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dupilumab在嗜酸性粒细胞水平升高的持续性哮喘中的应用
Dupilumab in Persistent Asthma with Elevated Eosinophil Levels


Sally Wenzel ... 呼吸系统疾病 • 2013.06.27
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 • 美泊利单抗在嗜酸性粒细胞哮喘中减少口服糖皮质激素用量的作用 • 白三烯拮抗剂作为哮喘控制的一线或添加疗法研究

摘要


背景

中至重度哮喘的治疗效果一直较差。我们评估了dupilumab(SAR231893/REGN668)在持续性、中至重度哮喘并伴有嗜酸性粒细胞水平升高患者中的疗效和安全性,dupilumab是一种白介素-4受体α亚单位的完全性人源性单克隆抗体。

 

方法

我们纳入了患持续性、中至重度哮喘,且每微升血液嗜酸性粒细胞计数至少达到300个或痰嗜酸性粒细胞水平至少达到3%、使用中等剂量至大剂量吸入性糖皮质激素联合长效β受体激动剂(LABA)的患者。我们使用dupilumab(300 mg)或者安慰剂,方法为皮下给药每周1次。指导患者在第4周时停用LABA,并从第6至第9周逐渐减量并最终停用吸入性糖皮质激素。患者接受研究药物治疗12周或者直到发生研究方案定义的哮喘恶化。主要终点是出现哮喘恶化;次要终点包括一系列哮喘控制的测量指标。研究也评估了治疗对多种2型辅助T细胞(Th2)相关生物标志物的作用,以及治疗安全性和耐受性。

 

结果

共计52例患者被分到dupilumab治疗组,52例患者被分到安慰剂组。两组患者的基线特征类似。dupilumab组有3例(6%)患者发生哮喘恶化而安慰剂组有23例发生恶化(44%),对应即dupilumab组有87%的下降(比值比,0.08;95%置信区间[CI],0.02~0.28;P<0.001)。肺功能和哮喘控制的大部分测量指标都观察到了显著好转。dupilumab降低了Th2介导炎症的相关生物标志物。注射部位反应、鼻咽炎、恶心和头痛在dupilumab治疗组比安慰剂组更多见。

 

结论

对于持续性、中至重度哮喘和嗜酸性粒细胞水平升高,并使用吸入性糖皮质激素和LABA的患者,在停用LABA和吸入性糖皮质激素后,dupilumab治疗相比安慰剂可减少哮喘恶化的次数,改善肺功能并降低Th2相关炎症标志物水平(由赛诺菲公司和再生元制药公司[Regeneron Pharmaceuticals]资助,在ClinicalTrails.gov注册号为NCT01312961)。





作者信息

Sally Wenzel, M.D., Linda Ford, M.D., David Pearlman, M.D., Sheldon Spector, M.D., Lawrence Sher, M.D., Franck Skobieranda, M.D., Lin Wang, Ph.D., Stephane Kirkesseli, M.D., Ross Rocklin, M.D., Brian Bock, D.O., Jennifer Hamilton, Ph.D., Jeffrey E. Ming, M.D., Ph.D., Allen Radin, M.D., Neil Stahl, Ph.D., George D. Yancopoulos, M.D., Ph.D., Neil Graham, M.D., and Gianluca Pirozzi, M.D., Ph.D.
From the Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh (S.W.); Asthma and Allergy Center, Bellevue, NE (L.F.); Colorado Allergy and Asthma Centers, Denver (D.P.); California Allergy and Asthma Medical Group, Los Angeles (S.S.); Peninsula Research Associates, Rolling Hills Estates, CA (L.S.); Research and Development, Sanofi, Bridgewater, NJ (F.S., L.W., S.K., R.R., B.B., J.E.M., G.P.); and Regeneron Pharmaceuticals, Tarrytown, NY (J.H., A.R., N.S., G.D.Y., N.G.).Address reprint requests to Dr. Wenzel at 3459 Fifth Ave., NW 628 Montefiore, Pittsburgh, PA 15213, or at wenzelse@upmc.edu.

 

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