Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma
Oral Glucocorticoid-Sparing Effect of Mepolizumab in Eosinophilic Asthma
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DOI：
10.1056/nejmoa1403291
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发表时间：
2014-09-25
影响因子：
158.5
通讯作者：
Pavord, Ian D.
中科院分区：
文献类型：
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作者：
Bel, Elisabeth H.;Wenzel, Sally E.;Pavord, Ian D.
尽管使用了高剂量吸入疗法，但患有严重哮喘的背景患者仍需要定期用口服糖皮质激素治疗。但是，定期使用全身性糖皮质激素会导致严重且通常是不可逆的不良影响。巨脂蛋白单抗是一种与白介素5结合并失活的人性化的单克隆抗体，已被证明可减少严重嗜酸性嗜酸性哮喘的患者的哮喘患者哮喘患者。一种随机，双盲试验，涉及135例患有严重嗜酸性嗜酸性嗜酸性嗜酸性症状，我们比较了glacocococoliz syporicalsiob（Meparigocococodicals）的随机，双脑性试验（ mg）与安慰剂的服用每4周地皮下施用20周。主要结果是糖皮质激素剂量的降低程度（降低了90％至100％，减少了90％至90％，降低了50％至低于75％，超过0至50％的降低，降低了50％，或者在20至24或戒断中缺乏口服糖皮质激素剂量，或者没有降低口服糖皮质激素剂量。其他结果包括哮喘加重，哮喘控制和安全性的速度。在安慰剂组中，糖皮质激素剂量层降低的可能性比安慰剂组的可能性高2.39倍（95％的置信区间，1.25至4.56; p = 0.008）。在巨脂蛋白分组中，糖皮质激素剂量的基线降低的中位数降低为50％，而安慰剂组没有降低（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临床上重要的区别是0.5点）。大甲珠单抗的安全性与安慰剂的安全性相似。结论性患者需要每天口服糖皮质激素治疗以维持哮喘控制，巨脂蛋白单抗具有显着的糖皮质激素比例疗效，降低了恶化，并改善了哮喘症状的控制。
BACKGROUNDMany 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.METHODSIn 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.RESULTSThe 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.CONCLUSIONSIn 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.