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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
Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease


Ian D. Pavord ... 呼吸系统疾病 • 2017.10.26
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摘要


背景

存在嗜酸性粒细胞表型的慢性阻塞性肺疾病(COPD)患者可能从美泊利单抗(mepolizumab)这种直接作用于白介素-5的单克隆抗体治疗中获益。

 

方法

我们开展了两项3期、随机、安慰剂对照、双盲、平行组临床试验,在使用以吸入型糖皮质激素为基础的三联维持疗法时存在中度或重度加重史的COPD患者中,比较美泊利单抗(METREX中100 mg,METREO中100或300 mg)和安慰剂每4周1次皮下注射,连续给药52周的治疗结局。在METREX中,在存在嗜酸性粒细胞表型的改良意向性治疗人群中,我们对未经选择的患者根据血液嗜酸性粒细胞计数(筛选时≥150/mm3或前一年≥300/mm3)进行分层。在METREO中,所有患者筛选时血液嗜酸性粒细胞计数至少为150/mm3或前一年至少为300/mm3。研究主要终点是年中度或重度加重率,同时也评估安全性。

 

结果

在METREX中,在存在嗜酸性粒细胞表型的改良意向性治疗人群(462例患者)中,美泊利单抗组平均年中度或重度加重率为每年1.40,而安慰剂组为每年1.71(率比,0.82;95%置信区间[CI],0.68~0.98,校正P=0.04)。在总体改良意向性治疗人群(836例患者)中未发现显著组间差异(率比,0.98;95% CI,0.85~1.12;校正P>0.99)。在METREO中,100 mg美泊利单抗组平均年中度或重度加重率为每年1.19,300 mg美泊利单抗组为每年1.27,而安慰剂组为每年1.49。与安慰剂组相比,100 mg和300 mg美泊利单抗组的加重率比分别为0.80(95% CI,0.65~0.98;校正P=0.07)和0.86(95% CI,0.70~1.05;校正P=0.14)。筛选时血液嗜酸性粒细胞计数较高的患者中,与安慰剂相比,美泊利单抗对年中度或重度加重率的影响较大。美泊利单抗安全性特征与安慰剂相似。

 

结论

在存在嗜酸性粒细胞表型的COPD患者中,与安慰剂相比,100 mg剂量美泊利单抗与平均年中度或重度加重率降低相关。该发现提示嗜酸性粒细胞气道炎症在COPD加重中发挥作用(由葛兰素史克资助;METREX和METREO在ClinicalTrials.gov注册号为NCT02105948和NCT02105961)。





作者信息

Ian D. Pavord, D.M., Pascal Chanez, M.D., Ph.D., Gerard J. Criner, M.D., Huib A.M. Kerstjens, M.D., Ph.D., Stephanie Korn, M.D., Ph.D., Njira Lugogo, M.D., Jean-Benoit Martinot, M.D., Hironori Sagara, M.D., Ph.D., Frank C. Albers, M.D., Ph.D., Eric S. Bradford, M.D., Stephanie S. Harris, B.Sc., Bhabita Mayer, M.Sc., David B. Rubin, M.D., Steven W. Yancey, M.Sc., and Frank C. Sciurba, M.D.
From the Respiratory Medicine Unit and Oxford Respiratory Biomedical Research Centre, Nuffield Department of Medicine, University of Oxford, Oxford (I.D.P.), and Clinical Statistics, GlaxoSmithKline, Uxbridge (B.M.) — both in the United Kingdom; the Department of Respiratory Medicine and CIC Nord, Aix-Marseille University, Marseille, France (P.C.); the Department of Thoracic Medicine and Surgery, Lewis Katz School of Medicine at Temple University, Philadelphia (G.J.C.); the Department of Pulmonary Medicine and Tuberculosis, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands (H.A.M.K.); the Pulmonary Department, Mainz University Hospital, Mainz, Germany (S.K.); the Division of Pulmonary, Allergy, and Critical Care Medicine, Duke University, Durham (N.L.), and the Respiratory Medical Franchise (F.C.A.) and the Respiratory Therapeutic Area (E.S.B., S.S.H., D.B.R., S.W.Y.), GlaxoSmithKline, Research Triangle Park — all in North Carolina; the Department of Pneumology, Centre Hospitalier Universitaire–Université Catholique de Louvain, Namur, Namur, Belgium (J.-B.M.); the Division of Allergology and Respiratory Medicine, Showa University School of Medicine, Tokyo (H.S.); and the Department of Medicine, University of Pittsburgh, Pittsburgh (F.C.S.). Address reprint requests to Dr. Sciurba at the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 3471 Fifth Ave., Suite 1211, Pittsburgh, PA 15213, or at sciurbafc@upmc.edu.

 

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