Mepolizumab and exacerbations of refractory eosinophilic asthma.
Mepolizumab and exacerbations of refractory eosinophilic asthma.
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DOI：
10.1056/nejmoa0808991
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发表时间：
2009-03-05
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影响因子：
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通讯作者：
Pavord ID
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作者：
Haldar P;Brightling CE;Hargadon B;Gupta S;Monteiro W;Sousa A;Marshall RP;Bradding P;Green RH;Wardlaw AJ;Pavord ID
哮喘的加重与大量的发病率和死亡率以及大量的卫生保健资源的使用有关。预防急性加重仍然是治疗的重要目标。有证据表明，气道嗜酸性粒细胞炎症与急性加重的风险有关。我们对61名患有难治性嗜酸性粒细胞性哮喘并有复发性严重急性发作病史的受试者进行了一项随机、双盲、安慰剂对照、平行组研究。受试者每月接受一次美泊利单抗（抗白细胞介素-5单克隆抗体）（29例受试者）或安慰剂（32例受试者）输注，持续1年。主要结局指标为50周治疗期内每例受试者的重度急性发作次数。次要结局包括哮喘症状的变化、哮喘生活质量问卷评分（AQLQ，评分范围为1至7，较低的值表明损害更严重，0.5个单位的变化被认为具有临床意义）、1秒内用力呼气量（FEV 1）使用支气管扩张剂后、气道高反应性以及血液和痰中的嗜酸性粒细胞计数。在50周的治疗过程中，与安慰剂相比，美泊利珠单抗与严重急性加重显著减少相关（每例受试者平均加重2.0 vs. 3.4;相对风险，0.57; 95%置信区间[CI]，0.32 - 0.92; P = 0.02），AQLQ评分显著改善（较基线平均增加，0.55 vs. 0.19;组间平均差异，0.35; 95% CI，0.08 - 0.62; P = 0.02）。美泊利单抗显著降低血液（P<0.001）和痰（P = 0.002）中的嗜酸性粒细胞计数。两组在症状、使用支气管扩张剂后的FEV 1或气道高反应性方面无显著差异。报告的唯一严重不良事件是因急性重度哮喘住院。美泊利单抗治疗可减少难治性嗜酸性粒细胞性哮喘患者的急性发作并改善AQLQ评分。我们的研究结果表明，嗜酸性粒细胞有一个重要的效应细胞在哮喘严重急性发作的发病机制中的作用，在这个患者群体。（当前对照试验编号，ISRCTN 75169762。）
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. 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 (FEV1) after use of a bronchodilator, airway hyperresponsiveness, and eosinophil counts in the blood and sputum. 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, FEV1 after bronchodilator use, or airway hyperresponsiveness. The only serious adverse events reported were hospitalizations for acute severe asthma. 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. (Current Controlled Trials number, ISRCTN75169762.)