Active Eosinophilic Esophagitis Research Articles

The Minimally Invasive 1-Hr Esophageal String Test (EST) Monitors Therapeutic Changes in Mucosal Inflammation in Eosinophilic Esophagitis.

Endoscopy, standard-of-care for monitoring Eosinophilic Esophagitis (EoE), assesses mucosal inflammation. The Esophageal String Test (EST®), a minimally invasive swallowed capsule and immunoassays, quantifies EoE inflammation. We determined whether the EST/EoEScore can monitor disease in patients undergoing treatment. Thirty-three samples from 14 EoE patients (7 children, 7 adults) who underwent repeat endoscopies and ESTs were studied. Biopsies were analyzed for peak eosinophil counts; ESTs analyzed for EoEScores. Eosinophil counts and EoEScores significantly correlated during treatment, distinguishing patients with active EoE from treatment-associated remissions for 93.9% of ESTs performed. The EST can be used to longitudinally monitor responses to treatment in EoE.

Differing Epithelial and Immunologic Activation Patterns Following Food Reintroduction Reveal Different Transcriptional Profiles in Active Eosinophilic Esophagitis

Differing Epithelial and Immunologic Activation Patterns Following Food Reintroduction Reveal Different Transcriptional Profiles in Active Eosinophilic Esophagitis

S649 Design of the Phase 4 REMODEL Study Assessing the Effect of Dupilumab on Esophageal Function and Remodeling in Adult Patients With Active Eosinophilic Esophagitis

S649 Design of the Phase 4 REMODEL Study Assessing the Effect of Dupilumab on Esophageal Function and Remodeling in Adult Patients With Active Eosinophilic Esophagitis

Noninvasive Disease Assessment in Eosinophilic Esophagitis With Fractionated Exhaled Nitric Oxide, Blood, and Fecal Biomarkers.

Eosinophilic Esophagitis (EoE) is a chronic inflammatory condition of the esophagus triggered by food and aeroallergens. There is a need for noninvasive biomarkers that reliably detect EoE in patients with cardinal symptoms and predict treatment response to reduce endoscopic evaluations. Nonasthmatic patients 18 years or above with suspected or diagnosed EoE, gastroesophageal reflux disease (GERD), and control individuals with indication for endoscopy were enrolled prospectively between November 2020 and May 2022. Participants underwent body plethysmography with fractionated exhaled nitric oxide (FeNO) level measurement. Besides, serum and fecal biomarkers were measured by ELISA. A follow-up examination was scheduled after treatment initiation in patients with active EoE. The median FeNO level in active EoE (20 ppb) was higher compared with GERD (15 ppb, P=0.038) and control individuals (14 ppb, P=0.046). Median FeNO did not significantly differ in EoE patients who underwent follow-up assessment after treatment response (20 ppb vs. 18 ppb, P=0.771). Serum EDN, ECP, and the absolute eosinophil blood count (AEC) were elevated in active EoE compared with control individuals but not compared with GERD except for AEC. Serum EDN, ECP and AEC decreased in EoE in remission at follow-up assessment. None of the fecal biomarkers was elevated in active EoE or during treatment. Assessment of FeNO may have diagnostic value in differentiating patients with active EoE from non-EoE patients but is not a suitable marker for monitoring disease activity. Serum EDN, ECP, TARC, and AEC levels are emerging as potential candidates for monitoring disease activity in EoE.

Persistent Desmoglein-1 downregulation and Periostin accumulation in histologic remission of Eosinophilic Esophagitis

BackgroundPatients with Eosinophilic esophagitis (EoE) require long-lasting resolution of inflammation to prevent fibrostenosis and dysphagia. However, the dissociation between symptoms and histologic improvement suggests persistent molecular drivers despite histologic remission. ObjectiveTo characterize persisting molecular alterations in pediatric patients with EoE using tissue transcriptomics and proteomics. MethodsEsophageal biopsies (n=247) collected prospectively during 189 endoscopies from pediatric patients with EoE (N=36, up to 11 follow-up endoscopies) and pediatric controls (N=44, single endoscopies) were subjected to bulk transcriptomics (n=96) and proteomics (n=151). Intercellular junctions (Desmoglein-1/-3, Desmoplakin, E-cadherin) and epithelial-to-mesenchymal transition (EMT, Vimentin:E-cadherin ratio) were assessed by immunofluorescence staining. ResultsActive EoE (≥15 eosinophils/hpf), inactive EoE (<15 eosinophils/hpf) and deep remission EoE (0 eosinophils/hpf) were diagnosed in 107/185, 78/185 and 41/185 biopsies, respectively. Among the dysregulated genes (up-/downregulated 310/112) and proteins (up-/downregulated 68/16) between active EoE and controls, 17 genes and 6 proteins remained dysregulated in inactive EoE. Using persistently upregulated genes (n=9) and proteins (n=3) only, such as ALOX15, CXCL1, CXCL6, CTSG, CDH26, PRRX1, CLC, EPX, and POSTN was sufficient to separate inactive EoE, as well as deep remission biopsies from control tissue. While 32 differentially expressed genes persisted in deep remission of EoE compared to controls, the proteome normalized except for persistently upregulated Periostin (POSTN). Epithelial-mesenchymal transition normalized in inactive EoE, whereas desmosome recovery remained impaired due to Desmoglein-1 downregulation. ConclusionThe analysis of molecular changes shows persistent EoE-associated esophageal dysregulation despite histologic remission. These data expand our understanding of inflammatory processes and possible mechanisms that underlie tissue remodeling in EoE.

579. DUPILUMAB IMPROVES ENDOSCOPIC FEATURES OF EOSINOPHILIC OESOPHAGITIS IN CHILDREN WITH EOSINOPHILIC OESOPHAGITIS: 52-WEEK ANALYSIS OF THE EOE KIDS STUDY

Abstract Introduction Eosinophilic oesophagitis (EoE) is a chronic type 2 inflammatory disease. Dupilumab, a fully human monoclonal antibody that blocks drivers of type 2 inflammation, is approved in the USA for EoE patients aged ≥1 year, weighing ≥15 kg, and in the EU for adult and adolescent EoE patients aged ≥12 years, weighing ≥40 kg. The EoE-Endoscopic Reference Score (EREFS) is a validated tool for assessing oesophageal features of EoE, with subscores for inflammation and remodelling. This study assessed the impact of dupilumab on EREFS in children aged 1–&amp;lt;12 years with active EoE in the phase 3 EoE KIDS trial. Methods In Part A, 102 patients (mean [SD] age: 7.1 [3.05] years) were randomised 2:2:1:1 to receive weight-tiered dupilumab higher-exposure (HE) or lower-exposure, or placebo (two groups) for 16 weeks. In Part B, all patients received dupilumab at their preassigned dupilumab regimen for a further 36 weeks. This analysis focused on the dupilumab HE and placebo groups. EREFS were scored centrally by reviewers blinded to both treatment allocation and time point. Absolute change from baseline in EREFS total score (0−18), and EREFS inflammation (0−10) and remodelling (0−8) subscores were assessed at Weeks 16 and 52. Results A total of 37 and 34 patients received dupilumab HE and placebo, respectively; baseline mean EREFS scores were similar across treatment groups (6.8 vs 7.3) with EREFS inflammation subscores higher than remodelling subscores (6.0 vs 0.9 in the total population). EREFS total score was significantly reduced at Week 16 with dupilumab HE versus placebo (LS mean difference -3.8 [95% CI: -4.9, -2.6], P&amp;lt;0.0001), with improvement sustained through Week 52 in the dupilumab HE group (figure). Similar improvements were observed for EREFS inflammation subscore. Assessment of changes in remodelling was limited by low prevalence of fibrostenotic features in young children. Conclusion Dupilumab HE led to significant improvement in EREFS total score at Week 16 versus placebo, which was sustained through Week 52. Dupilumab HE also improved EREFS inflammation subscore.

One-food versus 4-food elimination diet for pediatric eosinophilic esophagitis: A multisite randomized trial

BackgroundA 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively impact quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy. ObjectiveWe performed a multi-site, randomized comparative efficacy trial of a 1-food (milk) elimination diet (1FED) versus 4-food (milk, egg, wheat, soy) elimination diet (4FED) in pediatric EoE. MethodsPatients aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to 1FED or 4FED for 12 weeks. Primary endpoint was symptom improvement by Pediatric EoE Symptom Score (PEESSv2.0). Secondary endpoints were proportion achieving histologic remission (<15 eosinophils/high-power field [eos/hpf]); change in histologic features (histology scoring system [HSS]), endoscopic severity (endoscopic reference score [EREFS]), transcriptome (EoE diagnostic panel [EDP]), and QoL scores; and predictors of remission. Results63 patients were randomly assigned to 1FED (n=38) and 4FED (n=25). In 4FED versus 1FED, mean PEESSv2.0 improved -25.0 versus -14.5 (p=0.04) but remission rates (41% versus 44%; p=1.00), HSS (-0.25 versus -0.29; p=0.77), EREFS (-1.10 versus -0.58; p=0.47) and QoL scores were similar between groups. The EoE transcriptome normalized in histologic responders to both diets. Baseline peak eosinophil count predicted remission (OR 0.975, 95% CI 0.953–0.999, p=0.04; cut-off ≤42 eos/hpf). The 4FED withdrawal rate (32%) exceeded 1FED (11%) (p=0.0496). ConclusionsAlthough 4FED moderately improved symptoms compared to 1FED, the histologic, endoscopic, QoL, and transcriptomic outcomes were similar in both groups. 1FED is a reasonable first choice therapy for pediatric EoE given its effects, tolerability, and relative simplicity.

Utilization and impact of esophageal string testing in children with eosinophilic esophagitis: A 1 year experience.

The 1-h esophageal string test (EST) is a minimally invasive test that can be used to monitor eosinophilic esophagitis (EoE) disease activity and guide treatment without endoscopy. We aimed to describe the real-world utilization and impact of EST on the care of children with EoE over the first year this was used at our center. Between 12/1/2022 and 11/30/2023, 39 ESTs were successful in 45 attempts (87% completion rate) in 31 patients. Five patients underwent multiple ESTs. Adverse events during the EST included vomiting. Reasons for failure to complete the EST (13%, n = 6) were patients could not swallow the capsule (n = 5) and vomiting (n = 1). EST was used to assess EoE without the need for endoscopy in 95% (n = 37) of cases. Treatment approach varied based on whether the EST indicated active (38.5%) or inactive (61.5%) EoE. The EST is a well-tolerated minimally invasive disease monitoring tool for patients with EoE.

Dupilumab for Eosinophilic Esophagitis in Patients 1 to 11 Years of Age

BackgroundDupilumab is a human monoclonal antibody that blocks interleukin-4 and interleukin-13 pathways and has shown efficacy in five different atopic diseases marked by type 2 inflammation, including eosinophilic esophagitis in adults and adolescents.MethodsIn this phase 3 trial, we randomly assigned, in a 2:2:1:1 ratio, patients 1 to 11 years of age with active eosinophilic esophagitis who had had no response to proton-pump inhibitors to 16 weeks of a higher-exposure or lower-exposure subcutaneous dupilumab regimen or to placebo (two groups) (Part A). At the end of Part A, eligible patients in each dupilumab group continued the same regimen and those in the placebo groups were assigned to higher-exposure or lower-exposure dupilumab for 36 weeks (Part B). At each level of exposure, dupilumab was administered in one of four doses tiered according to baseline body weight. The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16. Key secondary end points were tested hierarchically.ResultsIn Part A, histologic remission occurred in 25 of the 37 patients (68%) in the higher-exposure group, in 18 of the 31 patients (58%) in the lower-exposure group, and in 1 of the 34 patients (3%) in the placebo group (difference between the higher-exposure regimen and placebo, 65 percentage points [95% confidence interval {CI}, 48 to 81; P<0.001]; difference between the lower-exposure regimen and placebo, 55 percentage points [95% CI, 37 to 73; P<0.001]). The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic, and transcriptomic measures as compared with placebo. The improvements in histologic, endoscopic, and transcriptomic measures between baseline and week 52 in all the patients were generally similar to the improvements between baseline and week 16 in the patients who received dupilumab in Part A. In Part A, the incidence of coronavirus disease 2019, nausea, injection-site pain, and headache was at least 10 percentage points higher among the patients who received dupilumab (at either dose) than among those who received placebo. Serious adverse events were reported in 3 patients who received dupilumab during Part A and in 6 patients overall during Part B.ConclusionsDupilumab resulted in histologic remission in a significantly higher percentage of children with eosinophilic esophagitis than placebo. The higher-exposure dupilumab regimen also led to improvements in measures of key secondary end points as compared with placebo. (Funded by Sanofi and Regeneron Pharmaceuticals; EoE KIDS ClinicalTrials.gov number, NCT04394351.)

Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis

BackgroundBenralizumab is an eosinophil-depleting anti–interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear.MethodsIn a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24.ResultsA total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, –1.4 to 7.4; P=0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events.ConclusionsIn this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.)

Differential Contributions of Fibroblast Subpopulations to Intercellular Communication in Eosinophilic Esophagitis.

Fibroblast heterogeneity remains undefined in eosinophilic esophagitis (EoE), an allergic inflammatory disorder complicated by fibrosis. We utilized publicly available single-cell RNA sequencing data (GSE201153) of EoE esophageal biopsies to identify fibroblast sub-populations, related transcriptomes, disease status-specific pathways and cell-cell interactions. IL13-treated fibroblast cultures were used to model active disease. At least 2 fibroblast populations were identified, F_A and F_B. Several genes including ACTA2 were more enriched in F_A. F_B percentage was greater than F_A and epithelial-mesenchymal transition upregulated in F_B vs. F_A in active and remission EoE. Epithelial-mesenchymal transition was also upregulated in F_B in active vs. remission EoE and TNF-α signaling via NFKB was downregulated in F_A. IL-13 treatment upregulated ECM-related genes more profoundly in ACTA2- fibroblasts than ACTA2+ myofibroblasts. After proliferating epithelial cells, F_B and F_A contributed most to cell-cell communication networks. ECM-Receptor interaction strength was stronger than secreted or cell-cell contact signaling in active vs. remission EoE and significant ligand-receptor pairs were driven mostly by F_B. This unbiased analysis identifies at least 2 fibroblast sub-populations in EoE in vivo, distinguished in part by ACTA2. Fibroblasts play a critical role in cell-cell interactions in EoE, most profoundly via ECM-receptor signaling via the F_B sub-group.

Manometric findings in children with eosinophilic esophagitis and persistent post-remission dysphagia.

Dysphagia is a frequent symptom of active eosinophilic esophagitis (EoE), but at times it persists despite attaining histologic healing and lack of fibro-stenotic changes. We aimed to describe the manometric findings in this subset of patients. A retrospective review of charts between 2013 and 2023 at a tertiary pediatric gastroenterology center, treating roughly 1500 EoE patients per year. We included children with EoE referred to high-resolution impedance manometry (HRIM) for persistent dysphagia despite histologic healing (i.e., <15 eosinophils/high-power field [Eos/hpf]). Data including initial EoE diagnosis, endoscopy reports, esophageal biopsies, treatment regimens, and HRIM were retrospectively collected. The estimated prevalence of post-remission dysphagia in our cohort was exceedingly rare (<0.05%). Four patients met the eligibility criteria of histologic remission and absence of fibro-stenotic features on endoscopic evaluation and thus, were included in this case series. Patients achieved remission with steroids, proton-pump inhibitor, or both within a median time of 5 months from diagnosis. Peak Eosinophil count at remission was ≤5 Eos/hpf in three patients and ≤10 Eos/hpf in one. On HRIM, all four patients had a hypomotile esophagus and abnormal bolus clearance. Lower esophageal sphincter integrated relaxation pressure values were normal in three patients and elevated in one. Two patients were diagnosed with ineffective esophageal motility, one with aperistalsis and one with achalasia type 1. Post-remission dysphagia is rare in EoE. Esophageal dysmotility with a hypomotile pattern may contribute to the persistent dysphagia in children with EoE. HRIM should be considered in patients with EoE in whom symptoms persist despite histologic remission.

Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis

BackgroundThe mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. ObjectiveWe examined the correlation of a validated, patient-reported outcome (PRO) metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. MethodsData were extracted from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Patients were subgrouped by esophageal dilation history. We compared a validated PRO metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We utilized single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. ResultsThe EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31, P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3, P < .05). Of these, 11 were expressed in non-epithelial cells and 3 in epithelial cells; during histologic remission, only 4/11 (36%) non-epithelial versus 3/3 (100%) epithelial genes had decreased expression to <50% of that in active EoE. Fibroblasts expressed 5/11 (45%) non-epithelial EEsAI-associated EDP genes. A subset of non-epithelial (8/11, 73%), but not EoE-representative (0/4, 0%; CCL26, CAPN14, DSG1, SPINK7), genes was upregulated in patients with EoE with the highest versus lowest symptom burden. ConclusionThe correlation of symptoms and non-epithelial esophageal gene expression substantiates that non-epithelial cells (e.g., fibroblasts) likely contribute to symptom severity.

An esophagus cell atlas reveals dynamic rewiring during active eosinophilic esophagitis and remission.

Coordinated cell interactions within the esophagus maintain homeostasis, and disruption can lead to eosinophilic esophagitis (EoE), a chronic inflammatory disease with poorly understood pathogenesis. We profile 421,312 individual cells from the esophageal mucosa of 7 healthy and 15 EoE participants, revealing 60 cell subsets and functional alterations in cell states, compositions, and interactions that highlight previously unclear features of EoE. Active disease displays enrichment of ALOX15+ macrophages, PRDM16+ dendritic cells expressing the EoE risk gene ATP10A, and cycling mast cells, with concomitant reduction of TH17 cells. Ligand-receptor expression uncovers eosinophil recruitment programs, increased fibroblast interactions in disease, and IL-9+IL-4+IL-13+ TH2 and endothelial cells as potential mast cell interactors. Resolution of inflammation-associated signatures includes mast and CD4+ TRM cell contraction and cell type-specific downregulation of eosinophil chemoattractant, growth, and survival factors. These cellular alterations in EoE and remission advance our understanding of eosinophilic inflammation and opportunities for therapeutic intervention.

Characterization of lamina propria remodeling in pediatric eosinophilic esophagitis using second harmonic generation microscopy

Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by an intense infiltration of eosinophils into the esophageal epithelium. When not adequately controlled, eosinophilic inflammation can lead to changes in components of the extracellular matrix (ECM) of the lamina propria. Particularly, alterations to the collagen fiber matrix can lead to lamina propria fibrosis (LPF), which plays an important role in the fibrostenotic complications of EoE. Current approaches to assess LPF in EoE are prone to inter-observer inconsistencies and provide limited insight into the structural remodeling of the ECM. An objective approach to quantify LPF can eliminate inter-observer inconsistencies and provide novel insights into the fibrotic transformation of the lamina propria in EoE. Second harmonic generation (SHG) microscopy is a powerful modality for objectively quantifying disease associated alterations in ECM collagen structure that is finding increasing use for clinical research. We used SHG with morphometric analysis (SHG-MA) to characterize lamina propria collagen fibers and ECM porosity in esophageal biopsies collected from children with active EoE (n = 11), inactive EoE (n = 11), and non-EoE (n = 11). The collagen fiber width quantified by SHG-MA correlated positively with peak eosinophil count (r = 0.65, p < 0.005) and histopathologist scoring of LPF (r = 0.52, p < 0.005) in the esophageal biopsies. Patients with active EoE had a significant enlargement of ECM pores compared to inactive EoE and non-EoE (p < 0.005), with the mean pore area correlating positively with EoE activity (r = 0.76, p < 0.005) and LPF severity (r = 0.65, p < 0.005). These results indicate that SHG-MA can be utilized to objectively characterize and provide novel insights into lamina propria ECM structural remodeling in children with EoE, which could aid in monitoring disease progression.

Outcomes of Serum Food-Specific Immunoglobulin G 4 to Guide Elimination Diet in Patients With Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.

Pharmacologic Treatment of Eosinophilic Esophagitis: Efficacious, Likely Efficacious, and Failed Drugs.

Eosinophilic esophagitis (EoE) is a chronic, food allergen-mediated, esophageal disease that will lead, if left untreated, to esophageal remodeling. As such, the vast majority of EoE patients need treatment. Treatment strategies include drugs, food elimination diets, and esophageal dilation. This review focuses on pharmacologic options for treatment of EoE. Orodispersible budesonide tablets (Jorveza®) have been approved by regulatory authorities for EoE treatment of adults in Europe, Canada, and Australia, but not in the USA. Jorveza®, as compared to placebo, is effective in inducing and maintaining histologic and clinical remission over time. An orodispersible budesonide suspension (BOS, Eohilia®) was recently approved in the USA as induction treatment (12 weeks) in adolescents of at least 11 years and adults with active EoE. Before the approval of Jorveza® and Eohilia®, several investigator-initiated randomized controlled clinical studies evaluated esophagus-targeted formulations of either budesonide or fluticasone to treat pediatric and adult EoE patients. These drugs were generally efficacious in inducing and maintaining histological and clinical remission. Proton-pump inhibitors (PPIs) are used off-label for EoE treatment of pediatric and adult EoE patients given that they are able to induce histologic and clinical remission. However, when compared to the moderate certainty of evidence with regard to the failure to achieve histologic remission with swallowed topical corticosteroids, the certainty of evidence for PPIs is very low with very inconsistent results in absolute terms. Dupilumab (Dupixent®), a monoclonal antibody targeted against IL-4 and IL-13, was approved by regulatory authorities in the USA, Europe, Canada, but not yet Australia. In Europe, including Switzerland, Dupixent® is approved to treat EoE patients of at least 12 years of age with at least 40 kg body weight if they are either unresponsive or intolerant to or not candidates for conventional EoE therapies. Due to lack of efficacy or unfavorable safety profile, the following drugs are not recommended for EoE treatment: systemic steroids, sodium cromoglycate, montelukast, azathioprine, TNF-antagonists (e.g., infliximab), vedolizumab (mAb against α4β7), benralizumab (mAb against IL-5 receptor), mepolizumab (mAb against IL-5), reslizumab (mAb against IL-5), omalizumab (mAb against IgE), and lirentelimab (mAb against Siglec-8). Long-term effectiveness and safety data on different drugs are currently sparse. Concerted efforts of different stakeholders will be necessary to continue the endeavor of providing our patients with much-needed therapies.

Monitoring pediatric eosinophilic esophagitis disease activity using an unsedated blind esophageal brushing model: A pilot study.

Recurrent upper endoscopies are essential for monitoring therapy response and disease activity in patients with eosinophilic esophagitis (EoE), leading to increased costs, procedural complications, and anesthesia exposure. The aim of this study was to examine an office-based model using serial sedation-free blind esophageal epithelial brushing (BEEB) to monitor therapy response through eosinophil-derived neurotoxin (EDN) levels and guide therapy plans in pediatric EoE patients. EoE patients (≤21 years of age) were enrolled in this prospective study. Subjects were placed on dietary, pharmacologic, or combination therapy with the goal of inducing or maintaining remission. To assess response to sequential interventions, subjects underwent sequential sedation-free BEEBs through nasogastric tubesto measure EDN levels. Based on serial brushings, an individual plan of diet, medications, or a combination of both was created for each subject, and a final endoscopy was then performed to validate the accuracy of the individual plans. Twenty-four subjects completed the study. The average peak eosinophil countin patients with active EoE was 58.1 ± 30.8 eosinophils per high-power field and mean EDN level was 165.2 ± 191.3 μg/mL. A total of 42 BEEBs were completed. Individual therapy plans based on sequential BEEB were accurate in 19 out of the 24 patients (79%) and specifically nine out of 10 patients (90%) treated with elimination diets. This study suggests that office-based sedation-free BEEBs can be used to monitor therapy response and disease activity in pediatric EoE patients.

Esophageal Remodeling Correlates With Eating Behaviors in Pediatric Eosinophilic Esophagitis.

There are limited data characterizing eating habits among pediatric patients with eosinophilic esophagitis (EoE). We compared eating behaviors in pediatric patients with EoE with healthy controls and assessed the degree of correlation with symptomatology, endoscopic and histologic findings, and esophageal distensibility. We conducted a prospective, observational study where subjects consumed 4 food textures (puree, soft solid, chewable, and hard solid) and were scored for eating behaviors including number of chews per bite, sips of fluid per food, and consumption time. Symptomatic, endoscopic, histologic, and esophageal distensibility data were collected for case subjects. Twenty-seven case subjects and 25 healthy controls were enrolled in our study (mean age 11.0 years, 63.5% male). Compared with healthy controls, pediatric patients with EoE demonstrated more chews per bite with soft solid (13.6 vs 9.1, P = 0.031), chewable (14.7 vs 10.7, P = 0.047), and hard solid foods (19.0 vs 12.8, P = 0.037). Patients with EoE also demonstrated increased consumption time with soft solid (94.7 vs 58.3 seconds, P = 0.002), chewable (90.0 vs 65.1 seconds, P = 0.005), and hard solid foods (114.1 vs 76.4 seconds, P = 0.034) when compared with healthy controls. Subgroup analysis based on disease status showed no statistically significant differences in eating behaviors between active and inactive EoE. Total endoscopic reference score positively correlated with consumption time ( r = 0.53, P = 0.008) and number of chews ( r = 0.45, P = 0.027) for chewable foods and with number of chews ( r = 0.44, P = 0.043) for hard solid foods. Increased consumption time correlated with increased eosinophil count ( r = 0.42, P = 0.050) and decreased esophageal distensibility ( r = -0.82, P < 0.0001). Altered eating behaviors including increased chewing and increased consumption time can be seen in pediatric patients with EoE, can persist despite histologic remission, and may be driven by changes in esophageal distensibility.

In Vivo Raman Spectroscopy Reveals Biochemical Composition of the Esophageal Tissue in Pediatric Eosinophilic Esophagitis.

Biochemical alterations in the esophagus of patients with eosinophilic esophagitis (EoE) are poorly understood. We used Raman spectroscopy through a pediatric endoscope to identify key Raman features reflective of the esophageal biochemical composition to differentiate between children with EoE from non-EoE controls and between children with active (aEoE) and inactive EoE (iEoE). Spectral measurements were obtained using a customized pediatric endoscope-compatible fiber-optic Raman probe in real time during an esophagogastroduodenoscopy. Chemometric analysis was performed to identify key Raman features associated with EoE. Pearson correlation analysis was used to assess relationship between the key Raman features and EoE activity indices. Their diagnostic utility was ascertained using the receiver operator characteristic curve analysis. Forty-three children were included in the study (EoE = 32 [74%] and non-EoE control = 11 [26%]; aEoE = 20 [63%] and iEoE = 12 [37%]). Raman intensities assigned to lipids, proteins, and glycogen:protein ratio accurately distinguished children with EoE from those without EoE and aEoE from iEoE. They significantly correlated with EoE activity indices. The Raman peak ratio for lipids had 90.6% sensitivity, 100% specificity, and an area under the curve of 0.95 to differentiate children with EoE from non-EoE controls. The glycogen:protein ratio had 70% sensitivity, 91.7% specificity, and an area under the curve of 0.75 to distinguish children with aEoE from iEoE. Real-time intraendoscopy Raman spectroscopy is an effective method for identifying spectral markers reflective of the esophageal biochemical composition in children with EoE. This technique may aid in the diagnosis and monitoring of EoE and help to elucidate EoE pathogenesis.