Supplementary Material for: Histologic and Clinical Effects of Different Topical Corticosteroids for Eosinophilic Esophagitis: Lessons from an Updated Meta-Analysis of Placebo-Controlled Randomized Trials

<b><i>Background:</i></b> Topical corticosteroids (TS) have become standard therapy for eosinophilic esophagitis (EoE). However, a variety of drug formulations have been used for which results of histological and clinical responses may be different. We aimed at determining the short-term histologic efficacy of TS for EoE based on randomized placebo-controlled trials and to review clinical response. <b><i>Methods:</i></b> We searched MEDLINE, ISI Web of Science, and clinicaltrials.gov for randomized controlled trials (RCTs) on TS versus placebo for active EoE published until June 2019. Treatment effects were calculated as risk ratios (RRs) comparing histologic remission between groups. <b><i>Results:</i></b> Nine RCTs (6 budesonide and 3 fluticasone) involving a total of 483 participants were included. A substantial overall effect of TS on acute histologic remission (RR 12.5, 95% confidence interval 6.0–25.9) was found despite varying definitions of histologic response. Indirect comparisons between drug and formulation types showed a trend for a better histologic efficacy of budesonide (RR 13.5 vs. 10.4 fluticasone) and for the orodispersible tablet (RR 46.2 vs. 11.5 suspension, and 10.4 nebulized formula/spray), but only based on small patient numbers. Scores used for clinical response assessment were different between studies, and short-term clinical results were less impressive: significant differences favoring TS were found in 4/9 RCTs (4/6 budesonide, 0/3 fluticasone). <b><i>Conclusions:</i></b> TS are effective for short-term induction of histological remission in EoE with less impressive clinical response rates. The mode of drug delivery to the esophagus may be a relevant factor for the degree of histologic remission. Further trials should use uniform assessment criteria and long-term patient-centered outcomes.

<b><i>背景：</i></b> 局部糖皮质激素（Topical corticosteroids, TS）已成为嗜酸性粒细胞性食管炎（eosinophilic esophagitis, EoE）的标准治疗方案。然而，临床已应用多种药物剂型，不同剂型的组织学与临床应答效果或存在差异。本研究旨在基于截至2019年6月发表的随机安慰剂对照试验，明确局部糖皮质激素治疗嗜酸性粒细胞性食管炎的短期组织学疗效，并综述其临床应答情况。<b><i>方法：</i></b> 我们检索了MEDLINE、ISI Web of Science及clinicaltrials.gov数据库，收集截至2019年6月发表的、针对活动性嗜酸性粒细胞性食管炎比较局部糖皮质激素与安慰剂的随机对照试验（randomized controlled trials, RCTs）。以风险比（risk ratios, RRs）作为组间组织学缓解的比较指标，计算治疗效应。<b><i>结果：</i></b> 本研究共纳入9项随机对照试验（其中6项针对布地奈德（budesonide）、3项针对氟替卡松（fluticasone）），共计483名受试者。尽管不同研究对组织学应答的定义存在差异，但结果显示局部糖皮质激素对急性组织学缓解具有显著的整体效应（风险比=12.5，95%置信区间6.0~25.9）。不同药物及剂型的间接比较显示，布地奈德的组织学疗效呈优于氟替卡松的趋势（风险比分别为13.5与10.4）；口腔崩解片剂型的疗效亦呈优于混悬剂（风险比分别为46.2与11.5）及雾化制剂/喷雾（风险比10.4）的趋势，但上述结论均基于较小的受试者样本量。不同研究采用的临床应答评估量表存在差异，短期临床疗效则相对欠佳：9项试验中有4项（6项布地奈德相关试验中4项、3项氟替卡松相关试验中0项）显示局部糖皮质激素具有显著优势。<b><i>结论：</i></b> 局部糖皮质激素可有效诱导嗜酸性粒细胞性食管炎的短期组织学缓解，但临床应答率相对较低。药物经食管递送的方式或为影响组织学缓解程度的相关因素。未来的试验应采用统一的评估标准，并关注以患者为中心的长期结局指标。