Gutermuth J, Pink A E, Worm M, Soldbro L, Bjerregård Øland C, Weidinger S
Department of Dermatology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
St John's Institute of Dermatology, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Br J Dermatol. 2022 Mar;186(3):440-452. doi: 10.1111/bjd.20832. Epub 2021 Dec 22.
Patients with severe atopic dermatitis (AD) not controlled with topical therapy have limited treatment options. Ciclosporin A (CSA) is a commonly used, broad immunosuppressant in AD, but treatment with CSA requires monitoring for potentially serious adverse effects. In a previous phase III trial, tralokinumab plus topical corticosteroids (TCS) as needed provided early and sustained improvements in AD signs and symptoms.
To evaluate the efficacy and safety of tralokinumab plus TCS in adult patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.
In this 26-week, multicentre, parallel, randomized, double-blind, placebo-controlled, phase III trial, European adults with severe AD were randomized 1 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks plus TCS as needed. The primary endpoint was a 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16.
In total, 277 patients were randomized. At week 16, more patients treated with tralokinumab plus TCS vs. placebo plus TCS achieved EASI 75 [64·2% vs. 50·5%; difference 14·1% (95% confidence interval 2·5-25·7); P = 0·018], which increased further up to week 26. Improvements in AD severity were accompanied by early improvements in patient-reported outcomes, including Dermatology Life Quality Index, Patient-Oriented Eczema Measure, pruritus and sleep interference. Tralokinumab plus TCS also showed a higher EASI75 response at week 16 among patients who had previously failed CSA therapy vs. placebo plus TCS (57% vs. 41%). The overall incidence of adverse events was similar between treatment arms.
Tralokinumab 300 mg plus TCS as needed was effective and well tolerated in patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.
严重特应性皮炎（AD）患者若局部治疗无法控制病情，则治疗选择有限。环孢素A（CSA）是AD中常用的一种广泛的免疫抑制剂，但使用CSA治疗需要监测潜在的严重不良反应。在之前的一项III期试验中，按需使用曲罗芦单抗加外用糖皮质激素（TCS）可使AD的体征和症状得到早期且持续的改善。
评估曲罗芦单抗加TCS在疾病未得到CSA充分控制或对口服CSA有禁忌证的重度AD成年患者中的疗效和安全性。
在这项为期26周的多中心、平行、随机、双盲、安慰剂对照III期试验中，将患有重度AD的欧洲成年人按1∶1随机分为皮下注射曲罗芦单抗300mg组或安慰剂组，每2周一次，按需加用TCS。主要终点是第16周时湿疹面积和严重程度指数（EASI）改善75%（EASI 75）。
总共277例患者被随机分组。在第16周时，与安慰剂加TCS相比，更多接受曲罗芦单抗加TCS治疗的患者实现了EASI 75[64.2%对50.5%；差异14.1%（95%置信区间2.5 - 25.7）；P = 0.018]，到第26周时进一步增加。AD严重程度的改善伴随着患者报告结局的早期改善，包括皮肤病生活质量指数、以患者为导向的湿疹测量、瘙痒和睡眠干扰。在之前CSA治疗失败的患者中，与安慰剂加TCS相比，曲罗芦单抗加TCS在第16周时也显示出更高的EASI75反应率（57%对41%）。各治疗组不良事件的总体发生率相似。
按需使用300mg曲罗芦单抗加TCS对疾病未得到CSA充分控制或对口服CSA有禁忌证的重度AD患者有效且耐受性良好。
