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长效β2受体激动剂治疗哮喘的安全性试验汇总分析
Combined Analysis of Asthma Safety Trials of Long-Acting β2-Agonists


William W. Busse ... 呼吸系统疾病 • 2018.06.28
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LABA终证清白:ICS /LABA治疗在安全性方面不亚于ICS

 

李建雄,徐金富*

同济大学附属上海市肺科医院呼吸与危重症医学科

*通讯作者

 

2018年6月28日出版的《新英格兰医学杂志》(NEJM)刊发的多数据库合并分析文章1,利用四项著名的大规模随机对照临床研究数据,对长效b2受体激动剂(LABA)治疗哮喘的安全性进行了事后分析。数据表明,吸入型糖皮质激素(ICS)/LABA治疗在安全性方面不亚于ICS,LABA终证清白。

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摘要


背景

在一项大型上市后试验中,患者死亡率增加,因此初步识别出了长效β2受体激动剂(LABA)治疗哮喘的安全顾虑。2010年,美国食品药品监督管理局(FDA)要求销售治疗哮喘用LABA的4家公司开展前瞻性、随机、对照试验,在青少年(12~17岁)和成人中,对LABA+吸入型糖皮质激素联合治疗和吸入型糖皮质激素单独治疗的安全性进行比较。这些生产厂家与FDA协作,采用一致的试验方法,从而可以由1个独立的联合监管委员会对4项试验进行最终的汇总分析。

 

方法

作为联合监管委员会的成员,我们对4项试验进行了汇总分析,对吸入型糖皮质激素+LABA(联合治疗)和吸入型糖皮质激素单独治疗进行了比较。主要结局为由哮喘相关插管或死亡构成的复合结局。事后次要结局包括哮喘相关严重事件和哮喘发作。

 

结果

在意向治疗研究包含的36,010例患者中,4例患者出现了3次哮喘相关插管(吸入型糖皮质激素组2次和联合治疗组1次)和2例哮喘相关死亡(均发生在联合治疗组)。在对哮喘相关严重事件(住院、插管或死亡构成的复合事件)的次要分析中,吸入型糖皮质激素组18,006例患者中的108例(0.60%)和联合治疗组18,004例患者中的119例(0.66%)出现了至少1起复合事件(联合治疗组的相对危险度,1.09;95%置信区间[CI],0.83~1.43;P=0.55);吸入型糖皮质激素组的2,100例患者(11.7%)和联合治疗组的1,768例患者(9.8%)出现了至少1次哮喘发作(相对危险度,0.83;95% CI,0.78~0.89;P<0.001)。

 

结论

与吸入型糖皮质激素单独治疗相比,LABA+吸入型糖皮质激素联合治疗未导致哮喘相关严重事件的风险显著增加,但使哮喘发作显著减少。





作者信息

William W. Busse, M.D., Eric D. Bateman, M.B., Ch.B., M.D., Arthur L. Caplan, Ph.D., H. William Kelly, Pharm.D., Paul M. O’Byrne, M.B., Klaus F. Rabe, M.D., Ph.D., and Vernon M. Chinchilli, Ph.D.
From the Department of Medicine, Division of Allergy, Pulmonary and Critical Care Medicine, University of Wisconsin School of Medicine and Public Health, Madison (W.W.B.); the Pulmonary Division, Department of Medicine, University of Cape Town, Cape Town, South Africa (E.D.B.); the Division of Medical Ethics, Department of Population Health, New York University School of Medicine, New York (A.L.C.); the Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque (H.W.K.); the Department of Medicine, McMaster University, Hamilton, ON, Canada (P.M.O.); LungenClinic Grosshansdorf and Christian Albrechts University Kiel, Kiel, and Airway Research Center North, German Center for Lung Research, Grosshansdorf — both in Germany (K.F.R.); and the Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA (V.M.C.). Address reprint requests to Dr. Busse at the University of Wisconsin Hospitals and Clinics, 600 Highland Ave., Madison, WI 53792, or at wwb@medicine.wisc.edu.

 

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