Biomarkers for severe eosinophilic asthma

被引:205
作者
Yancey, Steven W. [1 ]
Keene, Oliver N. [3 ]
Albers, Frank C. [2 ]
Ortega, Hector [1 ]
Bates, Stewart [4 ]
Bleecker, Eugene R. [5 ]
Pavord, Ian [6 ,7 ]
机构
[1] GlaxoSmithKline, Resp Therapeut Area, Res Triangle Pk, NC USA
[2] GlaxoSmithKline, Resp Med Franchise, Res Triangle Pk, NC USA
[3] GlaxoSmithKline, Clin Stat, Stockley Pk, Uxbridge, Middx, England
[4] GlaxoSmithKline, Resp Discovery Med, Stevenage, Herts, England
[5] Univ Arizona, Coll Med, Div Genet Genom & Personalized Med, Tucson, AZ USA
[6] Univ Oxford, Resp Med Unit, Nuffield Dept Med, Oxford, England
[7] Univ Oxford, Oxford Resp BRC, Nuffield Dept Med, Oxford, England
关键词
Eosinophils; biomarkers; severe eosinophilic asthma; ANTI-IL-5 MEPOLIZUMAB THERAPY; OBSTRUCTIVE PULMONARY-DISEASE; SURROGATE END-POINTS; DOUBLE-BLIND; MONOCLONAL-ANTIBODY; SPUTUM EOSINOPHILIA; AIRWAY INFLAMMATION; PLACEBO; BENRALIZUMAB; MARKERS;
D O I
10.1016/j.jaci.2017.10.005
中图分类号
R392 [医学免疫学];
学科分类号
100102 ;
摘要
The last decade has seen the approval of several new biologics for the treatment of severe asthma-targeting specific endotypes and phenotypes. This review will examine how evidence generated from the mepolizumab clinical development program showed that blood eosinophil counts, rather than sputum or tissue eosinophil counts, evolved as a pharmacodynamic and predictive biomarker for the efficacy of treatment with mepolizumab in patients with severe eosinophilic asthma. Based on the available evidence and combined with clinical judgement, a baseline blood eosinophil threshold of 150 cells/mL or greater or a historical blood eosinophil threshold of 300 cells/mL or greater will allow selection of patients with severe eosinophilic asthma who are most likely to achieve clinically significant reductions in the rate of exacerbations with mepolizumab treatment.
引用
收藏
页码:1509 / 1518
页数:10
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