布地奈德/格隆溴铵/富马酸福莫特罗二水合物三联疗法与双重疗法治疗慢性阻塞性肺疾病合并哮喘表型特征患者的比较：KRONOS和ETHOS的汇总事后分析
Triple Therapy with Budesonide/Glycopyrronium/Formoterol Fumarate Dihydrate versus Dual Therapies for Patients with COPD and Phenotypic Features of Asthma: A Pooled Post Hoc Analysis of KRONOS and ETHOS.
作者信息
Muro Shigeo, Seki Munehiro, Hurst John R, Petullo David, Marshall Jonathan, Bowen Karin, Darken Patrick F, Duncan Elizabeth A, Megally Ayman, Patel Mehul
机构信息
Department of Respiratory Medicine, Nara Medical University, Nara, Japan.
AstraZeneca K.K., Osaka, Japan.
出版信息
Int J Chron Obstruct Pulmon Dis. 2024 Dec 12;19:2729-2737. doi: 10.2147/COPD.S478349. eCollection 2024.
BACKGROUND
We evaluated the inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β-agonist (ICS/LAMA/LABA) triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual LAMA/LABA and ICS/LABA therapies in patients with chronic obstructive pulmonary disease (COPD) and phenotypic features of asthma (bronchodilator reversibility and elevated blood eosinophils), but no asthma diagnosis, for whom treatment guidelines are limited.
PATIENTS AND METHODS
KRONOS (NCT02497001) and ETHOS (NCT02465567) enrolled patients with moderate-to-very-severe COPD, no current asthma diagnosis, and either ≥0 (KRONOS) or ≥1 (ETHOS) moderate/severe exacerbations in the prior year. This pooled post hoc analysis evaluated trough forced expiratory volume in 1 second (FEV) and FEV area under the curve from hours 0 to 4 (AUC) change from baseline over 12-24 weeks, moderate/severe exacerbation rates, and St George's Respiratory Questionnaire (SGRQ) total score over 24 weeks with ICS/LAMA/LABA (BGF 320/14.4/10 µg), LAMA/LABA (glycopyrronium/formoterol fumarate dihydrate [GFF] 14.4/10 µg), and ICS/LABA (budesonide/formoterol fumarate dihydrate [BFF] 320/10 µg) in patients with phenotypic features of asthma defined as reversibility to salbutamol and blood eosinophils ≥300 cells/mm. Analyses were not adjusted for multiplicity.
RESULTS
BGF improved trough FEV and FEV AUC versus GFF (least squares mean [LSM] difference [95% confidence interval (CI)] 125 [39-211] and 153 [59-247] mL) and BFF (LSM difference [95% CI] 118 [30-207] and 146 [49-243] mL). Exacerbation rates were estimated to be lower with BGF versus GFF and BFF (respective rate ratios [95% CI] 0.28 [0.19-0.43] and 0.69 [0.45-1.05]) and SGRQ total score was estimated to be improved with BGF versus GFF and BFF (respective LSM differences [95% CI] -5.18 [-8.11 to -2.24] and -1.09 [-4.08 to 1.91]).
CONCLUSION
BGF was estimated to have benefits on lung function, exacerbations, and health-related quality of life versus dual therapies in patients with COPD and phenotypic features of asthma.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02497001 and NCT02465567.
背景
我们评估了布地奈德/格隆溴铵/富马酸福莫特罗二水合物（BGF）的吸入性糖皮质激素/长效毒蕈碱拮抗剂/长效β受体激动剂（ICS/LAMA/LABA）三联疗法与双重LAMA/LABA和ICS/LABA疗法在慢性阻塞性肺疾病（COPD）且具有哮喘表型特征（支气管扩张剂可逆性和血嗜酸性粒细胞升高）但未诊断为哮喘的患者中的疗效，对于这类患者治疗指南有限。
患者和方法
KRONOS（NCT02497001）和ETHOS（NCT02465567）纳入了中度至极重度COPD患者，目前未诊断为哮喘，且前一年有≥0次（KRONOS）或≥1次（ETHOS）中度/重度急性加重。这项汇总的事后分析评估了12 - 24周内，从基线开始的1秒用力呼气容积（FEV）谷值和0至4小时曲线下面积（AUC）变化、中度/重度急性加重率以及24周时圣乔治呼吸问卷（SGRQ）总分，比较了ICS/LAMA/LABA（BGF 320/14.4/10μg）、LAMA/LABA（格隆溴铵/富马酸福莫特罗二水合物[GFF] 14.4/10μg）和ICS/LABA（布地奈德/富马酸福莫特罗二水合物[BFF] 320/10μg）在定义为对沙丁胺醇可逆且血嗜酸性粒细胞≥300个细胞/mm³的哮喘表型特征患者中的疗效。分析未针对多重性进行调整。
结果
与GFF相比，BGF改善了FEV谷值和FEV AUC（最小二乘均值[LSM]差异[95%置信区间（CI）]为125 [39 - 211]和153 [59 - 247] mL），与BFF相比也有改善（LSM差异[95% CI]为118 [30 - 207]和146 [49 - 243] mL）。估计BGF的急性加重率低于GFF和BFF（各自的率比[95% CI]为0.28 [0.19 - 0.43]和0.69 [0.45 - 1.05]），且估计BGF与GFF和BFF相比，SGRQ总分有所改善（各自的LSM差异[95% CI]为 - 5.18 [- 8.11至 - 2.24]和 - 1.09 [- 4.08至1.91]）。
结论
与双重疗法相比，估计BGF对COPD且具有哮喘表型特征的患者的肺功能、急性加重和健康相关生活质量有益。
试验注册
ClinicalTrials.gov NCT02497001和NCT02465567。
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