Siegels Doreen, Heratizadeh Annice, Abraham Susanne, Binnmyr Jonas, Brockow Knut, Irvine Alan D, Halken Susanne, Mortz Charlotte G, Flohr Carsten, Schmid-Grendelmeier Peter, Van der Poel Lauri-Ann, Muraro Antonella, Weidinger Stephan, Werfel Thomas, Schmitt Jochen
Center for Evidence-Based Healthcare, University Hospital Dresden, Dresden, Germany.
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy Hannover Medical School, Hannover, Germany.
Allergy. 2021 Apr;76(4):1053-1076. doi: 10.1111/all.14631. Epub 2020 Nov 4.
As an evidence resource for the currently planned European Academy of Allergy and Clinical Immunology (EAACI) clinical practice guideline "systemic treatment of atopic dermatitis (AD)," we critically appraised evidence on systemic treatments for moderate-to-severe AD.
We systematically identified randomized controlled trials (RCTs) investigating the safety and efficacy of systemic treatments for AD up to February 2020. Primary efficacy outcomes were clinical signs, AD symptoms and health-related quality of life. Primary safety outcomes included cumulative incidence rates for (serious) adverse events. Trial quality was assessed applying the Cochrane Risk of Bias Tool 2.0. Meta-analyses were conducted where appropriate.
50 RCTs totalling 6681 patients were included. Trial evidence was identified for apremilast, azathioprine (AZA), baricitinib, ciclosporin A (CSA), corticosteroids, dupilumab, interferon-gamma, intravenous immunoglobulins (IVIG), mepolizumab, methotrexate (MTX), omalizumab, upadacitinib and ustekinumab. Meta-analyses were indicated for the efficacy of baricitinib [EASI75 RD 0.16, 95% CI (0.10;0.23)] and dupilumab [EASI75, RD 0.37, 95% CI (0.32;0.42)] indicating short-term (ie 16-week treatment) superiority over placebo. Furthermore, efficacy analyses of AZA and CSA indicated short-term superiority over placebo; however, nonvalidated scores were used and can therefore not be compared to EASI.
The most robust, replicated high-quality trial evidence is present for the efficacy and safety of dupilumab for up to 1 year in adults. Robust trial evidence was further revealed for AZA, baricitinib and CSA. Methodological restrictions led to limited evidence-based conclusions for all other systemic treatments. Head-to-head trials with novel systemic treatments are required to clarify the future role of conventional therapies.
作为当前计划制定的欧洲变态反应与临床免疫学会（EAACI）关于“特应性皮炎（AD）的系统治疗”临床实践指南的证据资源，我们对中度至重度AD系统治疗的证据进行了严格评估。
我们系统检索了截至2020年2月调查AD系统治疗安全性和有效性的随机对照试验（RCT）。主要疗效结局为临床体征、AD症状及健康相关生活质量。主要安全性结局包括（严重）不良事件的累积发生率。采用Cochrane偏倚风险工具2.0评估试验质量。在适当情况下进行荟萃分析。
纳入了共6681例患者的50项RCT。确定了关于阿普米拉斯、硫唑嘌呤（AZA）、巴瑞替尼、环孢素A（CSA）、皮质类固醇、度普利尤单抗、干扰素-γ、静脉注射免疫球蛋白（IVIG）、美泊利单抗、甲氨蝶呤（MTX）、奥马珠单抗、乌帕替尼和乌司奴单抗的试验证据。对巴瑞替尼[湿疹面积和严重程度指数（EASI）改善75%，风险差值（RD）0.16，95%置信区间（CI）（0.10；0.23）]和度普利尤单抗[EASI改善75%，RD 0.37，95%CI（0.32；0.42）]的疗效进行了荟萃分析，表明在短期（即16周治疗）内优于安慰剂。此外，AZA和CSA的疗效分析表明短期优于安慰剂；然而，使用的是未经验证的评分，因此无法与EASI进行比较。
度普利尤单抗在成人中长达1年的疗效和安全性有最有力、可重复的高质量试验证据。AZA、巴瑞替尼和CSA也有有力的试验证据。方法学限制导致所有其他系统治疗基于证据的结论有限。需要开展新型系统治疗的头对头试验以明确传统疗法的未来作用。
