Department of Gastroenterology, Hospital General de Tomelloso, Tomelloso, Spain; Centro de Investigación Biomédica en Red en Enfermedades Hepáticas y Digestivas, Spain.
Center for Digestive Diseases, Internal Medicine Center Eppendorf, Hamburg, Germany; Center for Esophageal Diseases, University Hospital Hamburg-Eppendorf, Germany.
Gastroenterology. 2019 Jul;157(1):74-86.e15. doi: 10.1053/j.gastro.2019.03.025. Epub 2019 Mar 26.
BACKGROUND & AIMS: Swallowed topical-acting corticosteroids are recommended as first-line therapy for eosinophilic esophagitis (EoE). Asthma medications not optimized for esophageal delivery are sometimes effective, although given off-label. We performed a randomized, placebo-controlled trial to assess the effectiveness and tolerability of a budesonide orodispersible tablet (BOT), which allows the drug to be delivered to the esophagus in adults with active EoE.
We performed a double-blind, parallel study of 88 adults with active EoE in Europe. Patients were randomly assigned to groups that received BOT (1 mg twice daily; n = 59) or placebo (n = 29) for 6 weeks. The primary end point was complete remission, based on clinical and histologic factors, including dysphagia and odynophagia severity ≤2 on a scale of 0-10 on each of the 7 days before the end of the double-blind phase and a peak eosinophil count <5 eosinophils/high power field. Patients who did not achieve complete remission at the end of the 6-week double-blind phase were offered 6 weeks of open-label treatment with BOT (1 mg twice daily).
At 6 weeks, 58% of patients given BOT were in complete remission compared with no patients given placebo (P < .0001). The secondary end point of histologic remission was achieved by 93% of patients given BOT vs no patients given placebo (P < .0001). After 12 weeks, 85% of patients had achieved remission. Six-week and 12-week BOT administration were safe and well tolerated; 5% of patients who received BOT developed symptomatic, mild candida, which was easily treated with an oral antifungal agent.
In a randomized trial of adults with active EoE, we found that budesonide oral tablets were significantly more effective than placebo in inducing clinical and histologic remission. Eudra-CT number 2014-001485-99; ClinicalTrials.gov ID NCT02434029.
对于嗜酸性食管炎（EoE），推荐使用口服局部作用的皮质类固醇作为一线治疗药物。虽然为超适应证用药，但有时经优化用于食管输送的哮喘药物也具有一定疗效。我们开展了一项随机、安慰剂对照试验，以评估布地奈德口腔崩解片（BOT）在活动期 EoE 成人患者中的有效性和耐受性，这种药物可将药物递送至食管。
我们在欧洲开展了一项针对 88 例活动期 EoE 成人患者的双盲、平行研究。患者被随机分为两组，分别接受 BOT（1 毫克，每日 2 次；n=59）或安慰剂（n=29）治疗 6 周。主要终点是基于临床和组织学因素的完全缓解，包括在双盲阶段结束前的 7 天内，每天的吞咽困难和咽喉痛严重程度评分均≤2（0-10 分），且高倍镜视野下的嗜酸性粒细胞峰值计数＜5 个/高倍镜视野。在 6 周双盲阶段结束时未达到完全缓解的患者，可接受 6 周的 BOT 开放标签治疗（1 毫克，每日 2 次）。
在 6 周时，接受 BOT 治疗的患者中有 58%达到完全缓解，而接受安慰剂治疗的患者无一例达到完全缓解（P＜.0001）。接受 BOT 治疗的患者中有 93%达到组织学缓解，而接受安慰剂治疗的患者无一例达到组织学缓解（P＜.0001）。12 周后，85%的患者达到缓解。BOT 治疗 6 周和 12 周是安全且耐受良好的；接受 BOT 治疗的患者中有 5%出现症状性轻度念珠菌病，很容易用口服抗真菌药物治疗。
在一项针对活动期 EoE 成人患者的随机试验中，我们发现布地奈德口腔片剂在诱导临床和组织学缓解方面明显优于安慰剂。Eudra-CT 编号 2014-001485-99；ClinicalTrials.gov 注册号 NCT02434029。
