[The efficacy and safety of tiotropium/olodaterol fixed-dose combination in Chinese patients with chronic obstructive pulmonary disease: a pooled subgroup analysis of TONADO 1+2].

Objective: To compare the efficacy and safety profiles of tiotropium/olodaterol with the mono-components in Chinese and total study population from TONADO trial. Methods: In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase Ⅲ TONADO studies (TONADO 1+2), patients received tiotropium/olodaterol, tiotropium, or olodaterol via the Respimat(®) Inhaler (Boehringer Ingelheim, Germany). Primary end points were forced expiratory volume in 1 second (FEV(1)) area under the curve from 0 to 3 hours (AUC(0-3h)) response and trough FEV(1) response, and St George's respiratory questionnaire (SGRQ) total score at 24 weeks. Adverse events were also collected. This subgroup analysis only focused on the efficacy and safety of the drug at the approved dose in China. Results: 548 Chinese patients were randomized, aged 41 to 82 years [mean age, (63±8) years] and most were male (526, 96%), 111 received tiotropium/olodaterol 5/5 μg, and 127 received tiotropium 5 μg and 95 received olodaterol 5 μg. The baseline characteristics of these groups were similar. After 24 weeks, treatment with tiotropium/olodaterol 5/5 μg, tiotropium 5 μg and olodaterol 5 μg resulted in an adjusted mean FEV(1) AUC(0-3h) response of 0.240, 0.157 and 0.079 L, and trough FEV(1) response of 0.117, 0.068 and-0.001 L, respectively. Tiotropium/olodaterol 5/5 μg significantly improved SGRQ scores in Chinese patients compared with olodaterol 5 μg (32.729 and 37.202, respectively). Generally, the safety profile of tiotropium/olodaterol was comparable with mono-components in 52 weeks. Conclusion: Compared with tiotropium or olodaterol, tiotropium/olodaterol in Chinese patients provided significant improvement in lung function and quality of life, and the safety profiles were similar.目的： 分析两项慢性阻塞性肺疾病（慢阻肺）Ⅲ期临床研究（TONADO 1+2）的中国患者亚组数据，比较双支气管舒张剂（噻托溴铵/奥达特罗）与单药治疗在我国慢阻肺患者中的有效性与安全性。 方法： TONADO 1+2为重复的52周、随机、双盲、平行分组和阳性对照研究，患者通过软雾吸入器（商品名为能倍乐(®)）接受噻托溴铵/奥达特罗、噻托溴铵或奥达特罗治疗。TONADO 1+2在全球范围招募了5 163例慢阻肺患者，其中667例来自我国，548例通过IXRS系统随机分配接受治疗，其中男526例，女22例，年龄41~82岁，平均（63±8）岁；495例（495/548，90.3%）完成治疗，53例（53/495，9.7%）提前停药，最常见的提前停药原因是发生不良事件（31/548，5.7%）。本文仅分析接受我国批准使用的药物剂量治疗的患者，最终纳入333例，其中男320例，女3例，年龄41~82岁。111例使用噻托溴铵/奥达特罗5/5 μg（双药组），其中男107例，女4例，年龄41~81岁，平均（63±8）岁；127例使用噻托溴铵5 μg（噻托溴铵组），其中男124例，女3例，年龄42~81岁，平均（64±8）岁；95例使用奥达特罗5 μg（奥达特罗组），其中男89例，女6例，年龄44~82岁，平均（62±8）岁，各组基线资料差异无统计学意义（P>0.05）。主要研究终点包括：治疗24周后评估给药后0~3 h的FEV(1)曲线下面积（FEV(1) AUC(0-3h)）、FEV(1)最低值和圣乔治呼吸问卷（SGRQ）总分。同时收集研究期间的不良事件。 结果： 治疗24周后，双药组、噻托溴铵组和奥达特罗组FEV(1) AUC(0-3h)较基线的变化分别为0.240、0.157和0.079 L，FEV(1)最低值较基线的变化分别为0.117、0.068和-0.001 L。双药组SGRQ为32.7分，较奥达特罗组（37.2分）明显改善。在52周的治疗期内，双支气管舒张剂的安全性与单药治疗相当。 结论： 在中国亚组患者中，噻托溴铵/奥达特罗较单药可进一步改善中国亚组患者的肺功能和生活质量，药物安全性与单药相当。.