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美泊利单抗在嗜酸性粒细胞哮喘中减少口服糖皮质激素用量的作用
Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma


Elisabeth H. Bel ... 呼吸系统疾病 • 2014.09.25
相关阅读
• 治疗哮喘的另外一种新生物制剂 • dupilumab治疗中至重度未得到控制的哮喘的疗效和安全性 • dupilumab治疗糖皮质激素依赖型重度哮喘的疗效和安全性 • 美泊利单抗治疗嗜酸性粒细胞性慢性阻塞性肺疾病 • dupilumab在嗜酸性粒细胞水平升高的持续性哮喘中的应用

摘要



背景

许多有重度哮喘的患者尽管使用了大剂量的吸入性糖皮质激素,但还需要常规口服糖皮质激素治疗。然而,常规使用全身性糖皮质激素治疗可导致严重和通常不可逆的不良反应。美泊利单抗是一种结合白细胞介素-5并使其失活的人源化单克隆抗体,研究已显示美泊利单抗可减少重度嗜酸性粒细胞哮喘患者的哮喘恶化。

 

方法

我们进行了一项随机、双盲试验,纳入了135例有重度嗜酸性粒细胞哮喘的患者,比较了美泊利单抗(100 mg)与安慰剂相比在减少糖皮质激素用量方面的作用,给药方式为皮下注射,每4周一次,共20周。主要结局指标是糖皮质激素用量的减少程度(糖皮质激素用量减少90%~100%、减少75%~<90%、减少50%~<75%、减少>0~<50%,或者无减少;第20~24周哮喘未得到控制;或退出研究)。其他结局指标包括哮喘恶化的速度、哮喘控制和安全性。

 

结果

美泊利单抗治疗后,糖皮质激素剂量层降低的概率为安慰剂治疗后的2.39倍[95%置信区间(CI):1.25~4.56;P=0.008]。美泊利单抗组糖皮质激素用量相对于基线的中位下降百分比为50%,而安慰剂组中无下降(P=0.007)。尽管接受了剂量更低的糖皮质激素治疗,但美泊利单抗组的患者相比安慰剂组的患者,恶化的年发生率相对下降了32%(1.44对2.12,P=0.04),且根据哮喘控制问卷5(Asthma Control Questionnaire 5,最小临床重要差异为0.5分)评估的哮喘症状下降了0.52分(P=0.004)。美泊利单抗的安全性与安慰剂相似。

 

结论

对于需要每日口服糖皮质激素治疗来维持哮喘控制的患者,美泊利单抗具有显著减少糖皮质激素用量的效果,且减少了恶化,改善了哮喘症状的控制 (由葛兰素史克公司资助,SIRIUS在ClinicalTrails.gov注册号为NCT01691508)。





作者信息

Elisabeth H. Bel, M.D., Ph.D., Sally E. Wenzel, M.D., Philip J. Thompson, M.D., Charlene M. Prazma, Ph.D., Oliver N. Keene, M.Sc., Steven W. Yancey, M.Sc., Hector G. Ortega, M.D., Sc.D., and Ian D. Pavord, D.M., for the SIRIUS Investigators*
From the Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (E.H.B.); the Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Asthma Institute at the University of Pittsburgh Medical Center–University of Pittsburgh School of Medicine, Pittsburgh (S.E.W.); the Lung Institute of Western Australia, Nedlands, and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Crawley — both in Australia (P.J.T.); Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, NC (C.M.P., S.W.Y., H.G.O.); and Clinical Statistics, GlaxoSmithKline, Stockley Park (O.N.K.), and the Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford (I.D.P.) — both in the United Kingdom.Address reprint requests to Dr. Bel at the Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands, or at e.h.bel@amc.uva.nl. *Investigators in the Steroid Reduction with Mepolizumab Study (SIRIUS) are listed in the Supplementary Appendix, available at NEJM.org

 

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