D'Urzo Anthony D, Singh Dave, Donohue James F, Kerwin Edward M, Ribera Anna, Molins Eduard, Chuecos Ferran, Jarreta Diana, Gil Esther Garcia
Department of Family and Community Medicine, Faculty of Medicine, University of Toronto, Toronto, ON, Canada,
Medicines Evaluation Unit, Manchester University NHS Foundation Trust, Manchester, UK.
Int J Chron Obstruct Pulmon Dis. 2019 Feb 26;14:479-491. doi: 10.2147/COPD.S185502. eCollection 2019.
Aclidinium/formoterol 400/12 µg is a twice-daily maintenance bronchodilator for COPD. This post hoc study evaluated aclidinium/formoterol vs aclidinium 400 µg, formoterol 12 µg, or placebo in patient subgroups.
Data were pooled from two 24-week Phase III clinical trials (ACLIFORM and AUGMENT). Patients (N=3,394) were analyzed by baseline airflow obstruction severity (moderate/severe), age (<65/≥65 years), sex, and exacerbation history (0/≥1 exacerbation in the previous 12 months). Changes from baseline vs placebo and mono-therapies were evaluated: morning pre-dose (trough) and morning 1-hour post-dose FEV, Transition Dyspnea Index (TDI), and moderate/severe exacerbation rates (healthcare resource utilization [HCRU] and EXAcerbations of Chronic pulmonary disease Tool [EXACT] criteria).
Aclidinium/formoterol improved the post-dose FEV vs placebo and monotherapy in all subgroups (all <0.01) and trough FEV vs placebo (<0.001) and formoterol (<0.05) across all subgroups. Improvements in trough FEV were observed vs aclidinium in patients with severe airflow obstruction, patients aged <65 years, males, and patients with exacerbation history (<0.05). Improvements in TDI were observed vs placebo in all subgroups (all <0.001), monotherapies for patients with moderate (formoterol <0.05) or severe airflow obstruction (aclidinium <0.05), patients aged <65 years (aclidinium <0.01, formoterol <0.05), males (formoterol <0.05), and patients with no exacerbation history (formoterol <0.05). HCRU exacerbation rates were lower for aclidinium/formoterol vs placebo in patients with no exacerbation history (<0.01). EXACT exacerbation rates were lower for aclidinium/formoterol in patients with moderate airflow obstruction vs placebo and aclidinium, patients aged <65 years vs placebo and ≥65 years vs formoterol, males vs placebo, and patients with no exacerbation history vs placebo (all <0.05).
Aclidinium/formoterol significantly improved post-dose FEV, trough FEV, and TDI vs placebo across all subgroups and vs monotherapy in many subgroups. These findings further support the benefits of aclidinium/formoterol for all patients with COPD.
阿地溴铵/福莫特罗400/12微克是一种用于慢性阻塞性肺疾病（COPD）的每日两次维持性支气管扩张剂。这项事后分析研究评估了阿地溴铵/福莫特罗与阿地溴铵400微克、福莫特罗12微克或安慰剂在患者亚组中的疗效。
数据来自两项为期24周的III期临床试验（ACLIFORM和AUGMENT）。患者（N = 3394）按基线气流阻塞严重程度（中度/重度）、年龄（<65/≥65岁）、性别和加重病史（前12个月内0/≥1次加重）进行分析。评估了与安慰剂和单一疗法相比的基线变化：早晨给药前（谷值）和早晨给药后1小时的第一秒用力呼气容积（FEV）、过渡性呼吸困难指数（TDI）以及中度/重度加重率（医疗资源利用[HCRU]和慢性肺病加重工具[EXACT]标准）。
在所有亚组中，阿地溴铵/福莫特罗与安慰剂和单一疗法相比，给药后FEV均有所改善（均<0.01），与安慰剂相比，所有亚组的谷值FEV均有所改善（<0.001），与福莫特罗相比部分亚组有所改善（<0.05）。在气流阻塞严重的患者、年龄<65岁的患者、男性患者以及有加重病史的患者中，与阿地溴铵相比，谷值FEV有所改善（<0.05）。在所有亚组中，与安慰剂相比，TDI均有所改善（均<0.001）；在气流阻塞中度（福莫特罗<0.05）或重度（阿地溴铵<0.05）的患者、年龄<65岁的患者（阿地溴铵<0.01，福莫特罗<0.05）、男性患者（福莫特罗<0.05）以及无加重病史的患者（福莫特罗<0.05）中，与单一疗法相比TDI有所改善。在无加重病史的患者中，阿地溴铵/福莫特罗的HCRU加重率低于安慰剂（<0.01）。在气流阻塞中度的患者中，与安慰剂和阿地溴铵相比，阿地溴铵/福莫特罗的EXACT加重率较低；在年龄<65岁的患者中，与安慰剂相比，在年龄≥65岁的患者中与福莫特罗相比，阿地溴铵/福莫特罗的EXACT加重率较低；在男性患者中与安慰剂相比，在无加重病史的患者中与安慰剂相比，阿地溴铵/福莫特罗的EXACT加重率较低（均<0.05）。
在所有亚组中，与安慰剂相比，阿地溴铵/福莫特罗显著改善了给药后FEV、谷值FEV和TDI，在许多亚组中与单一疗法相比也有改善。这些发现进一步支持了阿地溴铵/福莫特罗对所有COPD患者的益处。
