Prevalence and costs of eosinophilic esophagitis in the United States.

BACKGROUND AND AIMS: Eosinophilic esophagitis (EoE) has been continually increasing in prevalence but current estimates are lacking. We aimed to determine updated estimates of the prevalence and medical costs associated with EoE in the United States. METHODS: We used two large administrative databases, MarketScan and Medicare, and International Classification of Disease codes to calculate annual prevalence of EoE, as well as age- and sex- stratified estimates, standardized to the U.S. POPULATION: Health care utilization, including medications and endoscopic procedures was quantified, and annual EoE-associated costs were estimated. RESULTS: We identified 20,435 EoE cases in MarketScan in 2022 and 1,913 EoE cases in Medicare in 2017. This translated to prevalences of 163.08 cases/100,000 and 64.83 cases/ 100,000 in MarketScan and Medicare, respectively. There was a 5-fold increase in prevalence in both databases since 2009. In MarketScan, prevalence was higher among males (204.45/100,000 vs 122.06/100,000 among females); for both sexes, peak prevalence was from 40-44years. Standardized to the U.S. population, the prevalence of EoE was 142.5/100,000, extrapolating to 472,380 cases. Total EoE-associated healthcare costs were estimated to be $1.32 billion in 2024 dollars after accounting for inflation. CONCLUSIONS: The prevalence of EoE continues to increase, with a rate of 1 in 617 in 2022 in those <65 years of age, and 1 in 1562 in 2017 those ≥65 years. Standardized to the U.S. population, the overall prevalence was approximately 1 in 700. EoE-associated annual costs were estimated to be $1.3 billion in 2024 dollars, representing a substantial financial burden.

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.

Impact of cannabis use on presentation and treatment response in eosinophilic esophagitis.

Cannabis use is becoming increasingly common, both for recreational and medical purposes. However, there is a paucity of data regarding cannabis use in the context of eosinophilic esophagitis (EoE). We aimed to determine the impact of cannabis use on presentation and treatment response in EoE. To this end, we conducted a retrospective cohort study at a large academic medical center of newly diagnosed EoE patients age ≥ 12 years. Self-reported cannabis use status, baseline characteristics, and treatment response to topical corticosteroids and dietary therapy data were extracted. Bivariate and multivariable analyses were used to compare cannabis users and non-users at time of EoE diagnosis and to assess treatment response. Of 983 EoE patients, 80 reported using cannabis, with the majority reporting daily use and administration by inhalation. Baseline symptoms and peak eosinophil count were similar between cannabis users and non-users; cannabis users were less likely to have baseline endoscopic findings of exudates, edema, and stricture, and lower total Endoscopic Reference Score. On multivariable analysis, younger age, male sex, non-White race, and psychiatric diagnosis were independently associated with history of cannabis use at EoE presentation and stricture was independently associated with cannabis non-use. Post-treatment symptom and histologic responses were similar between cannabis users and non-users though there was a higher odds of post-treatment endoscopic inflammatory features with cannabis use. In conclusion, despite presenting with milder initial endoscopic findings, cannabis users exhibited greater inflammatory findings after treatment, highlighting a potential negative influence of cannabis use on EoE management.

Design of a phase 3, randomized, double-blind, placebo-controlled, 48-week study to evaluate the efficacy and safety of cendakimab in adult and adolescent patients with eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory condition that interferes with normal food ingestion, negatively impacting quality of life (QoL). Treatment options include proton pump inhibitors, corticosteroids, biologics, or dietary elimination; however, ∼1/3 of patients remain insufficiently controlled. The pathogenesis of EoE involves interleukin-13 (IL-13); therefore, targeted IL-13 inhibition may be beneficial. In a phase 2 study, cendakimab, a recombinant, humanized anti-IL-13 monoclonal antibody, significantly reduced mean esophageal eosinophil counts and improved other inflammatory parameters in patients with EoE. These findings prompted further investigation of the efficacy and safety of cendakimab in adults and adolescents with EoE in a phase 3 registrational study (NCT04753697), the design of which is presented here. METHODS: This multicenter, multinational, randomized, double-blind, placebo-controlled, 48-week, treat-through study plans to enroll 399 adults and adolescents. Randomized patients (1:1:1) will receive subcutaneous administration of 1) cendakimab 360 mg once weekly (QW) for 48 weeks, 2) cendakimab 360 mg QW for 24 weeks followed by cendakimab 360 mg every other week (with matching placebo on alternative weeks to maintain the blind) for 24 weeks, or 3) placebo QW for 48 weeks. Co-primary endpoints are mean change from baseline in dysphagia days and proportion of patients with eosinophil histologic response, defined as peak esophageal eosinophil count ≤6 per high-power field, at 24 weeks. Secondary and exploratory endpoints will address endoscopic and histologic features, QoL, safety, and pharmacokinetic assessments. CONCLUSION: This phase 3 pivotal study will determine whether cendakimab provides an effective, safe, targeted treatment for patients 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.

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.

Psychometric evaluation of the Dysphagia Symptom Questionnaire for adults and adolescents with eosinophilic esophagitis.

Background: Eosinophilic esophagitis (EoE) is a chronic, inflammatory disease of the esophagus leading to symptoms of esophageal dysfunction; dysphagia is the most common symptom experienced by adults and adolescents. Objective: We sought to perform a psychometric evaluation of the Dysphagia Symptom Questionnaire (DSQ), a patient-reported outcome measure for patients with EoE. Methods: Using baseline and week 24 data from the randomized, interventional, multinational phase 3 R668-EE-1774 trial (NCT03633617), the measurement properties of the DSQ-including reliability, construct and known-groups validity, responsiveness, and interpretation of change-were evaluated. Results: The analysis population comprised 239 patients with EoE (age [mean ± SD], 28.1 ± 13.14 years; 63.6% male; 90.4% White). Intraclass correlation coefficients of 0.92 and 0.97 exceeded the acceptable reliability threshold (≥0.70). Construct validity correlations with EoE symptom and impact measures were moderate at baseline (|r| = 0.44-0.55) and week 24 (|r| = 0.55-0.69), and the DSQ biweekly total score discriminated among groups defined by disease severity. Analyses exploring interpretation of change from baseline on the DSQ biweekly total score indicated thresholds for within-patient improvement ranging from 9 to 23 points; a within-patient improvement from baseline of 13 points or greater could be considered clinically meaningful. Conclusions: This analysis confirmed that the DSQ has acceptable distributional properties, test-retest reliability, construct validity, and ability to detect change. Therefore, the DSQ is a valid and reliable measure to assess the patient-reported symptom of dysphagia among adult and adolescent patients with EoE in the context of a clinical trial setting.

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.

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.

Performing Esophageal Biopsies Is Safe During Upper Endoscopy for Food Impaction but Are Underperformed in Certain Populations.

BACKGROUND: Despite recommendations to perform esophageal biopsies during esophagogastroduodenoscopy (EGD) for esophageal food impaction to evaluate for eosinophilic esophagitis (EoE), endoscopists often forgo biopsies. There are minimal data on the risks of biopsies in this setting. AIMS: To determine the safety of performing biopsies during EGD for food impaction. METHODS: We conducted a retrospective cohort study of patients who presented to University of North Carolina Hospitals from 2014 to 2021 with endoscopically confirmed food impaction. Data were abstracted from the medical records. Baseline clinical characteristics, procedural details, and adverse events were compared between patients who did and did not undergo biopsy. Adverse events were classified as esophageal (mucosal tear, bleeding, perforation) or extra-esophageal (aspiration, respiratory compromise, hypotension, arrhythmia). RESULTS: Of 188 patients who underwent EGD for food impaction, 73 (39%) had biopsies taken. Older and non-White patients were less likely to be biopsied. None of the Black patients had biopsies taken. Only 2 (2.7%) of the 73 biopsied patients had an adverse event, and neither was related to the biopsies. Patients who were biopsied were less likely to experience adverse events. There were no differences in re-admission, ICU admission, or 30-day mortality between patients who were and were not biopsied. CONCLUSIONS: Esophageal biopsies remain underperformed during EGD for food impaction, especially in certain patient populations. Esophageal biopsies at the time of food impaction are unlikely to cause adverse events. Safety concerns should not preclude biopsies, and biopsies should be performed in the absence of extenuating circumstances.

A clinical predictive model identifies pediatric patients at risk for eosinophilic esophagitis.

BACKGROUND: Identifying children needing endoscopic evaluation for suspected eosinophilic esophagitis (EoE) is crucial for prompt diagnosis and management. AIMS: We aimed to develop a clinical prediction tool to distinguish children with EoE from children without the disease before endoscopy. METHODS: We conducted a retrospective case-control study of children undergoing upper endoscopy at a tertiary care center. Clinical characteristics before endoscopy were extracted from 380 EoE cases and 380 controls without EoE. We built a predictive model for case-control status and performed age-stratified analyses. RESULTS: After multivariable analysis, history of adaptive eating behaviors, food allergy, food impaction, male sex, and regurgitation were independently associated with EoE, and abdominal pain and failure to thrive with control status (AUC 0.81). Food allergy and male sex were predictors of EoE across all ages. Regurgitation and adaptive eating behaviors were specific to EoE in early (0-5 years) (AUC 0.74) and middle childhood (6-11 years) (AUC 0.82), while dysphagia and food impaction were specific to EoE in the adolescence (12-17 years) (AUC 0.87). CONCLUSION: We determined age-specific clinical features that predict EoE with good discrimination in a pediatric population before endoscopy. Validation of this model in an independent population can confirm the utility of this tool.

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.

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.

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 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.