National Heart and Lung Institute, Imperial College London, London, UK.
Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany.
Adv Ther. 2021 May;38(5):2249-2270. doi: 10.1007/s12325-021-01646-5. Epub 2021 Mar 15.
In patients with chronic obstructive pulmonary disease (COPD), treatment with long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) combination therapy significantly improves lung function versus LABA/inhaled corticosteroid (ICS). To investigate whether LAMA/LABA could provide better clinical outcomes than LABA/ICS, this non-interventional database study assessed the risk of COPD exacerbations, pneumonia, and escalation to triple therapy in patients with COPD initiating maintenance therapy with tiotropium/olodaterol versus any LABA/ICS combination.
Administrative healthcare claims and laboratory results data from the US HealthCore Integrated Research Database were evaluated for patients with COPD initiating tiotropium/olodaterol versus LABA/ICS treatment (January 2013-March 2019). Patients were aged at least 40 years with a diagnosis of COPD (but not asthma) at cohort entry. A Cox proportional hazard regression model was used (as-treated analysis) to assess risk of COPD exacerbation, community-acquired pneumonia, and escalation to triple therapy, both individually and as a combined risk of any one of these events. Potential imbalance of confounding factors between cohorts was handled using fine stratification, reweighting, and trimming by exposure propensity score (high-dimensional); subgroup analyses were conducted on the basis of blood eosinophil levels and exacerbation history.
The total population consisted of 61,985 patients (tiotropium/olodaterol n = 2684; LABA/ICS n = 59,301); after reweighting, the total was 42,953 patients (tiotropium/olodaterol n = 2600; LABA/ICS n = 40,353; mean age 65 years; female 54.5%). Patients treated with tiotropium/olodaterol versus LABA/ICS experienced a reduction in the risk of COPD exacerbations (adjusted hazard ratio 0.76 [95% confidence interval 0.68, 0.85]), pneumonia (0.74 [0.57, 0.97]), escalation to triple therapy (0.22 [0.19, 0.26]), and any one of these events (0.45 [0.41, 0.49]); the combined risk was similar irrespective of baseline eosinophils and exacerbation history.
In patients with COPD, tiotropium/olodaterol was associated with a lower risk of COPD exacerbations, pneumonia, and escalation to triple therapy versus LABA/ICS, both individually and in combination; the combined risk was reduced irrespective of baseline eosinophils or exacerbation history.
ClinicalTrials.gov identifier, NCT04138758 (registered 23 October 2019).
在慢性阻塞性肺疾病（COPD）患者中，长效抗毒蕈碱药（LAMA）/长效β-激动剂（LABA）联合治疗与 LABA/吸入皮质类固醇（ICS）相比，显著改善了肺功能。为了研究 LAMA/LABA 是否能提供比 LABA/ICS 更好的临床结果，本项非干预性数据库研究评估了 COPD 患者起始噻托溴铵/奥达特罗维持治疗与任何 LABA/ICS 联合治疗相比，发生 COPD 加重、肺炎和升级为三联治疗的风险。
使用美国 HealthCore 综合研究数据库的行政医疗保健索赔和实验室结果数据评估了起始噻托溴铵/奥达特罗与 LABA/ICS 治疗的 COPD 患者（2013 年 1 月至 2019 年 3 月）。患者年龄至少 40 岁，在入组时患有 COPD（但无哮喘）。采用 Cox 比例风险回归模型（按治疗分析）评估 COPD 加重、社区获得性肺炎和升级为三联治疗的风险，以及这些事件中任何一种的联合风险。使用精细分层、重新加权和通过暴露倾向评分（高维）修剪来处理队列之间潜在的混杂因素失衡。根据血嗜酸性粒细胞水平和加重史进行亚组分析。
总人群由 61985 例患者组成（噻托溴铵/奥达特罗 n=2684；LABA/ICS n=59301）；经重新加权后，总人数为 42953 例（噻托溴铵/奥达特罗 n=2600；LABA/ICS n=40353；平均年龄 65 岁；女性占 54.5%）。与 LABA/ICS 相比，噻托溴铵/奥达特罗治疗的患者 COPD 加重（调整后的危险比 0.76[95%置信区间 0.68，0.85]）、肺炎（0.74[0.57，0.97]）、升级为三联治疗（0.22[0.19，0.26]）和任何一种这些事件（0.45[0.41，0.49]）的风险降低；无论基线嗜酸性粒细胞和加重史如何，联合风险相似。
在 COPD 患者中，与 LABA/ICS 相比，噻托溴铵/奥达特罗治疗与 COPD 加重、肺炎和升级为三联治疗的风险降低，无论是单独使用还是联合使用；无论基线嗜酸性粒细胞或加重史如何，联合风险都降低了。
ClinicalTrials.gov 标识符，NCT04138758（2019 年 10 月 23 日注册）。
