Bai Chunxue, Ichinose Masakazu, Lee Sang Haak, Lee Kwan Ho, Jöns Olaf, Bothner Ulrich, Zhao Yihua, Buhl Roland
Department of Pulmonary Medicine, Shanghai Respiratory Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Respiratory Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
Int J Chron Obstruct Pulmon Dis. 2017 Nov 20;12:3329-3339. doi: 10.2147/COPD.S137719. eCollection 2017.
While the efficacy and safety of combined tiotropium and olodaterol in patients with COPD was established in a large clinical trial program, it is important to assess whether clinical data can be applied to geographic patient groups, particularly for East Asian patients who may have a different phenotypic profile to the global trial population. This study aimed to compare the lung function and safety profiles of tiotropium/olodaterol and monocomponents in East Asian and global populations from the TONADO trials.
In the replicate, double-blind, parallel-group, active-controlled, randomized, 52-week, Phase III TONADO studies, patients received tiotropium/olodaterol, tiotropium, or olodaterol. We assessed the forced expiratory volume in 1 second (FEV) area under the curve from 0 to 3 hours (AUC) response and trough FEV response at 24 weeks for the approved doses, tiotropium/olodaterol 5/5 μg, tiotropium 5 μg, and olodaterol 5 μg. Treatment-emergent adverse events were recorded throughout treatment and ≤21 days after study medication.
In the East Asian population, 1,152 patients were randomized (5,163 overall). After 24 weeks, FEV AUC and trough FEV responses were greater (<0.0001) with tiotropium/olodaterol 5/5 μg in both populations versus tiotropium or olodaterol. The East Asian population showed slightly greater trough FEV treatment differences between tiotropium/olodaterol 5/5 μg and tiotropium compared to the overall population. Generally, no increase in adverse events was seen with tiotropium/olodaterol 5/5 μg compared to tiotropium and olodaterol in either population.
The efficacy and safety profile of tiotropium/olodaterol 5/5 μg has been demonstrated for both East Asian and global populations.
虽然在一项大型临床试验项目中已证实噻托溴铵与奥达特罗联合用药对慢性阻塞性肺疾病（COPD）患者的疗效和安全性，但评估临床数据是否可应用于不同地域的患者群体非常重要，尤其是对于可能与全球试验人群具有不同表型特征的东亚患者。本研究旨在比较东亚和全球人群中噻托溴铵/奥达特罗及其单一组分在肺功能和安全性方面的特征，这些数据来自TONADO试验。
在重复、双盲、平行组、活性对照、随机、为期52周的III期TONADO研究中，患者接受噻托溴铵/奥达特罗、噻托溴铵或奥达特罗治疗。我们评估了批准剂量（噻托溴铵/奥达特罗5/5μg、噻托溴铵5μg和奥达特罗5μg）在24周时0至3小时曲线下的1秒用力呼气容积（FEV）面积（AUC）反应以及谷值FEV反应。在整个治疗期间及研究药物停用后≤21天记录治疗中出现的不良事件。
在东亚人群中，有1152名患者被随机分组（全球共有5163名）。24周后，与噻托溴铵或奥达特罗相比，两个群体中使用5/5μg噻托溴铵/奥达特罗时的FEV AUC和谷值FEV反应均更高（<0.0001）。与总体人群相比，东亚人群中5/5μg噻托溴铵/奥达特罗与噻托溴铵之间的谷值FEV治疗差异略大。一般来说，在任何一个群体中，与噻托溴铵和奥达特罗相比，5/5μg噻托溴铵/奥达特罗并未导致不良事件增加。
已证实5/5μg噻托溴铵/奥达特罗对东亚和全球人群均具有疗效和安全性。
