（St George’s Respiratory Questionnaire, SGRQ）总评分及应答率、急救药物使用情况、急性加重患者比例。
研究结果：共纳入18项试验用于Meta分析（奥达特罗组8项，茚达特罗组10项）。奥达特罗相关试验纳入了所有严重程度的慢阻肺患者，而茚达特罗相关试验则排除了极重度慢阻肺患者。多数奥达特罗试验允许合并使用维持性支气管扩张剂，但茚达特罗试验未作此要求。对设计相似的试验/数据进行基线后谷值FEV1（单位：升）变化分析时，得到如下均数差（95%置信区间，95%CI）：排除合并支气管扩张剂的试验中，茚达特罗75μg对比奥达特罗5μg的均数差为-0.005（95%CI：-0.077~0.067），茚达特罗150μg对比奥达特罗5μg的均数差为0.020（95%CI：-0.036~0.077）；合并使用噻托溴铵（tiotropium）的试验中，茚达特罗150μg对比奥达特罗5μg的均数差为0.000（95%CI：-0.043~0.042）。对完整研究网络进行敏感性分析时，谷值FEV1基线后变化的结果倾向于茚达特罗，但该数据集存在试验设计异质性问题。针对其他研究终点的完整网络分析未发现具有统计学意义的差异。
研究结论：在相似的试验条件下对比，奥达特罗与茚达特罗在慢阻肺患者中的疗效相当。本研究强调，在评估慢阻肺治疗效果时，需充分考虑患者合并使用的慢阻肺治疗药物的影响。