Papi A, Dokic D, Tzimas W, Mészáros I, Olech-Cudzik A, Koroknai Z, McAulay K, Mersmann S, Dalvi P S, Overend T
Department of Internal and CardioRespiratory Medicine, Reseach Center on Asthma and COPD, University of Ferrara, Ferrara, Italy.
Clinic of Pulmology and Allergy, Clinical Centre, Medical Faculty, Ss. Cyril and Methodius University, Skopje, Macedonia.
Int J Chron Obstruct Pulmon Dis. 2017 Jul 5;12:1961-1971. doi: 10.2147/COPD.S136527. eCollection 2017.
To evaluate fluticasone propionate/formoterol (FP/FORM) in COPD.
COPD patients with forced expiratory volume in 1 s (FEV) ≤50% predicted and ≥1 moderate/severe COPD exacerbation in the last 12 months were randomized to FP/FORM 500/20 or 250/10 µg bid, or formoterol (FORM) 12 µg bid for 52 weeks. The primary outcome was the annualized rate of moderate/severe COPD exacerbations.
In total, 1,765 patients were randomized. There were fewer discontinuations with FP/FORM 500/20 µg (20.6%) and 250/10 µg (24.0%) compared with FORM (26.1%). None of the two FP/FORM doses reduced the moderate/severe exacerbation rate versus FORM (rate ratios [RR]: 0.93; ≤0.402). There was a trend toward a lower moderate/severe exacerbation rate with FP/FORM 500/20 µg versus FORM in patients with ≥2 exacerbations in the preceding year (RR: 0.79; =0.084). Pre- and post-dose FEV and forced vital capacity were greater with FP/FORM 500/20 µg versus FORM (≤0.039). There was a trend toward a lower EXAcerbations of Chronic pulmonary disease Tool (EXACT) exacerbation rate with FP/FORM 500/20 µg versus FORM (RR: 0.87; =0.077). There were more St George's Respiratory Questionnaire for COPD (SGRQ-C) responders with FP/FORM 500/20 µg than FORM (odds ratios [OR] at weeks 6, 23 and 52 ≥1.28; ≤0.054). EXACT-respiratory symptoms total and breathlessness scores were lower with both FP/FORM 500/20 µg and 250/10 µg versus FORM (≤0.066). Acute β-agonist-induced effects and 24-hour Holter findings were similar for all treatments. Mean 24-hour urinary cortisol was similarly reduced with both FP/FORM doses. Radiologically confirmed pneumonia was seen in 2.4%, 3.2% and 1.5% of FP/FORM 500/20 µg, FP/FORM 250/10 µg and FORM-treated patients, respectively. Adverse events were otherwise similar across treatment groups.
FP/FORM did not reduce exacerbation rates versus FORM. Numerical benefits were observed with FP/FORM 500/20 µg versus FORM for secondary variables, including lung function, EXACT exacerbations, SGRQ-C and EXACT-respiratory symptoms total and breathlessness scores. Few efficacy differences were evident between FP/FORM 250/10 µg and FORM. Pneumonia was more frequent in FP/FORM-treated patients, although the absolute difference was low. Adverse events were otherwise similar between treatments.
评估丙酸氟替卡松/福莫特罗（FP/FORM）在慢性阻塞性肺疾病（COPD）中的疗效。
将1秒用力呼气容积（FEV）≤预计值的50%且在过去12个月内有≥1次中度/重度COPD急性加重的COPD患者随机分为三组，分别接受500/20或250/10μg bid的FP/FORM治疗，或12μg bid的福莫特罗（FORM）治疗，为期52周。主要结局指标为中度/重度COPD急性加重的年化率。
总共1765例患者被随机分组。与FORM组（26.1%）相比，500/20μg的FP/FORM组（20.6%）和250/10μg的FP/FORM组（24.0%）停药的患者较少。与FORM相比，两种FP/FORM剂量均未降低中度/重度急性加重率（率比[RR]：0.93；P≤0.402）。在前一年有≥2次急性加重的患者中，500/20μg的FP/FORM组与FORM组相比，有降低中度/重度急性加重率的趋势（RR：0.79；P = 0.084）。与FORM相比，500/20μg的FP/FORM组给药前和给药后的FEV和用力肺活量更大（P≤0.039）。与FORM相比，500/20μg的FP/FORM组有降低慢性肺部疾病急性加重工具（EXACT）急性加重率的趋势（RR：0.87；P = 0.077）。在第6、23和52周，500/20μg的FP/FORM组中圣乔治呼吸问卷COPD版（SGRQ-C）有反应者比FORM组更多（优势比[OR]≥1.28；P≤0.054）。与FORM相比，500/20μg和250/10μg的FP/FORM组的EXACT-呼吸症状总分和呼吸困难评分更低（P≤0.066）。所有治疗的急性β受体激动剂诱导效应和24小时动态心电图结果相似。两种FP/FORM剂量使24小时尿皮质醇均值同样降低。在接受500/20μg的FP/FORM、250/10μg的FP/FORM和FORM治疗的患者中，经放射学证实的肺炎发生率分别为2.4%、3.2%和1.5%。各治疗组的不良事件在其他方面相似。
与FORM相比，FP/FORM未降低急性加重率。在包括肺功能、EXACT急性加重、SGRQ-C以及EXACT-呼吸症状总分和呼吸困难评分等次要变量方面，500/20μg的FP/FORM组与FORM相比有一些数值上的益处。250/10μg的FP/FORM组与FORM组之间几乎没有明显的疗效差异。尽管绝对差异较小，但接受FP/FORM治疗的患者肺炎更常见。各治疗组的不良事件在其他方面相似。
