IL-5单抗（美泊利单抗）减少激素抵抗型嗜酸细胞性哮喘急性发作
2009/05/18
哮喘急性发作与病死率和医疗费用密切相关。预防急性发作是哮喘治疗的重要目标之一。而气道嗜酸细胞性炎症是哮喘急性发作的一个主要危险因素。Haldar等为观察IL-5单抗（美泊利单抗）阻断嗜酸细胞性炎症对激素抵抗型哮喘患者的治疗作用，对61例激素抵抗型嗜酸细胞性哮喘患者进行了一项为期1年的随机、双盲、安慰剂对照的临床研究。
结果显示：在为期50周的观察中，美泊利单抗较安慰剂组显著减少了重度急性发作的次数（分别为2.0，3.2；相对危险度0.57；95%可信区间0.32-0.92；P=0.02）。美泊利单抗治疗组患者AQLQ评分的改善程度较安慰剂组显著增加（较基线水平平均分别提高0.55，0.19；组间平均差异为0.35；95%可信区间0.08-0.62；P=0.02）。美泊利单抗显著减少了外周血（P<0.001）和痰中（P=0.002）的嗜酸细胞计数。但两组患者在症状、使用支气管扩张剂后的FEV1、气道高反应性三个指标上没有显著差异。本研究观察到的唯一严重不良事件是因急性重症哮喘需住院治疗。
由此可见，美泊利单抗治疗可减少激素抵抗型嗜酸细胞性哮喘患者的急性发作次数，并改善AQLQ评分。在激素抵抗型哮喘急性发作的发病机制中，嗜酸细胞是一种重要的效应
细胞。
（欧阳海峰 第四军医大学西京医院呼吸内科 710032 摘译）
（N Engl J Med. 2009;360(10):985-993）
（N Engl J Med. 2009;360(10):985-993）
Mepolizumab and exacerbations of refractory eosinophilic asthma.
Haldar P, Brightling CE, Hargadon B, Gupta S, Monteiro W, Sousa A, Marshall RP, Bradding P, Green RH, Wardlaw AJ, Pavord ID.
BACKGROUND：Exacerbations of asthma are associated with substantial morbidity and mortality and with considerable use of health care resources. Preventing exacerbations remains an important goal of therapy. There is evidence that eosinophilic inflammation of the airway is associated with the risk of exacerbations.
METHODS：We conducted a randomized, double-blind, placebo-controlled, parallel-group study of 61 subjects who had refractory eosinophilic asthma and a history of recurrent severe exacerbations. Subjects received infusions of either mepolizumab, an anti-interleukin-5 monoclonal antibody (29 subjects), or placebo (32) at monthly intervals for 1 year. The primary outcome measure was the number of severe exacerbations per subject during the 50-week treatment phase. Secondary outcomes included a change in asthma symptoms, scores on the Asthma Quality of Life Questionnaire (AQLQ, in which scores range from 1 to 7, with lower values indicating more severe impairment and a change of 0.5 unit considered to be clinically important), forced expiratory volume in 1 second (FEV(1)) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum.
RESULTS：Mepolizumab was associated with significantly fewer severe exacerbations than placebo over the course of 50 weeks (2.0 vs. 3.4 mean exacerbations per subject; relative risk, 0.57; 95% confidence interval [CI], 0.32 to 0.92; P=0.02) and with a significant improvement in the score on the AQLQ (mean increase from baseline, 0.55 vs. 0.19; mean difference between groups, 0.35; 95% CI, 0.08 to 0.62; P=0.02). Mepolizumab significantly lowered eosinophil counts in the blood (P<0.001) and sputum (P=0.002). There were no significant differences between the groups with respect to symptoms, FEV(1) after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma.
CONCLUSIONS：Mepolizumab therapy reduces exacerbations and improves AQLQ scores in patients with refractory eosinophilic asthma. The results of our study suggest that eosinophils have a role as important effector cells in the pathogenesis of severe exacerbations of asthma in this patient population.
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阻断肿瘤坏死因子α在重症持续哮喘中的随机、双盲、安慰剂对照研究
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口服抗真菌药物治疗真菌致敏性严重哮喘的随机对照研究—FAST
