BACKGROUND Atopic dermatitis (AD) has a variable disease course and intermittent triggers, and responses to topical therapy vary, potentially affecting the magnitude of the placebo response in AD trials. OBJECTIVE To determine the predictors of increased placebo response in randomized controlled trials of AD. METHODS We performed a systematic review and meta-analysis of randomized controlled trials for systemic therapy in AD published during 2007-2018. We searched the Cochrane Library, Medline, Embase, Global Resource for EczemA Trials (GREAT), Literature of the Latin American and Caribbean Health Sciences (LILACS), and Scopus. Two authors performed study selection and data extraction. Multivariable mixed models were constructed for Cohen D of Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), numeric rating scale (NRS)-itch and visual analog scale (VAS)-itch, and Dermatology Life Quality Index (DLQI). RESULTS Overall, 64 trials were included. Use of concomitant topical therapy prescriptions, study duration ≥3 months, and fewer treatment arms were associated with an increased placebo response for EASI, NRS- and VAS-itch, and DLQI. For EASI, the placebo response was increased in studies with a higher proportion of male patients, mild-moderate mean baseline EASI scores, and no blinding. For NRS-itch, and VRS-itch, higher placebo responses were associated with higher proportions of male patients and moderate-severe mean itch scores at baseline. CONCLUSION Placebo responses can be reduced in clinical trials of systemic therapy in AD by incorporating double- and triple-blinding, balancing the sex distribution of patients, disallowing concomitant use of prescription topical therapy, and having shorter study durations.

中文翻译：

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异位性皮炎全身治疗的随机对照试验中的安慰剂反应：系统评价和荟萃分析。

背景技术特应性皮炎（AD）具有可变的病程和间歇性触发因素，并且对局部治疗的反应各不相同，从而可能影响AD试验中安慰剂反应的程度。目的确定AD随机对照试验中安慰剂反应增加的预测因素。方法我们对2007-2018年发表的AD系统治疗的随机对照试验进行了系统回顾和荟萃分析。我们搜索了Cochrane图书馆，Medline，Embase，EczemA试验的全球资源（GREAT），拉丁美洲和加勒比健康科学文献（LILACS）和Scopus。两位作者进行了研究选择和数据提取。针对湿疹面积和严重程度指数（EASI），SCOR特应性皮炎（SCORAD），数字评分量表（NRS）痒和视觉模拟量表（VAS）痒，以及皮肤病生活质量指数（DLQI）。结果总的来说，包括64个试验。使用伴随的局部治疗处方，研究持续时间≥3个月以及更少的治疗组与EASI，NRS和VAS瘙痒以及DLQI的安慰剂反应增加相关。对于EASI，在男性患者比例较高，基线EASI分数为轻度至中度且无致盲的研究中，安慰剂反应有所增加。对于NRS瘙痒和VRS瘙痒，较高的安慰剂反应与男性患者比例较高和基线时中度至重度平均瘙痒评分相关。结论在AD全身治疗的临床试验中，可以通过掺入双盲和三盲，平衡患者的性别分布来减少安慰剂反应，