Tralokinumab Efficacy and Safety, with or without Topical Corticosteroids, in North American Adults with Moderate-to-Severe Atopic Dermatitis: A Subanalysis of Phase 3 Trials ECZTRA 1, 2, and 3,Dermatology and Therapy

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Tralokinumab Efficacy and Safety, with or without Topical Corticosteroids, in North American Adults with Moderate-to-Severe Atopic Dermatitis: A Subanalysis of Phase 3 Trials ECZTRA 1, 2, and 3
Dermatology and Therapy ( IF 3.5 ) Pub Date : 2022-09-24 , DOI: 10.1007/s13555-022-00805-y
Andrew Blauvelt ₁ , Melinda Gooderham ₂ , Neal Bhatia ₃ , Richard G Langley ₄ , Shannon Schneider ₅ , John Zoidis ₅ , Azra Kurbasic ₆ , April Armstrong ₇ , Jonathan I Silverberg ₈

Affiliation

Introduction

In pivotal phase 3 tralokinumab monotherapy (ECZTRA 1/2) and topical corticosteroid (TCS) combination (ECZTRA 3) trials in adults with moderate-to-severe atopic dermatitis (AD), tralokinumab significantly improved signs and symptoms of AD. Geographic region may impact treatment response due to potential differences in race and ethnicity, and based on findings in other therapy areas. Here, we evaluated the efficacy and safety of tralokinumab in the ECZTRA 1/2/3 North American population at week 16, as well as maintenance of responses over time, and compared these data side-by-side with those of the ECZTRA 1/2/3 non-North American population.

Methods

Primary endpoints were Investigator’s Global Assessment score of 0 or 1 (IGA 0/1; clear or almost clear) or at least 75% improvement in Eczema Area and Severity Index (EASI-75) at week 16. At week 16, tralokinumab-treated IGA 0/1 or EASI-75 responders were re-randomized 2:2:1 to tralokinumab 300 mg q2w, or q4w, or placebo (ECZTRA 1/2) and 1:1 to tralokinumab 300 mg q2w or q4w (ECZTRA 3).

Results

Overall, 559/1596 (35%) and 160/380 (42.1%) patients randomized in ECZTRA 1/2 and ECZTRA 3 were from North America, respectively. At week 16, IGA 0/1 and EASI-75 response rates were greater with tralokinumab versus placebo in ECZTRA 1/2 (IGA 0/1: 25.3% vs 15.1%; 95% confidence interval [CI] 3.0, 17.3; p = 0.012; EASI-75, 40.1% vs 19.4%; 95% CI 12.6, 28.7; p < 0.001) and ECZTRA 3 (IGA 0/1, 40.0% vs 25.9%; 95% CI − 0.5, 28.3; p = 0.074; EASI-75: 58.1% vs 37.0%; 95% CI 4.9, 37.0; p = 0.012) and tralokinumab was well tolerated in the North American population. Patients with IGA 0/1 or EASI-75 response at week 16 demonstrated sustained responses at week 52 and week 32 in ECZTRA 1/2 and ECZTRA 3, respectively. Similar findings were observed in the non-North American trial populations.

Conclusions

Tralokinumab, with or without TCS, displayed similar efficacy and safety in patients with moderate-to-severe AD across the North American population, and was comparable to the non-North American population.

Clinical Trial Registration

NCT03131648 (registered 27-Apr-2017); NCT03160885 (registered 19-May-2017); NCT03363854 (registered 6-Dec-2017).

中文翻译：

Tralokinumab 的疗效和安全性，无论是否使用局部皮质类固醇，在北美成人中度至重度特应性皮炎：3 期试验 ECZTRA 1、2 和 3 的亚分析

介绍

在中度至重度特应性皮炎 (AD) 成人的关键 3 期 tralokinumab 单药治疗 (ECZTRA 1/2) 和局部皮质类固醇 (TCS) 联合 (ECZTRA 3) 试验中，tralokinumab 显着改善了 AD 的体征和症状。由于种族和民族的潜在差异，以及基于其他治疗领域的发现，地理区域可能会影响治疗反应。在这里，我们在第 16 周评估了 tralokinumab 在 ECZTRA 1/2/3 北美人群中的疗效和安全性，以及随着时间的推移维持反应，并将这些数据与 ECZTRA 1/ 的数据并排比较2/3 非北美人口。

方法

主要终点是 0 或 1 的调查员全球评估评分（IGA 0/1；清除或几乎清除）或在第 16 周时湿疹面积和严重程度指数 (EASI-75) 至少改善 75%。在第 16 周，tralokinumab 治疗IGA 0/1 或 EASI-75 应答者以 2:2:1 重新随机分配至 tralokinumab 300 mg q2w 或 q4w 或安慰剂 (ECZTRA 1/2) 和 1:1 至 tralokinumab 300 mg q2w 或 q4w (ECZTRA 3) .

结果

总体而言，在 ECZTRA 1/2 和 ECZTRA 3 中随机分配的 559/1596 (35%) 和 160/380 (42.1%) 名患者分别来自北美。在第 16 周，在 ECZTRA 1/2 中，tralokinumab 与安慰剂相比，IGA 0/1 和 EASI-75 反应率更高（IGA 0/1：25.3% 对 15.1%；95% 置信区间 [CI] 3.0, 17.3； p = 0.012；EASI-75, 40.1% vs 19.4%；95% CI 12.6, 28.7； p < 0.001) 和 ECZTRA 3 (IGA 0/1, 40.0% vs 25.9%; 95% CI - 0.5, 28.3; p = 0.074; EASI-75：58.1% 对 37.0%；95% CI 4.9, 37.0； p = 0.012) 并且曲洛金单抗在北美人群中具有良好的耐受性。在第 16 周有 IGA 0/1 或 EASI-75 反应的患者分别在 ECZTRA 1/2 和 ECZTRA 3 的第 52 周和第 32 周表现出持续反应。在非北美试验人群中也观察到了类似的结果。