格隆溴铵/富马酸福莫特罗定量吸入器用于慢性阻塞性肺疾病初治患者的维持治疗：随机 PINNACLE 试验的事后分析。
Glycopyrrolate/formoterol fumarate metered dose inhaler for maintenance-naïve patients with chronic obstructive pulmonary disease: a post-hoc analysis of the randomized PINNACLE trials.
机构信息
State Key Laboratory of Respiratory Disease, National Clinical Research Center of Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
出版信息
Respir Res. 2020 Mar 12;21(1):69. doi: 10.1186/s12931-020-1332-3.
BACKGROUND
Glycopyrrolate (GP)/formoterol fumarate (FF; GFF) metered dose inhaler is a fixed-dose combination dual bronchodilator for patients with chronic obstructive pulmonary disease (COPD); however, whether the efficacy in patients without current maintenance treatment is consistent with currently maintenance-treated patients is unclear.
METHODS
Data from patients who were not maintenance-treated at screening (NMT) (n = 1943) and patients who were maintenance-treated at screening (MT) patients (n = 3040) receiving GFF, FF, GP, or placebo were pooled from the Phase III PINNACLE studies (NCT01854645, NCT01854658, NCT02343458) for post-hoc analysis. MT patients had received long-acting bronchodilators and/or inhaled corticosteroids in the 30 days prior to screening, and/or prior to randomization. NMT patients had received short-acting bronchodilators or no treatment. Outcomes included forced expiratory volume over 1 s (FEV), clinically important deterioration (CID), rescue medication use, and safety.
RESULTS
GFF provided significant lung function improvements at Week 24 versus placebo, GP, and FF for NMT patients, with pre-dose trough FEV treatment differences of 152 (117-188) mL, 73 (45-100) mL, and 56 (29-84) mL, respectively (least squares mean change from baseline versus comparators [95% CI]; all P < 0.0001). GFF reduced the risk of CID by 17-43% in NMT (P ≤ 0.0157) and 18-52% (P ≤ 0.0012) in MT patients compared with monotherapy and placebo, and reduced rescue medication use by 1.5 puffs/day over 24 weeks for both cohorts. Safety profiles for all cohorts were consistent with each other and the parent studies.
CONCLUSIONS
NMT patients achieved better lung function with GFF versus monotherapy and placebo, without increased safety risk. Dual bronchodilator therapy may offer better outcomes than monotherapy for COPD patients when administered as first-line treatment.
背景
格隆溴铵/富马酸福莫特罗（GFF）定量吸入器是一种固定剂量的联合双支气管扩张剂，用于慢性阻塞性肺疾病（COPD）患者；然而，对于没有当前维持治疗的患者，其疗效是否与目前接受维持治疗的患者一致尚不清楚。
方法
从未接受维持治疗的筛选患者（NMT）（n=1943）和接受 GFF、FF、GP 或安慰剂的接受维持治疗的筛选患者（MT）（n=3040）的 PINNACLE III 期研究中（NCT01854645、NCT01854658、NCT02343458）汇集了患者数据，进行了事后分析。MT 患者在筛选前 30 天内已接受长效支气管扩张剂和/或吸入性皮质类固醇治疗，或在随机分组前已接受治疗。NMT 患者接受了短效支气管扩张剂或未接受治疗。主要结局包括用力呼气量（FEV）、临床显著恶化（CID）、急救药物使用和安全性。
结果
与安慰剂、GP 和 FF 相比，GFF 在第 24 周为 NMT 患者提供了显著的肺功能改善，未接受治疗的患者的预剂量谷值 FEV 治疗差异分别为 152（117-188）mL、73（45-100）mL 和 56（29-84）mL（最小二乘均值变化与对照物相比的差异[95%CI]；均 P<0.0001）。与单药治疗和安慰剂相比，GFF 降低了 NMT 患者 CID 的风险 17-43%（P≤0.0157）和 MT 患者 18-52%（P≤0.0012），并在 24 周内减少了 1.5 吸/天的急救药物使用。所有队列的安全性特征与彼此和母体研究一致。
结论
与单药治疗和安慰剂相比，GFF 为 NMT 患者提供了更好的肺功能，而没有增加安全性风险。对于 COPD 患者，当作为一线治疗时，双支气管扩张剂治疗可能比单药治疗提供更好的结局。
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