噻托溴铵/奥达特罗与噻托溴铵单药治疗早期 COPD 患者的临床重要恶化的比较：TONADO 试验的事后分析。
Tiotropium/Olodaterol Delays Clinically Important Deterioration Compared with Tiotropium Monotherapy in Patients with Early COPD: a Post Hoc Analysis of the TONADO Trials.
机构信息
LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research (DZL), Grosshansdorf, Germany.
Christian Albrechts University Kiel, Airway Research Center North, German Center for Lung Research (DZL), Kiel, Germany.
出版信息
Adv Ther. 2021 Jan;38(1):579-593. doi: 10.1007/s12325-020-01528-2. Epub 2020 Nov 11.
INTRODUCTION
Since chronic obstructive pulmonary disease (COPD) is a heterogeneous condition, a composite endpoint of clinically important deterioration (CID) may provide a more holistic assessment of treatment efficacy. We compared long-acting muscarinic antagonist/long-acting β-agonist combination therapy with tiotropium/olodaterol versus tiotropium alone using a composite endpoint for CID. CID was evaluated overall and in patients with low exacerbation history (at most one moderate exacerbation in the past year [not leading to hospitalisation]), Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2 patients and maintenance-naïve patients with COPD. We assessed whether early treatment optimisation is more effective with tiotropium/olodaterol versus tiotropium in delaying and reducing the risk of CID.
METHODS
Data were analysed from 2055 patients treated with either tiotropium/olodaterol 5/5 μg or tiotropium 5 μg (delivered via Respimat) in two replicate, 52-week, parallel-group, double-blind studies (TONADO 1/2). CID was defined as a decline of at least 0.1 L from baseline in trough forced expiratory volume in 1 s, increase from baseline of at least 4 units in St. George's Respiratory Questionnaire score, or moderate/severe exacerbation. Time to first occurrence of one of these events was recorded as time to first CID.
RESULTS
Overall, treatment with tiotropium/olodaterol significantly increased the time to, and reduced the risk of, CID versus tiotropium (median time to CID 226 versus 169 days; hazard ratio [HR] 0.76 [95% confidence interval 0.68, 0.85]; P < 0.0001). Significant reductions were also observed in patients with low exacerbation history (241 versus 170; HR 0.73 [0.64, 0.83]; P < 0.0001), GOLD 2 patients (241 versus 169; 0.72 [0.61, 0.84]; P < 0.0001) and maintenance-naïve patients (233 versus 171; 0.75 [0.62, 0.91]; P = 0.0030).
CONCLUSION
In patients with COPD, including patients with low exacerbation history, GOLD 2 patients and maintenance-naïve patients, tiotropium/olodaterol reduced the risk of CID versus tiotropium. These results demonstrate the advantages of treatment optimisation with tiotropium/olodaterol over tiotropium monotherapy.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: TONADO 1 and 2 (NCT01431274 and NCT01431287, registered 8 September 2011).
简介
由于慢性阻塞性肺疾病（COPD）是一种异质性疾病，临床上重要的恶化（CID）综合终点可能提供更全面的治疗效果评估。我们比较了长效毒蕈碱拮抗剂/长效β-激动剂联合治疗与噻托溴铵/奥达特罗在CID 综合终点方面的疗效。总体上和在过去一年中（无导致住院的中重度加重）仅有一次中重度加重史的患者、GOLD 2 患者和 COPD 初始维持治疗患者中评估了 CID。我们评估了与噻托溴铵相比，早期治疗优化对噻托溴铵/奥达特罗延迟和降低 CID 风险是否更有效。
方法
对接受噻托溴铵/奥达特罗 5/5μg 或噻托溴铵 5μg（通过 Respimat 给药）治疗的 2055 例患者的双盲、平行分组、为期 52 周的两项重复 TONADO 1/2 研究中的数据进行了分析。CID 定义为： trough 用力呼气量 1 秒率从基线下降至少 0.1 L，圣乔治呼吸问卷评分比基线至少增加 4 个单位，或中度/重度加重。记录首次发生这些事件之一的时间作为首次 CID 的时间。
结果
总体而言，与噻托溴铵相比，噻托溴铵/奥达特罗显著延迟了 CID 的发生，并降低了 CID 的风险（CID 的中位时间为 226 天 vs. 169 天；风险比 [HR] 0.76 [95%置信区间 0.68，0.85]；P<0.0001）。在过去一年中仅有一次中重度加重史的患者（241 天 vs. 170 天；HR 0.73 [0.64，0.83]；P<0.0001）、GOLD 2 患者（241 天 vs. 169 天；0.72 [0.61，0.84]；P<0.0001）和初始维持治疗患者（233 天 vs. 171 天；0.75 [0.62，0.91]；P=0.0030）中，也观察到了显著的降低。
结论
在 COPD 患者中，包括有低加重史、GOLD 2 患者和初始维持治疗患者，噻托溴铵/奥达特罗降低了 CID 的风险。这些结果表明，与噻托溴铵单药治疗相比，噻托溴铵/奥达特罗治疗优化具有优势。
试验注册
ClinicalTrials.gov 标识符：TONADO 1 和 2（NCT01431274 和 NCT01431287，2011 年 9 月 8 日注册）。
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