A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma
A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma
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DOI：
10.1164/rccm.200701-085oc
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发表时间：
2007-12-01
影响因子：
24.7
通讯作者：
Barnes, Neil C.
中科院分区：
文献类型：
--
作者：
Flood-Page, Patrick;Swenson, Cheri;Barnes, Neil C.
理由：哮喘患者支气管粘膜中嗜酸性粒细胞的积聚被认为是哮喘发病机制的核心事件。在动物模型中，针对过敏原挑战的气道嗜酸性粒细胞募集和气道高反应性可通过特异性靶向白细胞介素 5 来减少。之前的一项小剂量探索研究发现美泊利单抗（一种人源化抗白细胞介素 5 单克隆抗体）对人类过敏原激发没有影响。 目的：研究每月 3 次静脉输注美泊利单抗（250 或 750 mg）对 362 名哮喘患者的临床结果测量的影响，尽管吸入皮质类固醇治疗（400-1,000 μg 倍氯米松）但仍出现持续症状方法：多中心、随机、双盲、安慰剂对照研究。测量和主要结果：晨间呼气峰流量、1 秒用力呼气量、每日 β(2) 激动剂使用、症状评分、恶化率和生活质量测量。还测量了由 37 名个体组成的亚组中的痰嗜酸性粒细胞水平。美泊利单抗与两个治疗组中血液和痰中嗜酸性粒细胞显着减少相关（血液，两个剂量的 P < 0.001，痰，250 mg 的 P = 0.006，750 mg 的 P = 0.004）。测量的任何临床终点均没有统计学上的显着变化。美泊利单抗 750 mg 治疗组的急性发作率下降趋势不显着 (P = 0.065)。结论。尽管接受了吸入皮质类固醇治疗，但美泊利单抗治疗似乎并未给症状持续的哮喘患者带来显着的临床益处。需要进一步研究美泊利单抗对急性发作率的影响，使用专门针对伴有持续性气道嗜酸性粒细胞增多的哮喘患者的方案。
Rationale: Accumulation of eosinophils in the bronchial mucosa of individuals with asthma is considered to be a central event in the pathogenesis of asthma. In animal models, airway eosinophil recruitment and airway hyperresponsiveness in response to allergen challenge are reduced by specific targeting of interleukin-5. A previous small dose-finding study found that mepolizumab, a humanized anti-interleukin-5 monoclonal antibody, had no effect on allergen challenge in humans.Objectives: To investigate the effect of three intravenous infusions of mepolizumab, 250 or 750 mg at monthly intervals, on clinical outcome measures in 362 patients with asthma experiencing persistent symptoms despite inhaled corticosteroid therapy (400-1,000 mu g of beclomethasone or equivalent).Methods: Multicenter, randomized, double-blind, placebo-controlled study.Measurements and Main Results: Morning peak expiratory flow, forced expiratory volume in 1 second, daily beta(2)-agonist use, symptom scores, exacerbation rates, and quality of life measures. Sputum eosinophil levels were also measured in a subgroup of 37 individuals. Mepolizumab was associated with a significant reduction in blood and sputum eosinophils in both treatment groups (blood, P < 0.001 for both doses, sputum, P = 0.006 for 250 mg and P = 0.004 for 750 mg). There were no statistically significant changes in any of the clinical end points measured. There was a nonsignificant trend for decrease in exacerbation rates in the mepolizumab 750-mg treatment group (P = 0.065).Conclusions. Mepolizumab treatment does not appear to add significant clinical benefit in patients with asthma with persistent symptoms despite inhaled corticosteroid therapy. Further studies are needed to investigate the effect of mepolizumab on exacerbation rates, using protocols specifically tailored to patients with asthma with persistent airway eosinophilia.