Department of Dermatology, Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands.
Department of Dermatology, Erasmus Medical Centre, Erasmus University Rotterdam, Rotterdam, the Netherlands.
Br J Dermatol. 2018 Jun;178(6):1288-1296. doi: 10.1111/bjd.16240. Epub 2018 Apr 10.
Systemic treatment is indicated for moderate-to-severe atopic dermatitis (AD) refractory to topical treatment. Long-term evidence, up to 5 years, of off-label prescribed methotrexate (MTX) and azathioprine (AZA) is lacking.
To investigate long-term effectiveness, safety and drug survival of MTX and AZA.
In an open-label follow-up phase of a clinical trial, patients were seen every 3 months for 5 years. MTX and AZA doses could be increased or decreased concurrent with daily clinical practice. Primary effectiveness outcomes were mean absolute and relative reduction in SCORing Atopic Dermatitis (SCORAD) index and Investigator's Global Assessment (IGA) after 5 years compared with baseline. To assess safety, the type, frequency, severity and relatedness to treatment of adverse events were investigated. Drug survival was analysed by Kaplan-Meier curves.
Thirty-five of 43 originally included patients participated, of whom 27 completed the follow-up. At year 5, the mean relative reduction in SCORAD index was similar in the MTX and AZA groups: 53% and 54% using descriptive analysis. Twelve serious adverse events occurred in 5 years; for three there was a possible causal relationship. Drug survival demonstrated a longer survival for MTX, but survival in both groups was low after 5 years (MTXn = 5, AZAn = 1).
Based on this relatively small pragmatic study, MTX and AZA seem to be effective and safe as maintenance treatments in moderate-to-severe AD up to 5 years. Few patients in both groups survive on their originally allocated drug although some discontinued because of controlled AD.
对于外用治疗无效的中重度特应性皮炎（AD），需要进行系统治疗。缺乏关于甲氨蝶呤（MTX）和硫唑嘌呤（AZA）的 5 年以上的长期非适应证处方使用证据。
研究 MTX 和 AZA 的长期疗效、安全性和药物存续率。
在一项临床试验的开放性随访阶段，患者每 3 个月随访一次，随访 5 年。可根据日常临床实践增加或减少 MTX 和 AZA 的剂量。主要疗效结局为与基线相比，5 年后 SCORing 特应性皮炎（SCORAD）指数和研究者整体评估（IGA）的平均绝对和相对降低。为了评估安全性，研究了不良事件的类型、频率、严重程度以及与治疗的相关性。通过 Kaplan-Meier 曲线分析药物存续率。
43 名最初纳入的患者中有 35 名参加了随访，其中 27 名完成了随访。5 年后，MTX 和 AZA 组的 SCORAD 指数相对降低的平均值相似：描述性分析分别为 53%和 54%。5 年内发生了 12 例严重不良事件；其中 3 例可能与治疗有关。药物存续率表明 MTX 的存续时间更长，但 5 年后两组的药物存续率都较低（MTXn = 5，AZAn = 1）。
基于这项相对较小的实用研究，MTX 和 AZA 似乎可作为中重度 AD 的维持治疗，在 5 年内有效且安全。尽管有些患者因 AD 得到控制而停药，但两组患者中很少有患者能继续使用最初分配的药物。
