Stolz Daiana, Hermansson Erik, Ouwens Mario, Singh Barinder, Sharma Akanksha, Jackson Dan, Darken Patrick, Marshall Jonathan, Bowen Karin, Müllerová Hana, Alcázar Navarrete Bernardino, Russell Richard, Han MeiLan K, Tansey-Dwyer Deniz
Clinic of Respiratory Medicine, Medical Center and Faculty of Medicine, University of Freiburg, Freiburg, Germany.
AstraZeneca, Gothenburg, Sweden.
Curr Med Res Opin. 2023 Oct;39(10):1395-1405. doi: 10.1080/03007995.2023.2247969. Epub 2023 Aug 29.
Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. While two approved fixed-dose inhaled corticosteroid/long-acting muscarinic antagonist (LAMA)/long-acting β-agonist (LABA) triple therapies reduce all-cause mortality (ACM) versus dual LAMA/LABA therapy in patients with COPD, head-to-head studies have not compared the effects of these therapies on ACM. We compared ACM in adults with moderate-to-very severe COPD receiving budesonide/glycopyrrolate/formoterol fumarate (BGF) in ETHOS versus fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in IMPACT using a matching-adjusted indirect comparison (MAIC).
A systematic literature review identified two studies (ETHOS [NCT02465567]; IMPACT [NCT02164513]) of ≥52 weeks reporting ACM as an efficacy endpoint in patients receiving triple therapy. As ETHOS and IMPACT lack a common comparator, an unanchored MAIC compared ACM between licensed doses of BGF (320/18/9.6 μg) from ETHOS and FF/UMEC/VI (100/62.5/25 μg) from IMPACT in patients with moderate-to-very severe COPD. Using on- and off-treatment data from the final retrieved datasets of the intention-to-treat populations, BGF data were adjusted according to aggregate FF/UMEC/VI data using 11 baseline covariates; a supplementary unadjusted indirect treatment comparison was also conducted. -values for these post-hoc analyses are not adjusted for Type I error.
ACM over 52 weeks was statistically significantly reduced by 39% for BGF versus FF/UMEC/VI in the MAIC (hazard ratio [HR] [95% CI]: 0.61 [0.38, 0.95], = 0.030) and unadjusted analysis (HR [95% CI]: 0.61 [0.41, 0.92], = 0.019).
In this MAIC, which adjusted for population heterogeneity between ETHOS and IMPACT, ACM was significantly reduced with BGF versus FF/UMEC/VI in patients with moderate-to-very severe COPD.
慢性阻塞性肺疾病（COPD）是全球主要的死亡原因之一。虽然两种已获批的吸入性糖皮质激素/长效毒蕈碱拮抗剂（LAMA）/长效β受体激动剂（LABA）固定剂量三联疗法相较于COPD患者的LAMA/LABA双联疗法可降低全因死亡率（ACM），但头对头研究尚未比较这些疗法对ACM的影响。我们采用匹配调整间接比较（MAIC）方法，比较了中度至重度COPD成人患者在ETHOS研究中接受布地奈德/格隆溴铵/富马酸福莫特罗（BGF）与在IMPACT研究中接受糠酸氟替卡松/乌美溴铵/维兰特罗（FF/UMEC/VI）后的ACM情况。
一项系统文献综述确定了两项≥52周的研究（ETHOS [NCT02465567]；IMPACT [NCT02164513]），这些研究将ACM作为接受三联疗法患者的疗效终点进行报告。由于ETHOS和IMPACT缺乏共同对照，一项非锚定MAIC比较了中度至重度COPD患者中ETHOS研究的BGF许可剂量（320/18/9.6μg）与IMPACT研究的FF/UMEC/VI许可剂量（100/62.5/25μg）之间的ACM情况。利用意向性治疗人群最终检索数据集的治疗期和非治疗期数据，根据汇总的FF/UMEC/VI数据，使用11个基线协变量对BGF数据进行调整；还进行了一项补充性的未调整间接治疗比较。这些事后分析的P值未针对I型错误进行调整。
在MAIC分析中，BGF组52周的ACM相较于FF/UMEC/VI组在统计学上显著降低了39%（风险比[HR][95%CI]：0.61[0.38, 0.95]，P = 0.030），未调整分析结果为（HR[95%CI]：0.61[0.41, 0.92]，P = 0.019）。
在这项针对ETHOS和IMPACT之间人群异质性进行调整的MAIC中，中度至重度COPD患者使用BGF相较于FF/UMEC/VI可显著降低ACM。
