Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis
Dupilumab Treatment in Adults with Moderate-to-Severe Atopic Dermatitis
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DOI：
10.1056/nejmoa1314768
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发表时间：
2014-07-10
影响因子：
158.5
通讯作者：
Radin, Allen R.
中科院分区：
文献类型：
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作者：
Beck, Lisa A.;Thaci, Diamant;Radin, Allen R.
Dupilumab是一种阻断白细胞介素-4和白细胞介素-13的全人单克隆抗体，已在哮喘和嗜酸性粒细胞水平升高的患者中显示出疗效。dupilumab阻断这些2型辅助性T细胞（Th 2）介导的炎症的关键驱动因素可能有助于治疗相关疾病，包括特应性皮炎。方法我们进行了随机、双盲、安慰剂对照试验，涉及患有中度至重度特应性皮炎的成年人，尽管接受了局部糖皮质激素和钙调磷酸酶抑制剂治疗。在两项4周试验和一项12周试验中评价了Dupilumab单药治疗，在另一项4周研究中评价了Dupilumab与外用糖皮质激素联合治疗。终点包括湿疹面积和严重程度指数（EASI）评分、研究者的总体评估评分、瘙痒、安全性评估、血清生物标志物水平和疾病转录组。在为期4周的单药治疗研究中，dupilumab导致临床指数、生物标志物水平和转录组的快速和剂量依赖性改善。dupilumab单药治疗的12周研究结果重现并扩展了4周研究结果：dupilumab组85%的患者，与安慰剂组35%的患者相比，EASI评分降低50%（EASI-50，EASI评分越高表明湿疹的严重程度越高）（P
BACKGROUNDDupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation could help in the treatment of related diseases, including atopic dermatitis.METHODSWe performed randomized, double-blind, placebo-controlled trials involving adults who had moderate-to-severe atopic dermatitis despite treatment with topical glucocorticoids and calcineurin inhibitors. Dupilumab was evaluated as monotherapy in two 4-week trials and in one 12-week trial and in combination with topical glucocorticoids in another 4-week study. End points included the Eczema Area and Severity Index (EASI) score, the investigator's global assessment score, pruritus, safety assessments, serum biomarker levels, and disease transcriptome.RESULTSIn the 4-week monotherapy studies, dupilumab resulted in rapid and dose-dependent improvements in clinical indexes, biomarker levels, and the transcriptome. The results of the 12-week study of dupilumab monotherapy reproduced and extended the 4-week findings: 85% of patients in the dupilumab group, as compared with 35% of those in the placebo group, had a 50% reduction in the EASI score (EASI-50, with higher scores in the EASI indicating greater severity of eczema) (P