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茚达特罗-格隆溴铵与沙美特罗-氟替卡松治疗COPD的比较研究
Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD


Jadwiga A. Wedzicha ... 呼吸系统疾病 • 2016.06.09
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• 美泊利单抗治疗嗜酸性粒细胞性慢性阻塞性肺疾病 • 单次呼吸量测定是否能准确诊断慢性阻塞性肺疾病 • 氟替卡松联合沙美特罗与单用氟替卡松后的严重哮喘事件比较研究 • 吸入性糖皮质激素撤药与COPD加重 • 噻托溴铵和沙美特罗用于预防COPD加重的比较研究

摘要


背景

对于慢性阻塞性肺疾病(COPD)伴高加重风险的患者,多数指南推荐使用一种长效β受体激动剂(LABA)加一种吸入型糖皮质激素,或使用一种长效毒蕈碱拮抗剂(LAMA)作为首选治疗。但在这类患者中LABA-LAMA发挥的治疗作用尚不明确。

 

方法

我们进行了为期52周的随机、双盲、双模拟非劣效性试验。患COPD且在过去一年中至少有过一次加重病史的患者被随机分组,通过吸入给药分别给予LABA茚达特罗(110 μg)加LAMA格隆溴铵(50 μg),每日一次,或LABA沙美特罗(50 μg)加吸入型糖皮质激素氟替卡松(500 μg),每日两次。主要结局为所有COPD加重的年发生率。

 

结果

共1,680例患者被分入茚达特罗-格隆溴铵组,1,682例患者被分入沙美特罗-氟替卡松组。在降低所有COPD加重的年发生率方面,茚达特罗-格隆溴铵组与沙美特罗-氟替卡松组相比,不仅表现出非劣效性,而且表现出优效性。茚达特罗-格隆溴铵组的年发生率比沙美特罗-氟替卡松组低11%(3.59对4.03;率比,0.89;95%置信区间[CI],0.83~0.96;P=0.003)。茚达特罗-格隆溴铵组的首次加重发生时间比沙美特罗-氟替卡松组晚(71天[95% CI,60~82]对51天[95% CI,46~57];风险比,0.84 [95% CI,0.78~0.91],相当于风险低16%;P<0.001)。茚达特罗-格隆溴铵组中度或重度加重的年发生率比沙美特罗-氟替卡松组低(0.98对1.19;率比,0.83;95% CI,0.75~0.91;P<0.001),且茚达特罗-格隆溴铵组首次发生中度或重度加重的时间比茚达特罗-格隆溴铵组晚(风险比,0.78;95% CI,0.70~0.86;P<0.001),首次发生重度加重的时间也比茚达特罗-格隆溴铵组晚(风险比,0.81;95% CI,0.66~1.00;P=0.046)。茚达特罗-格隆溴铵和沙美特罗-氟替卡松相比,对COPD加重率的作用与基线血嗜酸性粒细胞计数无关。两组的不良事件发生率和死亡率均近似。茚达特罗-格隆溴铵组和沙美特罗-氟替卡松组中肺炎的发生率分别为3.2%和4.8%(P=0.02)。

 

结论

与沙美特罗-氟替卡松相比,在过去一年中有加重病史的COPD患者中,茚达特罗-格隆溴铵能更有效地预防COPD加重(由诺华公司资助,FLAME在ClinicalTrials.gov注册号为NCT01782326)。





作者信息

Jadwiga A. Wedzicha, M.D., Donald Banerji, M.D., Kenneth R. Chapman, M.D., Jørgen Vestbo, M.D., D.M.Sc., Nicolas Roche, M.D., R. Timothy Ayers, M.Sc., Chau Thach, Ph.D., Robert Fogel, M.D., Francesco Patalano, M.D., and Claus F. Vogelmeier, M.D., for the FLAME Investigators*
From the National Heart and Lung Institute, Imperial College London, London (J.A.W.), and the Centre for Respiratory Medicine and Allergy, University of Manchester and University Hospital South Manchester NHS Foundation Trust, Manchester (J.V.) — all in the United Kingdom; Novartis Pharmaceuticals, East Hanover, NJ (D.B., R.T.A., C.T., R.F.); Asthma and Airway Centre, University Health Network and University of Toronto, Toronto (K.R.C.); Service de Pneumologie Assistance Publique–Hôpitaux de Paris, University Paris Descartes (EA2511), Paris (N.R.); Novartis Pharma AG, Basel, Switzerland (F.P.); and the Department of Medicine, Pulmonary and Critical Care Medicine, University Medical Center Giessen and Marburg, Philipps-Universität Marburg, Marburg, Germany (C.F.V.).Address reprint requests to Dr. Wedzicha at the COPD Research Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, Dovehouse St., London SW3 6LY, United Kingdom, or at j.wedzicha@imperial.ac.uk. *A complete list of investigators in the FLAME trial is provided in the Supplementary Appendix, available at NEJM.org.

 

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