Albert J. Bredenoord’s research while affiliated with Amsterdam University Medical Center and other places

Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases (non-EoE EGIDs) are poorly understood. Evaluate clinical manifestations, diagnostics and treatment of non-EoE EGIDs at four hospitals in the Netherlands from 1991 to 2019. For this retrospective cohort study, centralized nationwide network and registry for cyto- and histopathology in the Netherlands (PALGA) was used. Seventy patients consented to participate. Median duration of follow up was 26 months, and median age was 36 years. About 44% had eosinophilic colitis (EoC) and 30% had > 1 GI location (multisite EGID). Most patients (91%) had mucosal type, 6% muscular and 3% serosal EGID. Three patients (4%) did not have follow up. Relapsing remitting in 21% (14/67) patients, with most being multisite (43%; 9/21). Single flares in 57% and chronically symptomatic in 22% of population. Concomitant atopy was seen in 29%. Normal endoscopy results in 61%; ileum was commonly identified normal area. Partial or complete symptom improvement to treatment seen in 71%. Results of the longitudinal retrospective Dutch study do not show progression from single site to multisite EGID or change in EGID type. We conclude that identifying patients requires further research as majority of patients had normal endoscopy and vague abdominal symptoms.

Background Eosinophilic esophagitis (EoE) is a chronic inflammatory and progressive fibrotic condition of the esophagus. There are limited treatment options for EoE and a substantial unmet need for effective and safe medical therapies. Drug development in EoE has been hampered by heterogeneous placebo response rates and uncertainty regarding appropriate endpoint configurations. Accurate characterization of placebo response in EoE randomized controlled trials (RCTs) will help inform more future efficient trial designs. Aims To conduct a systematic review and meta-analysis to characterize symptomatic, endoscopic, and histologic placebo response rates in placebo controlled EoE RCTs. Methods We updated a Cochrane systematic review and meta-analysis, searching MEDLINE, EMBASE, and CENTRAL to January 1, 2024, to identify placebo-controlled RCTs evaluating medical therapies for patients with EoE. Studies were screened independently by 2 reviewers, and full texts were then reviewed for eligibility; all data extracted in parallel. Primary outcome: pooled proportion of clinical, endoscopic, and histologic responders and remitters randomized to placebo, using an intention-to-treat approach and random-effects model. Potential sources of heterogeneity were explored using meta-regression. Results A total of 25 RCTs were included. The pooled proportion of clinical response was 40.9% [95% CI: 29.7%-52.8%] with substantial heterogeneity (I2=74.9%). On meta-regression, older age and a higher probability of being randomized to placebo reduced the likelihood of clinical response to placebo. The pooled proportion of histologic remission defined as a peak eosinophil count [PEC] ≤6 eosinophils per high power field [HPF] or ≤1 eos/HPF was 4.3% [95% CI: 2.6%-6.2%] (I2=23.6%) and 1.3% [95% CI: 0.5%-2.5%] (I2=0%), respectively. The mean difference in the EoE Endoscopic Reference score to placebo was -0.56 [95% CI: -0.91, -0.21]. Conclusions Over 1/3 of patients in EoE trials clinically respond to placebo and this is associated with trial design factors such as randomization ratio and trial population. Objective endoscopic and histologic measures are associated with lower placebo responses. These findings highlight the need to re-evaluate clinical trial endpoint configurations in EoE Table 1. Pooled proportion of placebo patients achieving response Abbreviations: CI confidence interval; eos eosinophils; hpf high power field Figure 3. Association between mean age of trial participants (A) and probability of receiving placebo (B) with proportion of clinical responders to placebo Funding Agencies None

Background: Standard treatments for eosinophilic esophagitis (EoE) may present adherence, tolerance, and efficacy challenges. Dupilumab 300 mg weekly is approved for the treatment of EoE in patients ≥ 1 year old, weighing ≥ 15 kg. This analysis aimed to evaluate dupilumab efficacy in patients from the LIBERTY EoE TREET trial (NCT03633617), with prior history of different EoE interventions. Research design and methods: This analysis included patients from Parts B/B - C of LIBERTY EoE TREET. Dupilumab efficacy was analyzed according to prior swallowed budesonide or fluticasone use and in those patients with previously trialed food elimination diet, esophageal dilation, or baseline proton pump inhibitor use, as stratified by prior swallowed topical corticosteroid (STC) use or STC inadequate response/intolerance/contraindication. Results: Dupilumab improved the proportion of patients achieving peak intraepithelial eosinophil count ≤ 6 eosinophils/high-power field, absolute change in Dysphagia Symptom Questionnaire score, and other histologic, symptomatic, and endoscopic endpoints vs. placebo at Week (W) 24, irrespective of prior swallowed budesonide/fluticasone use. Improvements were maintained at W52. Similar results were observed across the other subgroups. Conclusion: Dupilumab was efficacious in patients with EoE irrespective of prior treatments/interventions. Clinical trial registration: www.clinicaltrials.gov identifier is NCT03633617.