Effect of randomized treatment withdrawal of budesonide oral suspension on clinically relevant efficacy outcomes in patients with eosinophilic esophagitis: a post hoc analysis.

IF 3.9 3区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Therapeutic Advances in Gastroenterology Pub Date : 2024-12-23 eCollection Date: 2024-01-01 DOI:10.1177/17562848241307602

Evan S Dellon, Margaret H Collins, David A Katzka, Vincent A Mukkada, Gary W Falk, Wenwen Zhang, Bridgett Goodwin, Brian Terreri, Mena Boules, Nirav K Desai, Ikuo Hirano

{"title":"Effect of randomized treatment withdrawal of budesonide oral suspension on clinically relevant efficacy outcomes in patients with eosinophilic esophagitis: a post hoc analysis.","authors":"Evan S Dellon, Margaret H Collins, David A Katzka, Vincent A Mukkada, Gary W Falk, Wenwen Zhang, Bridgett Goodwin, Brian Terreri, Mena Boules, Nirav K Desai, Ikuo Hirano","doi":"10.1177/17562848241307602","DOIUrl":null,"url":null,"abstract":"Background: Relapse after corticosteroid withdrawal in eosinophilic esophagitis is not well understood.Objectives: Budesonide oral suspension (BOS) 2.0 mg twice daily (b.i.d.) was evaluated in two consecutive phase III studies (12 and 36 weeks, respectively). For clinicopathologic responders after 12 weeks of BOS treatment, we assessed randomized treatment withdrawal for up to 36 weeks of therapy.Design: Post hoc analysis of a phase III, double-blind, randomized withdrawal study.Methods: Clinicopathologic responders (⩽6 eosinophils per high-power field (eos/hpf) and ⩾30% reduction in Dysphagia Symptom Questionnaire (DSQ) score from baseline) after 12 weeks of BOS were randomized to continue BOS 2.0 mg b.i.d. (BOS-BOS) or withdraw to placebo (PBO; BOS-PBO) for up to 36 weeks. Relapsers (⩾15 eos/hpf (⩾2 esophageal regions) and ⩾4 days of dysphagia (DSQ)) could reinitiate BOS 2.0 mg b.i.d. This post hoc analysis assessed a more clinically relevant relapse definition (⩾15 eos/hpf (⩾1 esophageal region) and ⩾4 days of dysphagia (DSQ)) for BOS-BOS versus BOS-PBO patients over 36 weeks. To account for BOS-PBO patients who reinitiated BOS before week 36, patients' last observations before reinitiating BOS were carried forward (last observation carried forward (LOCF)) for histologic, symptom, and endoscopic efficacy endpoints (at weeks 12 and 36).Results: Of 48 patients included (BOS-BOS, n = 25; BOS-PBO, n = 23), significantly more BOS-PBO than BOS-BOS patients relapsed over 36 weeks using this post hoc relapse definition (60.9% vs 28.0%; p = 0.022). More BOS-BOS than BOS-PBO patients maintained histologic responses (all thresholds) and showed improvements in symptom and endoscopic efficacy endpoints.Conclusion: More BOS-PBO than BOS-BOS patients relapsed, determined by a more clinically relevant post hoc relapse definition. Using LOCF, more BOS-BOS than BOS-PBO patients also maintained or had improvements in efficacy endpoints.Trial registration: ClinicalTrials.gov identifiers (https://clinicaltrials.gov/): NCT02605837, NCT02736409.","PeriodicalId":48770,"journal":{"name":"Therapeutic Advances in Gastroenterology","volume":"17 ","pages":"17562848241307602"},"PeriodicalIF":3.9000,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11672502/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Therapeutic Advances in Gastroenterology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17562848241307602","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Relapse after corticosteroid withdrawal in eosinophilic esophagitis is not well understood.

Objectives: Budesonide oral suspension (BOS) 2.0 mg twice daily (b.i.d.) was evaluated in two consecutive phase III studies (12 and 36 weeks, respectively). For clinicopathologic responders after 12 weeks of BOS treatment, we assessed randomized treatment withdrawal for up to 36 weeks of therapy.

Design: Post hoc analysis of a phase III, double-blind, randomized withdrawal study.

Methods: Clinicopathologic responders (⩽6 eosinophils per high-power field (eos/hpf) and ⩾30% reduction in Dysphagia Symptom Questionnaire (DSQ) score from baseline) after 12 weeks of BOS were randomized to continue BOS 2.0 mg b.i.d. (BOS-BOS) or withdraw to placebo (PBO; BOS-PBO) for up to 36 weeks. Relapsers (⩾15 eos/hpf (⩾2 esophageal regions) and ⩾4 days of dysphagia (DSQ)) could reinitiate BOS 2.0 mg b.i.d. This post hoc analysis assessed a more clinically relevant relapse definition (⩾15 eos/hpf (⩾1 esophageal region) and ⩾4 days of dysphagia (DSQ)) for BOS-BOS versus BOS-PBO patients over 36 weeks. To account for BOS-PBO patients who reinitiated BOS before week 36, patients' last observations before reinitiating BOS were carried forward (last observation carried forward (LOCF)) for histologic, symptom, and endoscopic efficacy endpoints (at weeks 12 and 36).

Results: Of 48 patients included (BOS-BOS, n = 25; BOS-PBO, n = 23), significantly more BOS-PBO than BOS-BOS patients relapsed over 36 weeks using this post hoc relapse definition (60.9% vs 28.0%; p = 0.022). More BOS-BOS than BOS-PBO patients maintained histologic responses (all thresholds) and showed improvements in symptom and endoscopic efficacy endpoints.

Conclusion: More BOS-PBO than BOS-BOS patients relapsed, determined by a more clinically relevant post hoc relapse definition. Using LOCF, more BOS-BOS than BOS-PBO patients also maintained or had improvements in efficacy endpoints.

Trial registration: ClinicalTrials.gov identifiers (https://clinicaltrials.gov/): NCT02605837, NCT02736409.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

布地奈德口服混悬液随机停药对嗜酸性食管炎患者临床相关疗效结局的影响：事后分析

背景：嗜酸性食管炎患者停用糖皮质激素后是否复发尚不清楚。目的：布地奈德口服混悬液（BOS） 2.0 mg，每日两次（b.i.d）在两个连续的III期研究中进行评估（分别为12周和36周）。对于12周BOS治疗后的临床病理应答者，我们评估了长达36周的随机治疗停药。设计：一项III期、双盲、随机停药研究的事后分析。方法：在12周的BOS治疗后，临床病理应答者(每高倍视野（eos/hpf)≥6个嗜酸性粒细胞，并且吞咽困难症状问卷（DSQ）评分从基线减少了30%）被随机分配到继续每天2.0 mg BOS （BOS-BOS）或撤销安慰剂(PBO；BOS-PBO)治疗长达36周。复发者（大于或等于15 eos/hpf（大于或等于2个食管区域）和大于或等于4天的吞咽困难（DSQ））可以重新启动BOS 2.0 mg b.i.d。该事后分析评估了36周以上BOS-BOS与BOS- pbo患者的更临床相关的复发定义（大于或等于15 eos/hpf（大于或等于1个食管区域）和大于或等于4天的吞咽困难（DSQ））。为了解释在第36周之前重新启动BOS的BOS- pbo患者，将患者在重新启动BOS之前的最后一次观察（最后一次观察（LOCF））进行组织学，症状和内窥镜疗效终点（在第12周和第36周）。结果：纳入48例患者(BOS-BOS, n = 25；BOS-PBO, n = 23)，根据这一事后复发定义，BOS-PBO患者比BOS-BOS患者在36周内复发的人数显著增加(60.9% vs 28.0%；p = 0.022)。与BOS-PBO患者相比，更多的BOS-BOS患者维持了组织学反应（所有阈值），并在症状和内镜疗效终点上表现出改善。结论：BOS-PBO患者的复发率高于BOS-BOS患者，这是由更具有临床相关性的术后复发定义决定的。使用LOCF，更多的BOS-BOS患者比BOS-PBO患者也维持或改善了疗效终点。试验注册：ClinicalTrials.gov标识符（https://clinicaltrials.gov/）： NCT02605837, NCT02736409。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Therapeutic Advances in Gastroenterology GASTROENTEROLOGY & HEPATOLOGY-

CiteScore

6.70

自引率

2.40%

发文量

103

审稿时长

15 weeks

期刊介绍： Therapeutic Advances in Gastroenterology is an open access journal which delivers the highest quality peer-reviewed original research articles, reviews, and scholarly comment on pioneering efforts and innovative studies in the medical treatment of gastrointestinal and hepatic disorders. The journal has a strong clinical and pharmacological focus and is aimed at an international audience of clinicians and researchers in gastroenterology and related disciplines, providing an online forum for rapid dissemination of recent research and perspectives in this area. The editors welcome original research articles across all areas of gastroenterology and hepatology. The journal publishes original research articles and review articles primarily. Original research manuscripts may include laboratory, animal or human/clinical studies – all phases. Letters to the Editor and Case Reports will also be considered.