Section of Pediatric Gastroenterology, Hepatology and Nutrition, Indiana University School of Medicine, Riley Hospital for Children at Indiana University Health, Indianapolis, Indiana.
Meritage Pharma, Inc, San Diego, California.
Clin Gastroenterol Hepatol. 2015 Jan;13(1):66-76.e3. doi: 10.1016/j.cgh.2014.05.021. Epub 2014 Jun 4.
BACKGROUND & AIMS: No treatment has been approved by the U.S. Food and Drug Administration for eosinophilic esophagitis (EoE). We investigated the efficacy and safety of a new formulation of oral budesonide suspension (OBS), a corticosteroid, in a prospective, placebo-controlled, dose-ranging study.
Subjects 2-18 years old with symptoms of EoE and peak eosinophil counts ≥20/high-power field at ≥2 levels of the esophagus were randomly assigned to groups given placebo or low-dose, medium-dose, or high-dose OBS for 12 weeks. Doses and volumes were adjusted on the basis of patients' age to cover the entire esophagus. The primary efficacy end point was compound response to therapy (peak eosinophil counts ≤6/high-power field at all levels of the esophagus and ≥50% reduction in EoE symptom score). Multiple safety parameters were evaluated.
Data from 71 subjects who completed all efficacy assessments were included in the primary efficacy analysis. At the end of 12 weeks, there were significantly greater percentages of responders in groups given medium-dose OBS (52.6%, P = .0092) and high-dose OBS (47.1%, P = .0174) than in the group given placebo (5.6%); there was no significant difference in percentages of responders between the low-dose OBS (11.8%) and placebo groups (P = .5282). The significant compound responses noted in the medium-dose and high-dose OBS groups were accounted for by the significant histologic responses; in contrast, all 4 groups (including the placebo group) had large symptom responses, and there was no significant difference in the percentage of subjects with a symptom response in either OBS group compared with the placebo group (P ≥ .1235). There were no unexpected safety concerns or signals.
Peak eosinophil counts were significantly reduced throughout the esophagus in pediatric patients with EoE who were given medium-dose and high-dose OBS. There was a large symptom response to placebo that was similar to symptom responses in the OBS groups; symptom response did not distinguish OBS from placebo. ClinicalTrials.gov number, NCT00762073.
目前尚无获美国食品和药物管理局批准用于治疗嗜酸性食管炎（EoE）的方法。我们研究了一种新的布地奈德混悬液（OBS）口服制剂（一种皮质类固醇）在一项前瞻性、安慰剂对照、剂量范围研究中的疗效和安全性。
纳入年龄为 2-18 岁、具有 EoE 症状且食管上 2 个或以上水平的嗜酸性粒细胞计数峰值≥20/高倍视野的患者，随机分为安慰剂组或低剂量、中剂量或高剂量 OBS 组，治疗 12 周。根据患者年龄调整剂量和容量，以覆盖整个食管。主要疗效终点为治疗复合应答（所有食管水平的嗜酸性粒细胞计数峰值≤6/高倍视野且 EoE 症状评分降低≥50%）。评估了多种安全性参数。
71 例完成所有疗效评估的患者的数据纳入主要疗效分析。治疗 12 周后，中剂量 OBS 组（52.6%，P =.0092）和高剂量 OBS 组（47.1%，P =.0174）的应答者比例明显高于安慰剂组（5.6%）；低剂量 OBS 组（11.8%）与安慰剂组之间的应答者比例无显著差异（P =.5282）。中剂量和高剂量 OBS 组的显著复合应答归因于显著的组织学应答；相比之下，所有 4 组（包括安慰剂组）均具有较大的症状应答，且 OBS 组与安慰剂组之间的症状应答者比例无显著差异（P ≥.1235）。未发现意外的安全性问题或信号。
在接受中剂量和高剂量 OBS 治疗的儿童 EoE 患者中，整个食管的嗜酸性粒细胞计数峰值显著降低。安慰剂组的症状应答较大，与 OBS 组的症状应答相似；症状应答不能区分 OBS 与安慰剂。临床试验注册号：NCT00762073。
