Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis.

BACKGROUND: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear. METHODS: In 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. RESULTS: A 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. CONCLUSIONS: In 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.).

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

BACKGROUND: Dupilumab 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. METHODS: In 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. RESULTS: In 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. CONCLUSIONS: Dupilumab 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.).

Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis.

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis. METHODS: We conducted a three-part, phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (Part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo (Part B) up to week 24. Eligible patients who completed Part A or Part B continued the trial in Part C, in which those who completed Part A received dupilumab at a weekly dose of 300 mg up to week 52 (the Part A-C group); Part C that included the eligible patients from Part B is ongoing. The two primary end points at week 24 were histologic remission (≤6 eosinophils per high-power field) and the change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score (range, 0 to 84, with higher values indicating more frequent or more severe dysphagia). RESULTS: In Part A, histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo (difference, 55 percentage points; 95% confidence interval [CI], 40 to 71; P<0.001). In Part B, histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo (difference between weekly dupilumab and placebo, 54 percentage points; 95% CI, 41 to 66 [P<0.001]; difference between dupilumab every 2 weeks and placebo, 56 percentage points; 95% CI, 43 to 69 [not significant per hierarchical testing]). The mean (±SD) DSQ scores at baseline were 33.6±12.41 in Part A and 36.7±11.22 in Part B; the scores improved with weekly dupilumab as compared with placebo, with differences of -12.32 (95% CI, -19.11 to -5.54) in Part A and -9.92 (95% CI, -14.81 to -5.02) in Part B (both P<0.001) but not with dupilumab every 2 weeks (difference in Part B, -0.51; 95% CI, -5.42 to 4.41). Serious adverse events occurred in 9 patients during the Part A or B treatment period (in 7 who received weekly dupilumab, 1 who received dupilumab every 2 weeks, and 1 who received placebo) and in 1 patient in the Part A-C group during the Part C treatment period who received placebo in Part A and weekly dupilumab in Part C. CONCLUSIONS: Among patients with eosinophilic esophagitis, subcutaneous dupilumab administered weekly improved histologic outcomes and alleviated symptoms of the disease. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03633617.).

Persistent esophageal changes after histologic remission in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is characterized by persistent or relapsing allergic inflammation, and both clinical and histologic features of esophageal inflammation persist over time in most individuals. Mechanisms contributing to EoE relapse are not understood, and chronic EoE-directed therapy is therefore required to prevent long-term sequelae. OBJECTIVE: We investigated whether EoE patients in histologic remission have persistent dysregulation of esophageal gene expression. METHODS: Esophageal biopsy samples from 51 pediatric and 52 adult subjects with EoE in histopathologic remission (<15 eosinophils per high-power field [eos/hpf]) and control (48 pediatric and 167 adult) subjects from multiple institutions were subjected to molecular profiling by the EoE diagnostic panel, which comprises a set of 94 esophageal transcripts differentially expressed in active EoE. RESULTS: Defining remission as <15 eos/hpf, we identified 51 and 32 differentially expressed genes in pediatric and adult EoE patients compared to control individuals, respectively (false discovery rate < 0.05). Using the stringent definition of remission (0 eos/hpf), the adult and pediatric cohorts continued to have 18 and 25 differentially expressed genes (false discovery rate < 0.05). Among 6 shared genes between adults and children, CDH26 was upregulated in both children and adults; immunohistochemistry demonstrated increased cadherin 26 staining in the epithelium of EoE patients in remission compared to non-EoE controls. In the adult cohort, POSTN expression correlated with the endoscopic reference system score (Spearman r = 0.35, P = .011), specifically correlating with the rings' endoscopic reference system subscore (r = 0.53, P = .004). CONCLUSION: We have identified persistent EoE-associated esophageal gene expression in patients with disease in deep remission. These data suggest potential inflammation-induced epigenetic mechanisms may influence gene expression during remission in EoE and provide insight into possible mechanisms that underlie relapse in EoE.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis.

BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis.

BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains. CONCLUSIONS: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.

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

BACKGROUND: A 6-food elimination diet in pediatric eosinophilic esophagitis (EoE) is difficult to implement and may negatively affect quality of life (QoL). Less restrictive elimination diets may balance QoL and efficacy. OBJECTIVE: We performed a multisite, 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. METHODS: Patients aged 6 to 17 years with histologically active and symptomatic EoE were randomized 1:1 to 1FED or 4FED for 12 weeks. Primary end point was symptom improvement by Pediatric Eosinophilic Esophagitis Symptom Score (PEESS). Secondary end points were proportion experiencing histologic remission (<15 eosinophils per high-power field); change in histologic features (histology scoring system), endoscopic severity (endoscopic reference score), transcriptome (EoE diagnostic panel), and QoL scores; and predictors of remission. RESULTS: Sixty-three patients were randomly assigned to 1FED (n = 38) and 4FED (n = 25). In 4FED versus 1FED, mean PEESS improved -25.0 versus -14.5 (P = .04), but remission rates (41% vs 44%; P = 1.00), histology scoring system (-0.25 vs -0.29; P = .77), endoscopic reference score (-1.10 vs -0.58; P = .47), and QoL scores were similar between groups. The EoE transcriptome normalized in those with histologic response to both diets. Baseline peak eosinophil count predicted remission (odds ratio, 0.975 [95% confidence interval, 0.953-0.999], P = .04; cutoff ≤42 eosinophils per high-power field). The 4FED withdrawal rate (32%) exceeded that of 1FED (11%) (P = .0496). CONCLUSIONS: Although 4FED moderately improved symptoms compared with 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.

Advances and ongoing challenges in eosinophilic gastrointestinal disorders presented at the CEGIR/TIGERs Symposium at the 2024 American Academy of Allergy, Asthma & Immunology meeting.

The Consortium of Eosinophilic Gastrointestinal disease Researchers (CEGIR) and The International Gastrointestinal Eosinophil Researchers (TIGERs) organized a daylong symposium at the 2024 annual meeting of the American Academy of Allergy, Asthma & Immunology. The symposium featured new discoveries in basic and translational research as well as debates on the mechanisms and management of eosinophilic gastrointestinal diseases. Updates on recent clinical trials and consensus guidelines were also presented. We summarize the updates on eosinophilic gastrointestinal diseases presented at the symposium.

Dupilumab demonstrated efficacy and was well tolerated regardless of prior use of swallowed topical corticosteroids in adolescent and adult patients with eosinophilic oesophagitis: a subgroup analysis of the phase 3 LIBERTY EoE TREET study.

OBJECTIVE: To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC. DESIGN: Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup. RESULTS: Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC. CONCLUSION: Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC. TRIAL REGISTRATION NUMBER: NCT03633617.

Real-World Efficacy of Dupilumab in Severe, Treatment-Refractory, and Fibrostenotic Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Dupilumab is approved for treatment of eosinophilic esophagitis (EoE), but real-world data are lacking. We aimed to determine the real-world efficacy of dupilumab in patients with severe, treatment-refractory, and fibrostenotic EoE. METHODS: We conducted a retrospective cohort study of EoE patients prescribed dupilumab and who were treatment-refractory to standard modalities. Patient demographics, clinical characteristics, EoE history, and procedural data (including the histologically worst, predupilumab, and postdupilumab endoscopies) were extracted from medical records. Symptomatic, endoscopic, and histologic responses were assessed for the worst and predupilumab endoscopies compared with the postdupilumab endoscopy. RESULTS: We identified 46 patients with refractory fibrostenotic EoE who were treated with dupilumab. Patients showed endoscopic, histologic, and symptomatic improvement on dupilumab compared with both the worst and the predupilumab esophagogastroduodenoscopies. The peak eosinophil counts decreased markedly, and postdupilumab histologic response rates were 80% and 57% for fewer than 15 eosinophils per high-power field and 6 or fewer eosinophils per high-power field, respectively, and the Endoscopic Reference Score decreased from 5.01 to 1.89 (P < .001 for all). Although the proportion of strictures was stable, there was a significant increase in the predilation esophageal diameter (from 13.9 to 16.0 mm; P < .001). Global symptom improvement was reported in 91% (P < .001). CONCLUSIONS: In this population of severe, refractory, and fibrostenotic EoE patients, most achieved histologic, endoscopic, and symptom improvement with a median of 6 months of dupilumab, and esophageal stricture diameter improved. Dupilumab has real-world efficacy for a severe EoE population, most of whom would not have qualified for prior clinical trials.

Prevalence and Costs of Esophageal Strictures in the United States.

BACKGROUND & AIMS: Esophageal strictures are a leading cause of dysphagia, but data regarding the epidemiology of esophageal strictures are limited. This study aimed to investigate the prevalence, health care utilization, and financial burden of esophageal strictures in the United States. METHODS: We performed a retrospective cohort study using 2 large national insurance claims databases (MarketScan and Medicare). Using International Classification of Diseases-9 and -10 diagnostic codes, annual prevalence was calculated for both cohorts overall, and stratified by age and sex strata. Most common diagnostic and procedural codes associated with esophageal strictures were extracted and analyzed to estimate health care utilization. Direct annual medical costs of esophageal strictures were calculated. RESULTS: The annual prevalence of esophageal strictures in MarketScan in 2021 was 203.14 cases/100,000 people, whereas the annual prevalence in Medicare cohort in 2017 was 1123.47 cases/100,000. Although rates were relatively stable over time, esophageal stricture prevalence increased with advancing age. No prevalence differences were noticed between males and females. Gastroesophageal reflux disease/erosive esophagitis was the top diagnostic code associated with esophageal strictures, although an increase in the proportion of eosinophilic esophagitis codes was noted over time. Esophageal dilation codes were present in ∼50% of stricture cases. The total health care costs associated with esophageal strictures were estimated at $1.39 billion in 2017. CONCLUSIONS: Esophageal strictures are common, affecting between 1/100 and 1/1000 patients in the United States, with the highest rates seen in patients aged 75 years and older. Accordingly, strictures have a significant financial burden on the health care system, with costs greater than $1 billion annually.

The Index of Severity for Eosinophilic Esophagitis (I-SEE) Reflects Longitudinal Clinicopathologic Changes in Children.

BACKGROUND AND AIMS: The Index of Severity for Eosinophilic Esophagitis (I-SEE) was recently developed. We aimed to understand I-SEE scores in a longitudinal pediatric cohort and to determine the relationship between I-SEE and clinical features in children. METHODS: We performed a retrospective analysis on a prospectively enrolled cohort of children at a single center who were treated as part of routine clinical care. I-SEE was calculated at the diagnostic and follow-up endoscopies over a mean of 6.6 years. Scoring was 0 for inactive, 1-6 for mild, 7-14 for moderate, and ≥15 for severe eosinophilic esophagitis (EoE). We analyzed clinical, endoscopic, and histologic features at each instance. Symptoms were analyzed at the baseline, first follow-up, and last endoscopic instance. RESULTS: Of 67 children who met study criteria of at least 3 endoscopies over at least 2 years of follow-up time, 43%, 36%, and 21% had mild, moderate, and severe I-SEE scores at baseline, respectively. Between the first and second endoscopic instances, there was a decrease in the group mean I-SEE from 9.7 ± 7.2 to 6.1 ± 5.9 (P < .001). By the last instance, the overall I-SEE score dropped to 3.9 (P < .001). Body mass index <5% and poor feeding were more common in the children with severe I-SEE scores at baseline, and both improved by the last instance. Fibrosis was improved by the last instance biopsy (P < .01). CONCLUSIONS: I-SEE is a responsive severity metric in children treated long term during routine clinical care. Baseline low body mass index and poor feeding were more common in children with severe I-SEE scores.

The Natural History of Eosinophilic Gastrointestinal Diseases Is Influenced by Age of Onset and Location of Involvement.

INTRODUCTION: It is unknown whether concomitant esophageal involvement or anatomic location of eosinophilic infiltration affects the natural history of eosinophilic gastrointestinal disease (EGID). METHODS: A retrospective cohort study was performed using the University of North Carolina EGID Clinicopathologic Database. Patients were adults and children with a prior EGID diagnosis based on clinicopathologic features. Demographics, clinical characteristics, treatment information, and procedural data were extracted from medical records. Clinical course and flare history were characterized. RESULTS: Among 97 patients, 43% had EGID + esophageal involvement and 57% had EGID only. Patients with esophageal involvement had a longer diagnostic delay preceding diagnosis (36.6 vs 11.6 months, P = 0.001), more dysphagia (50% vs 18%; P = 0.001), required more chronic therapy (77% vs 52%, P = 0.016), and exhibited more progressive disease (25% vs 6%, P = 0.027). A continuous disease course was most common in eosinophilic gastritis (78%) while patients with eosinophilic gastritis + eosinophilic enteritis (29%) and eosinophilic enteritis + eosinophilic colitis (50%) had the highest proportion of progressive and relapsing disease, respectively ( P = 0.045). A continuous disease course occurred more frequently in children (71%, P = 0.03) and those with single organ involvement (65%), whereas adults had more relapsing (39%) or progressive disease (18%). DISCUSSION: EGIDs with and without esophageal involvement display many similarities, although patients with esophageal involvement more frequently had dysphagia, had progressive disease courses, and required more chronic therapy. Location of involvement and age of onset affected the natural history with higher proportions of relapsing or progressive disease seen in adults and patients with small bowel or multiorgan involvement while a continuous disease course was more common in children and patients with gastric-only involvement.

Health State Utility is Substantially Reduced With an Increasing Burden of Patient-Reported Symptoms in Eosinophilic Esophagitis.

INTRODUCTION: We aimed to estimate health state utility in eosinophilic esophagitis (EoE) by histologic activity and assess association with disease parameters. METHODS: In this cross-sectional study, we measured health state utility by time trade-off and assessed symptoms with the EoE Symptom Activity Index. RESULTS: In 51 adults with EoE, the mean utility was 0.91 (95% CI 0.86, 0.95). Utility was numerically worse in patients with dilation or a smaller stricture diameter. With each ten-point improvement in EoE Symptom Activity Index, utility increased by 0.03 (95% CI 0.01, 0.05). DISCUSSION: EoE is associated with reduced health state utility, with symptoms most strongly predicting valuation.

Healthcare Resource Utilization and Costs Associated With Eosinophilic Esophagitis Among Commercially Insured Patients in the United States.

INTRODUCTION: To evaluate real-world healthcare resource utilization (HCRU) and costs associated with eosinophilic esophagitis (EoE) in the United States. METHODS: Retrospective case-control cohort analysis of Optum Clinformatics claims data (January 2008-September 2020) comparing unadjusted and adjusted HCRU (visits per 1,000 patients per month) and all-cause costs (per patient per month). RESULTS: Patients with EoE incurred significantly higher monthly HCRU (adjusted Δ [95% confidence interval]: inpatient visits, 2.8 [0.1-4.0]; emergency department visits, 14.7 [4.3-32.1]; outpatient visits, 388.8 [362.1-418.0]); and costs ($581 [$421-$600]) vs matched controls (all P < 0.001). DISCUSSION: EoE imposes substantial economic burden. More effective and targeted treatments that improve outcomes for patients are needed.

Dupilumab Improves Health-Related Quality of Life and a Range of Symptoms in Patients With Eosinophilic Esophagitis.

INTRODUCTION: Improvements in symptomatic experience and health-related quality of life (HRQoL) are among the most important treatment benefits in patients with eosinophilic esophagitis (EoE). We assessed the impact of dupilumab treatment on HRQoL, patients' impression of dysphagia, and symptoms beyond dysphagia in adults/adolescents (≥12 years) with EoE in parts A and B of the LIBERTY EoE TREET (NCT03633617) study. METHODS: The EoE Symptom Questionnaire (EoE-SQ; frequency and severity of nondysphagia symptoms), EoE Impact Questionnaire (impact of EoE on HRQoL), and Patient Global Impression of Severity and Patient Global Impression of Change of dysphagia were used to assess the efficacy of weekly dupilumab 300 mg vs placebo. RESULTS: At week 24, dupilumab reduced EoE-SQ Frequency (least squares mean difference vs placebo [95% confidence interval] part A -1.7 [-2.9, -0.5], part B -1.4 [-2.3, -0.5]; both P < 0.01) and EoE-SQ Severity (part A -2.0 [-3.9, 0.0], P < 0.05, part B -1.5 [-3.0, 0.1], P = 0.07) overall scores, and improved scores across all individual items. Improvement in the dupilumab group was clinically meaningful to patients. Dupilumab also meaningfully improved EoE Impact Questionnaire average scores and improved individual item scores at week 24, particularly emotional and sleep disturbance. More dupilumab-treated patients reported improvement in the Patient Global Impression of Change of dysphagia vs placebo or reported having no symptoms per the Patient Global Impression of Severity of dysphagia at week 24. DISCUSSION: Dupilumab reduced the impact of EoE on multiple aspects of HRQoL, patients' impression of dysphagia, and frequency and severity of symptoms beyond dysphagia in adults/adolescents with EoE.

Treatment preference archetypes in eosinophilic esophagitis and their implications for therapy.

BACKGROUND: Little is known about how patients make decisions about and prioritize, therapies and disease management in eosinophilic esophagitis (EoE). We aimed to systematically identify and characterize patient perspectives and attitudes that influence decision making for EoE management. METHODS: To understand the diverse attitudes and values of EoE patients, we designed a study using the Q-method. We iteratively developed 31 statements related to EoE disease management. Participants sorted statements by ranking from +4 (most agree) to -4 (most disagree). By-person factor analysis, using 2- and 3- factor rotation, revealed distinct preference archetypes. RESULTS: Thirty-four adults with EoE (mean age 40.9, 51.4% male, 82.9% White) were recruited from gastroenterology and allergy clinics from a single center. We identified two treatment-centered archetypes: Medication preference, driven by symptoms and the desire to minimize risk of complications, and Natural treatment preference, focusing on identifying trigger foods and diet adherence. Three-factor analysis revealed an additional archetype: Treatment ambivalent, a view of EoE as a mild and episodic (not chronic) disease with low priority to treat. Comparison by factor revealed 54% of those in the natural preference archetype were recategorized as treatment ambivalent, suggesting that they see natural treatment as a less complicated or milder strategy and may be at risk of nonadherence and reduced treatment uptake. CONCLUSIONS: We identified three distinct treatment preference archetypes among individuals with EoE, underscoring the need for personalized treatment strategies, especially for those favoring natural approaches but masking ambivalence, and may be at risk for nonadherence or loss to follow-up.

Clinical Features and Treatment Response to Topical Steroids in Ethnic and Racial Minority Patients With Eosinophilic Esophagitis.

INTRODUCTION: Differences in eosinophilic esophagitis (EoE) presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. METHODS: This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic response. Hispanic EoE patients were compared with non-Hispanics at baseline and before and after treatment. The same analyses were repeated for White vs non-Whites. RESULTS: Of 1,026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis and had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; P = 0.01), and odds of histologic response remained lower after controlling for potential confounders (adjusted odds ratio 0.40, 95% confidence intervals: 0.19-0.87). DISCUSSION: Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS.

Association between time from esophageal food impaction to endoscopy and adverse events.

BACKGROUND AND AIMS: Guidelines recommend emergent or urgent EGD for esophageal food impaction (EFI), but data on how time to EGD impacts the risk of adverse events remain limited. We determined whether EFI-to-EGD time was associated with adverse events. METHODS: In this retrospective cohort study of patients with endoscopically confirmed EFI, adverse events were classified as esophageal (mucosal tear, bleeding, perforation) or extraesophageal (aspiration, respiratory compromise, hypotension, arrhythmia). Esophageal perforation and extraesophageal adverse events requiring intensive care unit admission were classified as serious adverse events. Baseline characteristics, event details, and procedural details were compared between patients with and without adverse events. Multivariable logistic regression was performed to assess for an association between EFI-to-EGD time and adverse events. RESULTS: Of 188 patients with EFI, 22 (12%) had any adverse event and 2 (1%) had a serious adverse event. Patients with adverse events were older and more likely to have an esophageal motility disorder, to tolerate secretions at presentation, and to have a higher American Society of Anesthesiologists score. EFI-to-EGD time was similar in those with and without adverse events. On multivariable analysis, EFI-to-EGD time was not associated with adverse events (odds ratio, 1.00 [95% confidence interval, .97-1.04] for 1-hour increments; odds ratio, 1.03 [95% confidence interval, .86-1.24] for 6-hour increments). Results were similar after stratifying by eosinophilic esophagitis status and after adjusting for possible confounders. CONCLUSIONS: Because the time from EFI to EGD is not associated with adverse events, emergent EGD for EFI may be unnecessary, and other considerations may determine EGD timing.

Topical Steroids Are Effective and Safe in Patients With Eosinophilic Esophagitis Over a Median of 6.5 Years of Chronic Use.

GOALS: To determine long-term efficacy and safety of tCS for treatment of EoE. BACKGROUND: Maintenance therapy with topical corticosteroids (tCS) is recommended for eosinophilic esophagitis (EoE), but data for long-term use are still needed. STUDY: This retrospective cohort study assessed newly diagnosed patients with EoE who were treated with a tCS and had a follow-up endoscopy with biopsy after at least 5 years. Histologic symptomatic and endoscopic responses were extracted from medical records. Patients who did and did not have long-term tCS treatment were compared at baseline, and outcomes for patients were assessed at their last endoscopy while on tCS. RESULTS: Of 431 patients with EoE treated with tCS, 104 met inclusion criteria for long-term use. For patients with long-term tCS use, the median time (IQR) on tCS was 6.5 years (5.4 to 8.8 y). At the last endoscopy, 54% had histologic response (<15 eos/hpf), but those with excellent adherence had a histologic response of 64%. Endoscopic severity also decreased with improved adherence which was strongly associated with EREFS (1.7 vs. 2.8 vs. 4.0 for excellent, good, and poor adherence; P<0.001). Symptomatic response was 68% overall, but only 40% in those with poor adherence (P=0.07). Complications of taking tCS were uncommon (adrenal insufficiency: 1%; osteopenia: 1%; and esophageal candidiasis: 4% at final endoscopy). CONCLUSIONS: Long-term tCS (median 6.5 y) were generally effective, especially with better adherence, and also safe, with only rare serious complications. These data can be used to help patients make clinical decisions about chronic tCS use in EoE.