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Abstract：
BACKGROUND: Japanese guidelines recommend triple inhaled corticosteroid (ICS)/long-acting muscarinic antagonist (LAMA)/long-acting β2-agonist (LABA) therapy in patients with chronic obstructive pulmonary disease (COPD) and no concurrent asthma diagnosis who experience frequent exacerbations and have blood eosinophil (EOS) count ≥ 300 cells/mm3, and in patients with COPD and asthma with continuing/worsening symptoms despite receiving dual ICS/LABA therapy. These post-hoc analyses of the KRONOS study in patients with COPD and without an asthma diagnosis, examine the effects of fixed-dose triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual therapies on lung function and exacerbations based on blood EOS count - focusing on blood EOS count 100 to < 300 cells/mm3 - as a function of exacerbation history and COPD severity.
METHODS: In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12-24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses.
RESULTS: Among patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD.
CONCLUSIONS: These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations.
BACKGROUND: ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).
METHODS: In KRONOS, patients were randomized to receive treatments that included BGF 320/14.4/10 µg, glycopyrronium/formoterol fumarate dihydrate (GFF) 14.4/10 µg, or budesonide/formoterol fumarate dihydrate (BFF) 320/10 µg via metered dose inhaler (two inhalations twice-daily for 24 weeks). These post-hoc analyses assessed changes from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV1) over 12-24 weeks and moderate or severe COPD exacerbations rates over 24 weeks. The KRONOS study was not prospectively powered for these subgroup analyses.
RESULTS: Among patients with blood EOS count 100 to < 300 cells/mm3, least squares mean treatment differences for lung function improvement favored BGF over BFF in patients without an exacerbation history in the past year and in patients with moderate and severe COPD, with observed differences ranging from 62 ml to 73 ml across populations. In this same blood EOS population, moderate or severe exacerbation rates were reduced for BGF relative to GFF by 56% in patients without an exacerbation history in the past year, by 47% in patients with moderate COPD, and by 50% in patients with severe COPD.
CONCLUSIONS: These post-hoc analyses of patients with moderate-to-very severe COPD from the KRONOS study seem to indicate clinicians may want to consider a step-up to triple therapy in patients with persistent/worsening symptoms with blood EOS count > 100 cells/mm3, even if disease severity is moderate and there is no recent history of exacerbations.
BACKGROUND: ClinicalTrials.gov registry number NCT02497001 (registration date, 13 July 2015).
摘要：
背景：日本指南推荐对慢性阻塞性肺疾病（COPD）且无并发哮喘诊断且经历频繁加重且血液嗜酸性粒细胞（EOS）计数≥300个细胞/mm3的慢性阻塞性肺疾病和哮喘患者（尽管接受LABA双重治疗，但仍持续/恶化）的患者，以及慢性阻塞性肺疾病和哮喘患者。这些对患有COPD且没有哮喘诊断的患者的KRONOS研究的事后分析，根据血液EOS计数(重点是血液EOS计数100至<300个细胞/mm3),作为加重史和COPD严重程度的函数,研究固定剂量的布地奈德/格隆铵/福莫特罗二水合物(BGF)三联疗法与双联疗法对肺功能和加重的影响.
方法：在KRONOS中，患者随机接受包括BGF320/14.4/10µg的治疗，富马酸格隆铵/福莫特罗二水合物（GFF）14.4/10µg，或布地奈德/富马酸福莫特罗二水合物（BFF）320/10µg通过计量剂量吸入器（每天两次吸入，持续24周）。这些事后分析评估了12-24周早晨用药前1s用力呼气量（FEV1）和24周中度或重度COPD加重率相对于基线的变化。KRONOS研究对这些亚组分析没有前瞻性的影响。
结果：在血液EOS计数为100至<300个细胞/mm3的患者中，肺功能改善的最小二乘平均治疗差异在过去一年中没有加重史的患者以及中度和重度COPD患者中，BGF优于BFF。观察到的差异范围从62毫升到73毫升。在同样的血液EOS人群中，在过去一年中,无加重史的患者中,BGF的中度或重度加重率相对于GFF降低了56%,47％的中度COPD患者，严重COPD患者的比例为50％。
结论：这些来自KRONOS研究的中度至非常重度COPD患者的事后分析似乎表明，临床医生可能希望考虑对血液EOS计数>100细胞/mm3的持续/恶化症状的患者采用三联疗法，即使疾病严重程度中等且近期没有恶化史。
背景：ClinicalTrials.gov登记号NCT0249701（注册日期，2015年7月13日）。
方法：在KRONOS中，患者随机接受包括BGF320/14.4/10µg的治疗，富马酸格隆铵/福莫特罗二水合物（GFF）14.4/10µg，或布地奈德/富马酸福莫特罗二水合物（BFF）320/10µg通过计量剂量吸入器（每天两次吸入，持续24周）。这些事后分析评估了12-24周早晨用药前1s用力呼气量（FEV1）和24周中度或重度COPD加重率相对于基线的变化。KRONOS研究对这些亚组分析没有前瞻性的影响。
结果：在血液EOS计数为100至<300个细胞/mm3的患者中，肺功能改善的最小二乘平均治疗差异在过去一年中没有加重史的患者以及中度和重度COPD患者中，BGF优于BFF。观察到的差异范围从62毫升到73毫升。在同样的血液EOS人群中，在过去一年中,无加重史的患者中,BGF的中度或重度加重率相对于GFF降低了56%,47％的中度COPD患者，严重COPD患者的比例为50％。
结论：这些来自KRONOS研究的中度至非常重度COPD患者的事后分析似乎表明，临床医生可能希望考虑对血液EOS计数>100细胞/mm3的持续/恶化症状的患者采用三联疗法，即使疾病严重程度中等且近期没有恶化史。
背景：ClinicalTrials.gov登记号NCT0249701（注册日期，2015年7月13日）。
