Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No. 2, East Yinghua Street, Chaoyang District, Beijing, 100029, China.
Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China.
Adv Ther. 2020 Apr;37(4):1591-1607. doi: 10.1007/s12325-020-01266-5. Epub 2020 Mar 6.
This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).
Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.6 μg, budesonide/formoterol fumarate (BFF) MDI 320/9.6 μg, or budesonide/formoterol fumarate dry powder inhaler (BUD/FORM DPI) 400/12 μg twice daily for 24 weeks. The primary endpoint was change from baseline in morning pre-dose trough forced expiratory volume in 1 s (FEV) over weeks 12-24. Secondary endpoints included symptoms, health-related quality of life, and safety. Rate of moderate/severe COPD exacerbations was an additional efficacy endpoint.
In the China subgroup (n = 432; 22.7% of the KRONOS population), BGF MDI demonstrated nominally significant improvements in the primary endpoint versus BFF MDI (least squares mean (LSM) difference 68 mL; P = 0.0035) and BUD/FORM DPI (LSM difference 78 mL; P = 0.0010) but not GFF MDI (LSM difference - 4 mL; P = 0.8316). BGF MDI demonstrated at least numerical improvements versus comparators in secondary lung function and symptom endpoints. BGF MDI reduced the rate of moderate/severe COPD exacerbations versus GFF MDI (rate ratio 0.41; P = 0.0030), with numerical benefits versus BFF MDI and BUD/FORM DPI. All treatments were well tolerated.
Results demonstrated that BGF MDI showed benefits on lung function (vs inhaled corticosteroid/long-acting β-agonist), as well as symptoms and exacerbations relative to dual therapies. Findings support BGF MDI use in Chinese patients with moderate to very severe COPD.
ClinicalTrials.gov NCT02497001.
本预先设定的亚组分析评估了布地奈德/格隆溴铵/福莫特罗富马酸盐定量吸入器（BGF MDI）三联疗法与中度至重度慢性阻塞性肺疾病（COPD）患者 III 期、双盲 KRONOS 研究中国亚组中相应的双联疗法相比的疗效和安全性。
患者按 2:2:1:1 的比例随机分配至 BGF MDI 320/18/9.6μg、格隆溴铵/福莫特罗富马酸盐（GFF）MDI 18/9.6μg、布地奈德/福莫特罗富马酸盐（BFF）MDI 320/9.6μg 或布地奈德/福莫特罗富马酸盐干粉吸入剂（BUD/FORM DPI）400/12μg，每日 2 次，治疗 24 周。主要终点是从第 12-24 周的晨预剂量谷值 1 秒用力呼气容积（FEV）的基线变化。次要终点包括症状、健康相关生活质量和安全性。中度/重度 COPD 加重率是额外的疗效终点。
在中国亚组（n=432；KRONOS 人群的 22.7%）中，与 BFF MDI（最小二乘均数（LSM）差异 68mL；P=0.0035）和 BUD/FORM DPI（LSM 差异 78mL；P=0.0010）相比，BGF MDI 治疗在主要终点显示出名义上的显著改善，但与 GFF MDI 相比无差异（LSM 差异-4mL；P=0.8316）。与对照相比，BGF MDI 至少在次要肺功能和症状终点方面表现出数值改善。与 GFF MDI 相比，BGF MDI 降低了中度/重度 COPD 加重率（发生率比 0.41；P=0.0030），与 BFF MDI 和 BUD/FORM DPI 相比也有数值获益。所有治疗均耐受良好。
结果表明，与吸入性皮质类固醇/长效β-激动剂相比，BGF MDI 在肺功能（vs）以及症状和加重方面显示出益处，与双疗法相比具有优势。结果支持在中国中重度 COPD 患者中使用 BGF MDI。
ClinicalTrials.gov NCT02497001。
