Background

Tezepelumab (AMG 157/MEDI9929), a first-in-class monoclonal antibody, targets thymic stromal lymphopoietin, a cytokine that is implicated in the pathogenesis of atopic dermatitis (AD).

Objective

We sought to evaluate the efficacy and safety of tezepelumab in adults with moderate to severe AD.

Methods

In this phase 2a study (NCT02525094), 113 patients were randomized 1:1 to subcutaneous tezepelumab 280 mg or placebo every 2 weeks, plus class 3 topical corticosteroids (TCS). The primary endpoint was the week 12 response rate for a ≥50% reduction in the Eczema Area and Severity Index (EASI50). Secondary endpoints including EASI75, Investigator's Global Assessment, SCORAD 50, SCORAD 75, pruritus numeric rating and 5-D itch scales, and exploratory endpoints (including EASI90) were assessed at weeks 12, and 16 (post hoc).

Results

A numerically greater percentage of tezepelumab plus TCS-treated patients achieved EASI50 (64.7%) versus placebo plus TCS (48.2%; P = .091). Numerical improvements over placebo were demonstrated for week 12 secondary and exploratory endpoints, with further improvements at week 16. Treatment-emergent adverse events were similar between treatment groups.

Limitations

Greater than expected response rates in placebo-treated patients were possibly attributable to TCS.

Conclusion

Although not statistically significant, numerical improvements over placebo for all week 12 endpoints were demonstrated, with greater week 16 responses.

中文翻译：

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Tezepelumab，一种抗胸腺基质淋巴细胞生成素单克隆抗体，用于治疗中度至重度特应性皮炎：一项随机的2a期临床试验

背景

Tezepelumab（AMG 157 / MEDI9929）是一流的单克隆抗体，靶向胸腺基质淋巴细胞生成素，这是一种与特应性皮炎（AD）发病机理有关的细胞因子。

客观的

我们试图评估tezepelumab在中度至重度AD成人中的疗效和安全性。

方法

在此2a期研究（NCT02525094）中，每2周将113例患者按1：1比例随机分配至280 mg替泽贝单抗或安慰剂皮下注射，另加3类局部皮质类固醇（TCS）。主要终点指标是第12周的缓解率，使湿疹面积和严重程度指数（EASI50）降低≥50％。在第12周和第16周（事后）评估了次要终点，包括EASI75，研究者的总体评估，SCORAD 50，SCORAD 75，瘙痒症数字评分和5-D瘙痒量表以及探索性终点（包括EASI90）。

结果

与安慰剂加TCS（48.2％; P  = .091）相比，用tezepelumab + TCS治疗的患者达到EASI50的比例更高（64.7％）。在第12周的继发性和探索性终点研究中，与安慰剂相比，数值有所改善，在第16周时进一步改善。各治疗组之间出现的紧急治疗不良事件相似。

局限性

接受安慰剂治疗的患者的应答率高于预期，可能归因于TCS。

结论

尽管在统计学上不显着，但在第12周的所有终点上均显示出优于安慰剂的数值改善，第16周的响应更大。