Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma
Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma
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DOI：
10.1056/nejmoa1804093
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发表时间：
2018-06-28
影响因子：
158.5
通讯作者：
Teper, Ariel
中科院分区：
文献类型：
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作者：
Rabe, Klaus F.;Nair, Parameswaran;Teper, Ariel
背景杜普曲霉是一种完全人类的抗Intterleukin-4受体单克隆抗体，可阻断白介素-4和白介素13信号传导。它在减少严重哮喘患者口服糖皮质激素时的有效性是未知的。Methodswe随机分配了210例口服糖皮质激素治疗的哮喘患者，以接受dupilumab（以300 mg的剂量为300 mg）或每2周接受24周。在随机化之前进行糖皮质激素剂量调整期后，糖皮质激素剂量从第4周至第20周以向下趋势进行调整，然后以稳定的剂量保持4周。主要终点是第24周的糖皮质激素剂量的降低百分比。关键的次要终点是第24周患者的比例，糖皮质激素剂量的降低至少为50％，而患者比例减少了糖皮质激素剂量减少至少5 mg。还评估了使用支气管扩张剂前1秒（FEV 1）的严重加重率和强迫呼气量。在Dupilumab组中，糖皮质激素剂量的百分比变化为-70.1％，在安慰剂组中与-41.9％相比（P
BACKGROUNDDupilumab is a fully human anti-interleukin-4 receptor alpha monoclonal antibody that blocks both interleukin-4 and interleukin-13 signaling. Its effectiveness in reducing oral glucocorticoid use in patients with severe asthma while maintaining asthma control is unknown.METHODSWe randomly assigned 210 patients with oral glucocorticoid-treated asthma to receive add-on dupilumab (at a dose of 300 mg) or placebo every 2 weeks for 24 weeks. After a glucocorticoid dose-adjustment period before randomization, glucocorticoid doses were adjusted in a downward trend from week 4 to week 20 and then maintained at a stable dose for 4 weeks. The primary end point was the percentage reduction in the glucocorticoid dose at week 24. Key secondary end points were the proportion of patients at week 24 with a reduction of at least 50% in the glucocorticoid dose and the proportion of patients with a reduction to a glucocorticoid dose of less than 5 mg per day. Severe exacerbation rates and the forced expiratory volume in 1 second (FEV 1) before bronchodilator use were also assessed.RESULTSThe percentage change in the glucocorticoid dose was -70.1% in the dupilumab group, as compared with -41.9% in the placebo group (P