D'Urzo Anthony D, Rennard Stephen I, Kerwin Edward M, Mergel Victor, Leselbaum Anne R, Caracta Cynthia F
Respir Res. 2014 Oct 14;15(1):123. doi: 10.1186/s12931-014-0123-0.
Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone. The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.
In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*. Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol). Secondary endpoints were change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24. Safety and tolerability were also assessed.
At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001). Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC. Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively. All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.
Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo. Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.
Clinicaltrials.gov NCT01437397.
联合使用两种具有互补作用机制的长效支气管扩张剂可能为慢性阻塞性肺疾病（COPD）患者带来比单独使用任何一种治疗方法更大的治疗益处。本文介绍了长效毒蕈碱拮抗剂阿地溴铵与长效β2受体激动剂富马酸福莫特罗的固定剂量复方制剂（FDC）在中重度COPD患者中的疗效和安全性。
在这项为期24周的双盲研究中，1692例稳定期COPD患者被平均随机分为每日两次接受阿地溴铵400μg/福莫特罗12μg（ACL400/FOR12 FDC）、阿地溴铵400μg/福莫特罗6μg（ACL400/FOR6 FDC）、阿地溴铵400μg、福莫特罗12μg治疗或使用多剂量干粉吸入器（Genuair®/Pressair®）*给予安慰剂治疗。共同主要终点为给药后1小时早晨FEV1从基线至第24周的变化（FDC与阿地溴铵比较）以及早晨给药前（谷值）FEV1从基线至第24周的变化（FDC与福莫特罗比较）。次要终点为圣乔治呼吸问卷（SGRQ）总分从基线的变化以及第24周过渡性呼吸困难指数（TDI）焦点评分的改善情况。同时评估了安全性和耐受性。
研究结束时，接受ACL400/FOR12 FDC或ACL400/FOR6 FDC治疗的患者给药后1小时FEV1较基线的改善显著大于接受阿地溴铵治疗的患者（分别为108mL和87mL；p<0.0001）。接受ACL400/FOR12 FDC治疗的患者谷值FEV1的改善显著大于接受福莫特罗治疗的患者（45mL；p=0.0102），接受ACL400/FOR6 FDC治疗的患者谷值FEV1较福莫特罗有26mL的数值改善。研究结束时，ACL400/FOR12 FDC组的SGRQ总分和TDI焦点评分均有显著改善（p<0.0001），与安慰剂相比的差异分别超过最小临床重要差异≥4分和≥1单位。所有治疗耐受性良好，FDC的安全性与单一疗法相似。
每日两次给予阿地溴铵400μg/福莫特罗12μg FDC治疗可提供快速且持续的支气管扩张，优于单一疗法；与安慰剂相比，呼吸困难和健康状况有显著临床改善。阿地溴铵/福莫特罗FDC可能是COPD患者一种有效且耐受性良好的新治疗选择。
Clinicaltrials.gov NCT01437397。
