Real-World Infectious Outcomes with Dupilumab Compared with Proton Pump Inhibitors and Topical Steroids in Eosinophilic Esophagitis: A Multi-cohort Propensity Matched Analysis.

Efficacy of Therapy for Eosinophilic Esophagitis in Real-World Practice

Background Eosinophilic esophagitis (EoE) is characterized by eosinophilic infiltration in the esophageal epithelium that causes esophageal dysfunction-related symptoms. The treatment for EoE includes acid suppressants (proton pump inhibitors (PPIs) or potassium competitive acid blocker (P-CAB)), topical corticosteroid (TCS), and diet therapy. In addition, biologics (i.e. dupilumab) have been recently approved for EoE in the US. However, the appropriate initial and maintenance therapy for EoE have not been established yet. Therefore, the aim of the study was to investigate the treatment pattern of EoE and its association with fibrostenosis in Japan. Methods We investigated prescription pattern for EoE analyzing an employer-based health insurance claim database from 2005 to 2022. EoE cases were identified based on the International Classification of Diseases-tenth Revision code, K20.0. The initial treatment of interest for EoE included PPIs, P-CAB, and TCS (swallowed inhaled CS). The initial treatment for EoE was defined as these drugs prescribed within two months from the index date of EoE diagnosis. The discontinuation rates of initial PPIs or P-CAB were analyzed using Kaplan-Meier method. The discontinuation of treatment was defined as no treatment following within 90 days from the prescription of the previous treatment. Results Overall, 984 EoE patients (45 years old [38-52], male 747 [75.9%]) were ultimately analyzed. Most of the initial treatment for EoE was acid suppressants (PPIs [323 54.9%], P-CAB [241, 41%]), followed by TCS (13, 2.2%) and combination therapy of PPIs or P-CAB and TCS (11, 1.9%). PPIs or P-CAB discontinued in approximately 50% and 70% of the cases at approximately 150 days and 720 days respectively from the start of the initial therapy. The switching to the second-line therapy from the initial PPIs or P-CAB rarely happened. During the observation period, no EoE patients developed esophageal stenosis. Conclusion PPIs or P-CAB were most prescribed as the initial treatment for EoE in Japan. In addition, more than half of EoE patients discontinued such initial therapy within 2 years without fibrostenotic complication. These findings indicate that EoE that can respond to initial acid suppressants therapy does not necessarily require the maintenance therapy to prevent esophageal fibrostenosis.

Background: Eosinophilic esophagitis (EoE) is a disorder of the esophagus that has become increasingly recognized in children. Because these children undergo multiple endoscopies, discovering a non-invasive biomarker of disease activity is highly desirable. The aim of this study was to use targeted plasma metabolomics to identify potential biomarker candidates for EoE in a discovery phase.Methods: A prospective, single-center clinical trial was performed on 24 children ages 2–18 years with and without EoE undergoing upper endoscopy for any indication. Blood samples were collected for metabolomics profiling using the subclasses: amino acids, tricarboxylic acid cycle, acetylation, and methylation. Using mass spectrometry and systematic bioinformatics analysis, 48 metabolites were measured and compared between children with active EoE (+EoE) and controls (–EoE). To investigate the effect of proton pump inhibitor (PPI) use on metabolites, patients were also stratified based on PPI use (+PPI, –PPI).Results: Seven children had active EoE at the time of endoscopy. Eleven children were on PPI (4 with EoE). Of the 48 metabolites measured, 8 plasma metabolites showed statistically significant differences (p < 0.05) comparing +EoE –PPI to –EoE –PPI, a few of which were upregulated metabolites involved in the urea cycle. There were 14 significant differences comparing +EoE +PPI to +EoE –PPI. This demonstrated that in EoE patients, PPI use upregulated metabolites involved in the urea cycle, while it downregulated metabolites involved in methylation. Comparison among all four groups, +EoE +PPI, +EoE –PPI, –EoE +PPI, and –EoE –PPI, revealed 27 significantly different metabolites. +EoE +PPI had downregulated methionine and N-acetyl methionine, while both +EoE groups and –EoE +PPI had upregulated homocysteine, N-acetylputrescine, N-acetylornithine, arginine, and ornithine.Conclusion: The present study revealed key plasma metabolite differences in children with EoE compared to unaffected controls. Notable candidate biomarkers include dimethylarginine, putrescine, and N-acetylputrescine. PPI use was shown to influence these urea cycle metabolites, regardless of EoE presence. Therefore, future studies should distinguish patients based on PPI use or determine metabolites while not on treatment. These findings will be confirmed in a larger validation phase, as this may represent a significant discovery in the search for a non-invasive biomarker for EoE.Clinical Trial Registration: This clinical trial was registered with ClinicalTrials.gov, identifier: NCT 03107819.

E osinophilic esophagitis (EoE) is an immune-mediated disorder trig- gered by food or other environmental antigens. EoE presents with food impaction and dysphagia in adults. In children, the symptoms may be more diverse including failure to thrive, vomiting, gagging and gastroesophageal reflux-like symptoms. Overall, the prevalence of EoE in the general population is approximately 50 per 100,000. EoE is mediated by T helper cell 2 cytokines such as interleukin (IL)-4, IL-5 and IL-13, which promote eosinophil recruitment via eotaxin-3 (1).

Index of Suspicion

IntroductionThe prevalence of Eosinophilic Oesophagitis (EoE) is rising. Pharmacological options were limited and practitioners have relied on proton pump inhibitors (PPI) and swallowed ‘topical’ steroids (TS) with limited data on...

Eosinophilic esophagitis is characterized by eosinophil inflammation restricted to the esophagus and the resulting symptoms of esophageal dysfunction. Critical to the diagnosis of eosinophilic esophagitis is a trial of proton pump inhibitor therapy to exclude alternative causes of esophageal eosinophilia such as proton pump inhibitor-responsive esophageal eosinophilia. While consensus guidelines recommend a proton pump inhibitor trial prior to diagnosis, little is known about its implementation in clinical practice. The primary aim of this study is to assess the frequency of proton pump inhibitor trial prior to the diagnosis of eosinophilic esophagitis in community practice. The secondary aim is to assess the frequency of other treatments for eosinophilic esophagitis, including topical steroids and/or dietary therapy, in patients who did not undergo a proton pump inhibitor trial prior to diagnosis or who had an alternative diagnosis to eosinophilic esophagitis upon completed workup. We conducted a single-center, case series of patients referred to the Hospital of the University of Pennsylvania for eosinophilic esophagitis management between 2010 and 2015. This case series consisted of 125 patients who were referred from community practitioners with a presumptive diagnosis of eosinophilic esophagitis. Upon review, 90 out of 125 (72%) patients had not had a proton pump inhibitor trial or esophageal pH testing prior to the diagnosis of eosinophilic esophagitis being made. Of these patients, 77.8% (70/90) had already received either topical steroid or dietary therapy for presumed eosinophilic esophagitis. Of the 125 patients initially diagnosed with eosinophilic esophagitis, 32 (25.6%) were found to have an alternative diagnosis, and 79.2% of this subset of patients (25/32) had previously received topical steroid or dietary therapy. This study demonstrates that a substantial number of patients with presumed eosinophilic esophagitis have not had a proton pump inhibitor trial prior to diagnosis in community practice. This led to the misclassification of patients and potentially to the use of less optimal medical therapies in a substantial number of these patients.

Introduction Since recently, after detection of eosinophilic predominant inflammation of esophagus a trial with proton-pump inhibitors (PPIs) was needed to individuate children with PPI-responsive esophageal eosinophilia (PPI-REE), only those non-responders received eosinophilic esophagitis (EoE) diagnosis. In 2018 updated international consensus suggested removing the PPI trial as a diagnostic criterion and consider PPIs as a treatment together with diets and topical steroids. The role of PPIs is evaluated in children with esophageal atresia (EA) and EoE versus EoE from general population. Method A retrospective chart review of both children with EA and EoE followed-up from at January 2005 has been performed. According to ESPGHAN guidelines published in 2014 patients showing eosinophilic inflammation received high-dose PPI trial to identified PPI-REE. Those non-responders were labeled as EoE and underwent to dietary and/or topical steroid treatment. Demographics and disease characteristics of EA patients with EoE were analyzed and compared with those with EoE from general population. Results Overall, 370 EA and 118 EoE patients were analyzed. Of them 15 EA-EoE patients were detected. Consequently, in our cohorts, 4.0% of EA patients developed EoE. Male-to-female prevalence ratio was of 2.55 with no difference in gender prevalence between groups. At diagnosis EoE-EA children were significantly younger compared to EoE group (mean: 5.1 vs 10.8 years; P &lt; 0.0001). Peak EOS/HPF at diagnosis did not differ between groups (50.1 ± 26 vs 59.8 ± 29 EOS/HPF). No difference was observed in allergy prevalence between groups (53.8 vs 68.0%). PPI-REE was significantly more prevalent in EA-EoE group that in EoE group (66.6% vs 19.4%; P = 0.0004). Conclusion Similar gender distribution and high prevalence of allergy suggest that common genetic susceptibility factors for EoE exist. However, high prevalence of PPI-REE coupled early EoE onset might also suggest that other factors (e.g. esophageal motility disorders) might play a physiopathological role in EoE development in EA children. Our study suggests that a stepwise approach with PPIs as a first-line treatment for EoE management in EA children should still be considered.

Anti–TNF-α (infliximab) therapy for severe adult eosinophilic esophagitis

Purpose: Proton pump inhibitors (PPI) are used in patients with Eosinophilic Esophagitis (EoE) to fulfill diagnostic criteria, as well as for treatment. PPI’s therapeutic effect appears to involve anti-inflammatory mechanisms, specifically its ability to downregulate the expression of the chemoattractant eotaxin-3 through an acid-independent pathway. A recent in-vitro study showed greater suppression of eotaxin-3 in esophageal cells derived from EoE patients when they were treated with both fluticasone and omeprazole together, than when treated with either drug alone. Our aim was to compare the histologic outcomes of EoE patients between those …

Onset of eosinophilic esophagitis during a clinical trial program of oral immunotherapy for peanut allergy

Effect of Six-Food Elimination Diet on Clinical and Histologic Outcomes in Eosinophilic Esophagitis

Eosinophilic esophagitis (EoE) is an antigen-mediated inflammatory esophageal disease that is commonly treated with high-dose proton-pump inhibitors (PPIs), topical corticosteroids, or food elimination diet (FED) monotherapy. Combination treatment has not been well studied in the management of EoE. We aimed to determine if PPI and FED combination therapy was able to induce histologic remission in patients with EoE refractory to monotherapy. We conducted a retrospective cohort study identifying patients with EoE that was refractory to PPI monotherapy and FED monotherapy but histologically responsive to PPI and FED combination therapy. We also identified symptom changes through chart review. Out of 405 EoE patients, 12 patients were identified with EoE that was refractory to PPI monotherapy and FED monotherapy but histologically responsive to PPI and FED combination therapy. Out of 12 patients, 11 (91.67%) noted resolution of symptoms while on combination therapy. Comparative analysis of peak eosinophil counts showed that patients achieved a median of 4.5 eos/hpf (interquartile range [IQR], 2-6.5), which was significantly decreased compared to baseline (median, 45; IQR, 35.5-50; Wilcoxon signed-rank test, P < .001), PPI monotherapy (median, 41; IQR, 26-50; Wilcoxon signed-rank test, P < .001), and FED monotherapy (median, 45; IQR, 17-67.5; Wilcoxon signed-rank test, P < .001). Our work shows that patients with EoE refractory to PPI monotherapy and FED monotherapy can successfully achieve histologic remission and symptom benefit with PPI and FED combination therapy. Therefore, combination therapy should be considered a viable option for patients with EoE who fail treatment with first-line monotherapies.

Background Eosinophilic oesophagitis (EO) is a recently described allergic condition characterised by oesophageal dysmotility with progression to stricture formation in severe cases. Diagnosis is histological, based on >15 per high-powered field in oesophageal biopsies. Treatment options remain limited to dietary modification (including elemental feeds), proton pump inhibitors (PPI) and topical/systemic steroids. There is sparse population data on the condition. To report demographic data on children with EO, establish the current burden of disease and review effectiveness of treatments with clinical and histopathological outcomes. Methods All patients diagnosed with EO between 2008–2013 in RHSC Glasgow were retrospectively identified by joint review of all oesophageal histopathology reports (n = 1060) with a Consultant Paediatric Pathologist (DP) and findings correlated with clinical symptoms, treatment and outcomes. Data was analysed using Microsoft Excel 2007 and SPSS version 22.0. Results Within the West of Scotland 30 children (mean age 9.1, range 0.7–15.2) were diagnosed with EO between January 2008 and May 2013 with no obvious increase in annual incidence. 22 (73%) were male. The most common presenting symptoms were abdominal pain (43%), vomiting (37%) and dysphagia (33%), with food bolus obstruction in 27%. Most (77%) had concurrent atopic disease. At diagnosis the mean number of oesophageal eosinophils per high-powered field was 61, ascertained with a mean of 5 biopsies from 3 different oesophageal regions. The mean peripheral eosinophil count at diagnosis was 1.8 (range 0.0–27.0). PPIs were clinically effective in 19/21 (70%) patients and 14/16 showed histological improvement. All 17 patients receiving dietary therapy demonstrated clinical improvement and 14/15 showed histological improvement; 11 (40%) had topical steroids, clinically effective in 10/11 patients with 7/9 showing histological improvement. However, 4 (13%) progressed to oral steroids. There was considerable overlap between treatments. At one year follow-up 93% were clinically improved and 86% showed endoscopic improvement. Conclusions The total numbers of patients diagnosed was surprisingly small. Whilst treatment with PPI is effective, most patients also required dietary or steroid therapy. A significant number required oral steroids. A departmental guideline is being developed on the basis of these results and further work is required to establish frequency of repeat endoscopy.

Consensus diagnostic recommendations to distinguish GORD from eosinophilic oesophagitis (EoE) by response to a trial of proton pump inhibitors (PPIs) unexpectedly uncovered an entity called ‘PPI-responsive oesophageal eosinophilia’ (PPI-REE). PPI-REE...