Abstract：
UNASSIGNED: 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 β2-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).
UNASSIGNED: 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. P-values for these post-hoc analyses are not adjusted for Type I error.
UNASSIGNED: 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], p = 0.030) and unadjusted analysis (HR [95% CI]: 0.61 [0.41, 0.92], p = 0.019).
UNASSIGNED: 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.
Chronic obstructive pulmonary disease (known as COPD) is a leading cause of death worldwide, being responsible for over 3 million deaths in 2019. People living with COPD are more likely to die. Importantly, a sudden worsening of COPD symptoms (known as an exacerbation) is associated with a higher chance of death from heart-related and breathing-related problems. Therefore, reducing risk of death is an important treatment goal for COPD. Of the three medications approved for treating COPD that combine three drugs in a single-inhaler device, there are two—referred to generically as budesonide/glycopyrrolate/formoterol fumarate (BGF) and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)—that can reduce the risk of death in people living with COPD compared with treatments that combine two drugs. However, no studies have directly compared the risk of death in people living with COPD treated with these medicines. We compared the risk of death in people living with moderate-to-very severe COPD who received either BGF during a clinical trial called ETHOS or FF/UMEC/VI during a clinical trial called IMPACT. To make this comparison, we used a method called “matching-adjusted indirect comparison”, which used specific features (such as sex, breathing difficulty, and whether they were current smokers) to match patients from the two studies to ensure similar groups were examined. Our analysis showed a 39% decrease in the chance of death in patients who received BGF compared with patients who received FF/UMEC/VI. This finding may be important for doctors to improve patient health and reduce the risk of death in people living with COPD.
UNASSIGNED: 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. P-values for these post-hoc analyses are not adjusted for Type I error.
UNASSIGNED: 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], p = 0.030) and unadjusted analysis (HR [95% CI]: 0.61 [0.41, 0.92], p = 0.019).
UNASSIGNED: 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.
Chronic obstructive pulmonary disease (known as COPD) is a leading cause of death worldwide, being responsible for over 3 million deaths in 2019. People living with COPD are more likely to die. Importantly, a sudden worsening of COPD symptoms (known as an exacerbation) is associated with a higher chance of death from heart-related and breathing-related problems. Therefore, reducing risk of death is an important treatment goal for COPD. Of the three medications approved for treating COPD that combine three drugs in a single-inhaler device, there are two—referred to generically as budesonide/glycopyrrolate/formoterol fumarate (BGF) and fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI)—that can reduce the risk of death in people living with COPD compared with treatments that combine two drugs. However, no studies have directly compared the risk of death in people living with COPD treated with these medicines. We compared the risk of death in people living with moderate-to-very severe COPD who received either BGF during a clinical trial called ETHOS or FF/UMEC/VI during a clinical trial called IMPACT. To make this comparison, we used a method called “matching-adjusted indirect comparison”, which used specific features (such as sex, breathing difficulty, and whether they were current smokers) to match patients from the two studies to ensure similar groups were examined. Our analysis showed a 39% decrease in the chance of death in patients who received BGF compared with patients who received FF/UMEC/VI. This finding may be important for doctors to improve patient health and reduce the risk of death in people living with COPD.
摘要：
■慢性阻塞性肺疾病(COPD)是全球范围内的主要死亡原因。虽然两种批准的固定剂量吸入性皮质类固醇/长效毒蕈碱拮抗剂（LAMA）/长效β2激动剂（LABA）三联疗法与LAMA/LABA双重疗法相比，可降低COPD患者的全因死亡率（ACM），头对头研究没有比较这些疗法对ACM的影响.我们使用匹配调整的间接比较（MAIC）比较了在ETHOS中接受布地奈德/格隆溴铵/富马酸福莫特罗（BGF）的中度至非常重度COPD成年人的ACM与在IMPACT中接受糠酸氟替卡松/umecidinum/vilanterol（FF/UMEC/VI）的ACM。
■一项系统文献综述确定了两项≥52周的研究(ETHOS[NCT02465567];IMPACT[NCT02164513])报告ACM为接受三联疗法的患者的疗效终点。由于ETHOS和IMPACT缺乏共同的比较器，一项未锚定的MAIC比较了来自ETHOS的许可剂量BGF(320/18/9.6μg)和来自IMPACT的FF/UMEC/VI(100/62.5/25μg)在中度至非常重度COPD患者中的ACM.使用来自最终检索的意向治疗人群数据集的治疗前和治疗外数据，使用11个基线协变量，根据总FF/UMEC/VI数据调整BGF数据；还进行了补充的未调整的间接治疗比较。这些事后分析的P值没有针对I型误差进行调整。
■在MAIC中，BGF与FF/UMEC/VI在52周内的ACM在统计学上显着降低了39％（风险比[HR][95％CI]：0.61[0.38，0.95]，P=0.030）和未调整分析（HR[95%CI]：0.61[0.41，0.92]，P=0.019)。
■在此MAIC中，调整了ETHOS和IMPACT之间的人口异质性，在中度至非常重度COPD患者中，BGF与FF/UMEC/VI相比，ACM显着降低。
慢性阻塞性肺疾病（被称为COPD）是全球主要的死亡原因，在2019年造成超过300万人死亡。患有COPD的人更容易死亡。重要的是,COPD症状突然恶化(称为加重)与心脏相关和呼吸相关问题的死亡机率较高相关.因此,降低死亡风险是COPD治疗的重要目标.在批准用于治疗COPD的三种药物中，将三种药物结合在单吸入器装置中，有两种-通常被称为布地奈德/格隆溴铵/富马酸福莫特罗(BGF)和糠酸氟替卡松/戊地铵/维兰特罗(FF/UMEC/VI)-与联合使用两种药物的治疗相比,可以降低COPD患者的死亡风险.然而,没有研究直接比较使用这些药物治疗的COPD患者的死亡风险.我们比较了在一项名为ETHOS的临床试验中接受BGF或在一项名为IMPACT的临床试验中接受FF/UMEC/VI的中度至非常重度COPD患者的死亡风险。为了做这个比较，我们使用了一种叫做“匹配调整间接比较”的方法它使用了特定的特征(比如性别，呼吸困难,以及他们是否是当前的吸烟者），以匹配两项研究的患者，以确保对相似的组进行检查。我们的分析显示，与接受FF/UMEC/VI的患者相比，接受BGF的患者死亡机会减少了39％。这一发现对于医生改善患者健康和降低COPD患者死亡风险可能很重要。
■一项系统文献综述确定了两项≥52周的研究(ETHOS[NCT02465567];IMPACT[NCT02164513])报告ACM为接受三联疗法的患者的疗效终点。由于ETHOS和IMPACT缺乏共同的比较器，一项未锚定的MAIC比较了来自ETHOS的许可剂量BGF(320/18/9.6μg)和来自IMPACT的FF/UMEC/VI(100/62.5/25μg)在中度至非常重度COPD患者中的ACM.使用来自最终检索的意向治疗人群数据集的治疗前和治疗外数据，使用11个基线协变量，根据总FF/UMEC/VI数据调整BGF数据；还进行了补充的未调整的间接治疗比较。这些事后分析的P值没有针对I型误差进行调整。
■在MAIC中，BGF与FF/UMEC/VI在52周内的ACM在统计学上显着降低了39％（风险比[HR][95％CI]：0.61[0.38，0.95]，P=0.030）和未调整分析（HR[95%CI]：0.61[0.41，0.92]，P=0.019)。
■在此MAIC中，调整了ETHOS和IMPACT之间的人口异质性，在中度至非常重度COPD患者中，BGF与FF/UMEC/VI相比，ACM显着降低。
慢性阻塞性肺疾病（被称为COPD）是全球主要的死亡原因，在2019年造成超过300万人死亡。患有COPD的人更容易死亡。重要的是,COPD症状突然恶化(称为加重)与心脏相关和呼吸相关问题的死亡机率较高相关.因此,降低死亡风险是COPD治疗的重要目标.在批准用于治疗COPD的三种药物中，将三种药物结合在单吸入器装置中，有两种-通常被称为布地奈德/格隆溴铵/富马酸福莫特罗(BGF)和糠酸氟替卡松/戊地铵/维兰特罗(FF/UMEC/VI)-与联合使用两种药物的治疗相比,可以降低COPD患者的死亡风险.然而,没有研究直接比较使用这些药物治疗的COPD患者的死亡风险.我们比较了在一项名为ETHOS的临床试验中接受BGF或在一项名为IMPACT的临床试验中接受FF/UMEC/VI的中度至非常重度COPD患者的死亡风险。为了做这个比较，我们使用了一种叫做“匹配调整间接比较”的方法它使用了特定的特征(比如性别，呼吸困难,以及他们是否是当前的吸烟者），以匹配两项研究的患者，以确保对相似的组进行检查。我们的分析显示，与接受FF/UMEC/VI的患者相比，接受BGF的患者死亡机会减少了39％。这一发现对于医生改善患者健康和降低COPD患者死亡风险可能很重要。
