美泊利珠单抗在嗜酸性粒细胞性哮喘中的口服糖皮质激素节省作用。
Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma.
机构信息
From the Department of Respiratory Medicine, Academic Medical Center, University of Amsterdam, Amsterdam (E.H.B.); the Department of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Asthma Institute at the University of Pittsburgh Medical Center-University of Pittsburgh School of Medicine, Pittsburgh (S.E.W.); the Lung Institute of Western Australia, Nedlands, and the Centre for Asthma, Allergy and Respiratory Research, University of Western Australia, Crawley - both in Australia (P.J.T.); Respiratory Therapeutic Area, GlaxoSmithKline, Research Triangle Park, NC (C.M.P., S.W.Y., H.G.O.); and Clinical Statistics, GlaxoSmithKline, Stockley Park (O.N.K.), and the Respiratory Medicine Unit, Nuffield Department of Medicine, University of Oxford, Oxford (I.D.P.) - both in the United Kingdom.
出版信息
N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.
BACKGROUND
Many patients with severe asthma require regular treatment with oral glucocorticoids despite the use of high-dose inhaled therapy. However, the regular use of systemic glucocorticoids can result in serious and often irreversible adverse effects. Mepolizumab, a humanized monoclonal antibody that binds to and inactivates interleukin-5, has been shown to reduce asthma exacerbations in patients with severe eosinophilic asthma.
METHODS
In a randomized, double-blind trial involving 135 patients with severe eosinophilic asthma, we compared the glucocorticoid-sparing effect of mepolizumab (at a dose of 100 mg) with that of placebo administered subcutaneously every 4 weeks for 20 weeks. The primary outcome was the degree of reduction in the glucocorticoid dose (90 to 100% reduction, 75 to less than 90% reduction, 50 to less than 75% reduction, more than 0 to less than 50% reduction, or no decrease in oral glucocorticoid dose, a lack of asthma control during weeks 20 to 24, or withdrawal from treatment). Other outcomes included the rate of asthma exacerbations, asthma control, and safety.
RESULTS
The likelihood of a reduction in the glucocorticoid-dose stratum was 2.39 times greater in the mepolizumab group than in the placebo group (95% confidence interval, 1.25 to 4.56; P=0.008). The median percentage reduction from baseline in the glucocorticoid dose was 50% in the mepolizumab group, as compared with no reduction in the placebo group (P=0.007). Despite receiving a reduced glucocorticoid dose, patients in the mepolizumab group, as compared with those in the placebo group, had a relative reduction of 32% in the annualized rate of exacerbations (1.44 vs. 2.12, P=0.04) and a reduction of 0.52 points with respect to asthma symptoms (P=0.004), as measured on the Asthma Control Questionnaire 5 (in which the minimal clinically important difference is 0.5 points). The safety profile of mepolizumab was similar to that of placebo.
CONCLUSIONS
In patients requiring daily oral glucocorticoid therapy to maintain asthma control, mepolizumab had a significant glucocorticoid-sparing effect, reduced exacerbations, and improved control of asthma symptoms. (Funded by GlaxoSmithKline; SIRIUS ClinicalTrials.gov number, NCT01691508.).
背景
许多严重哮喘患者需要定期接受口服糖皮质激素治疗，尽管他们使用了高剂量吸入疗法。然而，常规使用全身糖皮质激素会导致严重且常常不可逆转的不良反应。美泊利珠单抗是一种人源化单克隆抗体，可结合并失活白细胞介素-5，已被证明可减少严重嗜酸性粒细胞性哮喘患者的哮喘恶化。
方法
在一项涉及 135 名严重嗜酸性粒细胞性哮喘患者的随机、双盲试验中，我们比较了美泊利珠单抗（剂量为 100mg）与安慰剂的糖皮质激素节省效果，两种药物均每 4 周皮下注射一次，共 20 周。主要结局是糖皮质激素剂量减少的程度（90%至 100%减少、75%至小于 90%减少、50%至小于 75%减少、大于 0%至小于 50%减少或口服糖皮质激素剂量无减少、20 至 24 周期间哮喘控制不佳或退出治疗）。其他结局包括哮喘恶化率、哮喘控制情况和安全性。
结果
与安慰剂组相比，美泊利珠单抗组糖皮质激素剂量减少的可能性高 2.39 倍（95%置信区间，1.25 至 4.56；P=0.008）。美泊利珠单抗组的糖皮质激素剂量较基线的中位数降低 50%，而安慰剂组则无降低（P=0.007）。尽管接受了减少的糖皮质激素剂量，但与安慰剂组相比，美泊利珠单抗组患者的哮喘恶化年发生率相对降低了 32%（1.44 比 2.12，P=0.04），哮喘症状也降低了 0.52 分（根据哮喘控制问卷 5 评估，最小临床重要差异为 0.5 分）（P=0.004）。美泊利珠单抗的安全性与安慰剂相似。
结论
在需要每日口服糖皮质激素治疗以维持哮喘控制的患者中，美泊利珠单抗具有显著的糖皮质激素节省作用，可减少恶化并改善哮喘症状的控制。（由葛兰素史克公司资助；SIRIUS 临床试验.gov 编号，NCT01691508。）
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