Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial
Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial
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DOI：
10.1016/j.cgh.2021.04.022
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发表时间：
2022-03-01
影响因子：
12.6
通讯作者：
Dellon, Evan S.
中科院分区：
文献类型：
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作者：
Hirano, Ikuo;Collins, Margaret H.;Dellon, Evan S.
背景与目的：嗜酸性粒细胞性食管炎（EoE）是一种慢性免疫介导性疾病，目前尚未获得美国食品和药物管理局批准的药物治疗。方法：在这项双盲，安慰剂对照，3期试验中，11-55岁的EoE和吞咽困难患者被随机分为2:1，在学术或社区护理实践中接受布地奈德口服混悬液（BOS） 2.0 mg，每日两次或安慰剂，为期12周。共同主要终点是12周内严格组织学反应者的比例（吞咽困难症状问卷[DSQ]评分降低= 30%）。从基线到第12周，DSQ评分（主要次要终点）和EoE内镜参考评分（EREFS）（次要终点）的变化，并检查安全性参数。结果：总体而言，318例患者（BOS, n = 213；安慰剂，n = 105）被随机分组，接受>= 1剂量的研究治疗。接受bos治疗的患者比接受安慰剂治疗的患者获得严格的组织学反应(53.1% vs 1.0%； δ值为52%[95%可信区间（CI）， 43.3%-59.1%]；P < 0.001)或症状反应（52.6% vs 39.1%； δ值为13% [95% CI， 1.6%-24.3%]; P = 0.024）。在12周内，bos治疗的患者在最小二乘平均DSQ评分和EREFS方面也比安慰剂治疗的患者有更大的改善：DSQ， -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Delta-3.9 [95% CI, -7.1至-0.8];P = 0.015)；EREFS -4.0 0.3 (SEM) -2.2 vs 0.4 (SEM)(δ- 1.8 (95% CI, -2.6 - -1.1); P <措施)。BOS耐受良好；大多数不良事件的严重程度为轻度或中度。结论：在EoE患者中，BOS 2.0 mg每日2次在改善组织学、症状和内窥镜预后方面优于安慰剂，持续12周。bos2.0 mg每日两次耐受性良好。
BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease for which there is currently no pharmacologic therapy approved by the US Food and Drug Administration.METHODS: In this double-blind, placebo-controlled, phase 3 trial, patients 11-55 years of age with EoE and dysphagia were randomized 2:1 to receive budesonide oral suspension (BOS) 2.0 mg twice daily or placebo for 12 weeks at academic or community care practices. Co-primary endpoints were the proportion of stringent histologic responders (= 30 % reduction in Dysphagia Symptom Questionnaire [DSQ] score) over 12 weeks. Changes in DSQ score (key secondary endpoint) and EoE Endoscopic Reference Score (EREFS) (secondary endpoint) from baseline to week 12, and safety parameters were examined.RESULTS: Overall, 318 patients (BOS, n = 213; placebo, n = 105) were randomized and received >= 1 dose of study treatment. More BOS-treated than placebo-treated patients achieved a stringent histologic response (53.1% vs 1.0%; Delta 52% [95% confidence interval (CI), 43.3%-59.1%]; P < .001) or symptom response (52.6% vs 39.1%; Delta 13% [95% CI, 1.6%-24.3%]; P = .024) over 12 weeks. BOS-treated patients also had greater improvements in least-squares mean DSQ scores and EREFS over 12 weeks than placebo-treated patients: DSQ, -13.0 (SEM 1.2) vs -9.1 (SEM 1.5) (Delta-3.9 [95% CI, -7.1 to -0.8]; P = .015); EREFS, -4.0 (SEM 0.3) vs -2.2 (SEM 0.4) (Delta-1.8 [95% CI, -2.6 to -1.1]; P < .001). BOS was well tolerated; most adverse events were mild or moderate in severity.CONCLUSIONS: In patients with EoE, BOS 2.0 mg twice daily was superior to placebo in improving histologic, symptomatic, and endoscopic outcomes over 12 weeks. BOS 2.0 mg twice daily was well tolerated.