Department of Paediatric Dermatology, St John's Institute of Dermatology, King's College London and Guy's and St Thomas' NHS Foundation Trust, London, UK.
Liverpool Clinical Trials Centre, University of Liverpool, Liverpool, UK.
Br J Dermatol. 2023 Nov 16;189(6):674-684. doi: 10.1093/bjd/ljad281.
Conventional systemic drugs are used to treat children and young people (CYP) with severe atopic dermatitis (AD) worldwide, but no robust randomized controlled trial (RCT) evidence exists regarding their efficacy and safety in this population. While novel therapies have expanded therapeutic options, their high cost means traditional agents remain important, especially in lower-resource settings.
To compare the safety and efficacy of ciclosporin (CyA) with methotrexate (MTX) in CYP with severe AD in the TREatment of severe Atopic Eczema Trial (TREAT) trial.
We conducted a parallel group assessor-blinded RCT in 13 UK and Irish centres. Eligible participants aged 2-16 years and unresponsive to potent topical treatment were randomized to either oral CyA (4 mg kg-1 daily) or MTX (0.4 mg kg-1 weekly) for 36 weeks and followed-up for 24 weeks. Co-primary outcomes were change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare (relapse) after treatment cessation. Secondary outcomes included change in quality of life (QoL) from baseline to 60 weeks; number of participant-reported flares following treatment cessation; proportion of participants achieving ≥ 50% improvement in Eczema Area and Severity Index (EASI 50) and ≥ 75% improvement in EASI (EASI 75); and stratification of outcomes by filaggrin status.
In total, 103 participants were randomized (May 2016-February 2019): 52 to CyA and 51 to MTX. CyA showed greater improvement in disease severity by 12 weeks [mean difference in o-SCORAD -5.69, 97.5% confidence interval (CI) -10.81 to -0.57 (P = 0.01)]. More participants achieved ≥ 50% improvement in o-SCORAD (o-SCORAD 50) at 12 weeks in the CyA arm vs. the MTX arm [odds ratio (OR) 2.60, 95% CI 1.23-5.49; P = 0.01]. By 60 weeks MTX was superior (OR 0.33, 95% CI 0.13-0.85; P = 0.02), a trend also seen for ≥ 75% improvement in o-SCORAD (o-SCORAD 75), EASI 50 and EASI 75. Participant-reported flares post-treatment were higher in the CyA arm (OR 3.22, 95% CI 0.42-6.01; P = 0.02). QoL improved with both treatments and was sustained after treatment cessation. Filaggrin status did not affect outcomes. The frequency of adverse events (AEs) was comparable between both treatments. Five (10%) participants on CyA and seven (14%) on MTX experienced a serious AE.
Both CyA and MTX proved effective in CYP with severe AD over 36 weeks. Participants who received CyA showed a more rapid response to treatment, while MTX induced more sustained disease control after discontinuation.
在全球范围内，传统的全身用药物被用于治疗患有严重特应性皮炎（AD）的儿童和青少年（CYP），但在该人群中，关于这些药物的疗效和安全性的稳健随机对照试验（RCT）证据并不存在。虽然新型疗法扩大了治疗选择，但由于其成本高昂，传统药物仍然很重要，尤其是在资源较少的环境中。
在 TREatment of severe Atopic Eczema Trial（TREAT）试验中比较环孢素（CyA）和甲氨蝶呤（MTX）在 CYP 中治疗严重 AD 的安全性和疗效。
我们在英国和爱尔兰的 13 个中心进行了一项平行组评估者盲法 RCT。符合条件的参与者年龄在 2-16 岁之间，对强效局部治疗无反应，随机分为口服 CyA（4mg/kg 每日）或 MTX（0.4mg/kg 每周）治疗 36 周，并随访 24 周。主要结局是从基线到 12 周时客观严重度评分的特应性皮炎（o-SCORAD）的变化和治疗停止后首次显著复发（复发）的时间。次要结局包括从基线到 60 周时生活质量（QoL）的变化；治疗停止后参与者报告的复发次数；达到 Eczema Area and Severity Index（EASI 50）改善≥50%和 EASI 改善≥75%的参与者比例；以及根据丝聚蛋白状态分层的结局。
共有 103 名参与者被随机分配（2016 年 5 月至 2019 年 2 月）：52 名接受 CyA，51 名接受 MTX。CyA 在 12 周时显示出更大的疾病严重程度改善[o-SCORAD 的平均差值为-5.69，97.5%置信区间（CI）为-10.81 至-0.57（P=0.01）]。在 12 周时，CyA 组达到 o-SCORAD 改善≥50%的参与者比例高于 MTX 组[优势比（OR）为 2.60，95%CI 为 1.23-5.49；P=0.01]。到 60 周时，MTX 更具优势（OR 为 0.33，95%CI 为 0.13-0.85；P=0.02），o-SCORAD 改善≥75%（o-SCORAD 75）、EASI 50 和 EASI 75 也出现了同样的趋势。在 CyA 组中，治疗后报告的复发次数更高（OR 为 3.22，95%CI 为 0.42-6.01；P=0.02）。两种治疗方法均改善了 QoL，且在治疗停止后持续改善。丝聚蛋白状态对结局没有影响。两种治疗方法的不良事件（AE）发生率相似。5（10%）名接受 CyA 的参与者和 7（14%）名接受 MTX 的参与者发生了严重 AE。
CyA 和 MTX 在 CYP 中治疗严重 AD 均在 36 周内有效。接受 CyA 的参与者表现出更快的治疗反应，而 MTX 在停药后诱导更持续的疾病控制。
