P4880 - Endoscopic Severity, Unlike Histology, Is Associated With Increasing Age in EoE Pediatric, Adolescent, and Adult Patients at Baseline: Pooled Post-Hoc Analysis of Phase 3 KIDS and TREET Clinical Trials

Noam Zevit, MD, MPH¹, Evan S. Dellon, MD, MPH², Mirna Chehade, MD, MPH³, Eric E. Low, MD, MPH⁴, Seema Aceves, MD, PhD⁵, Gary Falk, MD, MS⁶, Gaia Pellegatta, MD⁷, Carlos Gonzalez, MS⁸, Sherif Zaghloul, MD, MSc⁹, Bram P. Raphael, MD⁸, James T. Angello, PharmD⁹, Amr Radwan, MBBCh, MA⁸
1Institute of Gastroenterology, Nutrition, and Liver Diseases, Schneider Children’s Medical Center, Petah Tikva, and Gray Faculty of Medical Sciences, Tel-Aviv University, Tel Aviv, Tel Aviv, Israel; 2Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC; 3Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, New York, NY; 4Jennifer Moreno Veteran Affairs San Diego Healthcare System, University of California, San Diego, CA; 5Division of Allergy Immunology, Departments of Pediatrics and Medicine, University of California and Rady Children's Hospital, San Diego, CA; 6Division of Gastroenterology and Hepatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; 7Digestive Endoscopy Unit, Division of Gastroenterology, IRCCS Humanitas Research Hospital, Milan, Lombardia, Italy; 8Regeneron Pharmaceuticals Inc., Tarrytown, NY; 9Sanofi, Morristown, NJ

Introduction: Eosinophilic esophagitis (EoE) is a type 2 inflammatory disease affecting the esophagus in all ages. Features of EoE improved significantly following dupilumab treatment, an antibody blocking interleukin-4 and -13, confirming common pathophysiology across ages. Research suggests disease severity may differ by age. To assess this, we investigated associations between age and disease characteristics using combined data from 2 phase 3 trials.

Methods: This is a post-hoc analysis from the EoE KIDS (NCT04394351) and LIBERTY EoE TREET (NCT03633617) trials. Non-age-based inclusion/exclusion criteria were similar, apart from a minimum dysphagia requirement in TREET, not required in KIDS. Patient demographics, prior treatments, and EoE disease characteristics were assessed in 3 subgroups: pediatric (≥1–< 12 years); adolescent (≥12–< 18 years); adult (≥18 years). Regression analyses using age as a continuous variable evaluated the impact of a 1-year increase in age on each variable. Parameter estimate size indicated the strength of the relationship; positive/negative indicated the direction of the association.

Results: Younger age was associated with greater likelihood of male sex (parameter estimate: −0.024 [95% confidence interval: −0.037 to −0.010]; P< 0.001), having ≥1 concurrent type 2 inflammatory disease (−0.043 [−0.060 to −0.025]; P< 0.0001), and having a food elimination diet (−0.040 [−0.054 to −0.026]; P< 0.0001; Table). Endoscopic severity, as assessed by EREFS total score, increased with age (0.016 [0.006–0.026]; P< 0.01), but the relationship was not consistent across fibrostenotic and inflammatory subscores. Inflammatory features edema and exudates decreased with increasing age (-0.004 [-0.006, -0.002]; P< 0.001, -0.008 [-0.006, -0.002] P<0.001, respectively), and fibrostenotic features rings and stricture increased with increasing age (0.023 [0.019, 0.028]; P< 0.0001, 0.008 [0.005, 0.010] P< 0.0001). The likelihood of having a prior history of esophageal dilation also increased with increasing age (0.078 [0.060–0.095]; P< 0.0001). Histologic features were not significantly associated with age.

Discussion: In this pooled analysis of EoE KIDS and LIBERTY EoE TREET, associations between age and clinical/disease-related characteristics of EoE were observed. While baseline histologic features were similar across all ages, fibrostenotic endoscopic features and prior esophageal dilations were more common with increasing age, with inflammatory features more common in younger patients.


Figure: Table. Association between patient age and baseline patient demographics and characteristics in the EoE KIDS and LIBERTY EoE TREET studies.
Data are mean (SD), unless otherwise stated.
All P-values are nominal *P <0.01, ***P <0.001, ****P <0.0001.
† Regression analysis using age as a continuous variable. Linear regression was performed when the row variable (responder) was continuous, while a logistic regression was performed when the row variable was categorical. For categorical variables coded as “Yes” vs. “No,” “No” was set as the reference. If a categorical variable included “Yes,” “No,” and “Missing,” observations with “Missing” were excluded from the model. For gender (Male vs. Female), “Female” was set as the reference. For type 2 inflammatory disease (With vs. Without) “Without” was set as the reference in each individual type 2 item. Age was included in the model as a covariate.
‡ The EoE-HSS assessed the grade (extent) and stage (severity) of 8 histologic features of EoE: eosinophil surface layering, eosinophil abscesses, basal zone hyperplasia, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis.
§ Worst-observed scores (higher scores indicating greater severity) were determined based on endoscopy findings from the worst observed proximal or distal esophageal regions. Worst observed total EREFS score is defined as sum of worst edema, rings, exudates, furrows, and stricture (range 0–9). Worst observed inflammatory score is defined as the sum of the worst Edema, Exudates, and Furrows scores if the worst Edema is Present, or the worst Exudates is Mild or Severe, or the worst Furrows is Mild. Worst observed fibrostenotic score is defined as the sum of the worst Rings and Stricture scores if the worst Rings is Mild or Moderate, or the worst Stricture is Present.
CI, confidence interval; EoE, eosinophilic esophagitis; EREFS, EoE Endoscopic Reference Score; hpf, high-powered field; HSS, histologic stage score; SD, standard deviation; STC, swallowed topical corticosteroids.

Disclosures:
Noam Zevit: Adare Pharmaceuticals – Advisory Committee/Board Member, Consultant. AstraZeneca – Advisory Committee/Board Member, Consultant. Dr Falk Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Rafa Inc. – Advisory Committee/Board Member, Consultant, Speakers Bureau. Regeneron Pharmaceuticals Inc. – Advisory Committee/Board Member, Consultant, Speakers Bureau. Rome Foundation – Honoraria. Sanofi – Advisory Committee/Board Member, Consultant, Speakers Bureau. Takeda – Advisory Committee/Board Member, Consultant.
Evan Dellon: AbbVie – Consultant. Adare/Ellodi – Consultant, Grant/Research Support. Akesobio – Consultant. Alfasigma – Consultant. ALK – Consultant. Allakos – Consultant, Grant/Research Support. Amgen – Consultant. Apogee – Consultant. Apollo – Consultant. Aqilion – Consultant, Grant/Research Support. Arena/Pfizer – Consultant, Grant/Research Support. Aslan – Consultant. AstraZeneca – Consultant, Grant/Research Support. Avir – Consultant. Biocryst – Consultant. Bryn – Consultant. Calypso – Consultant. Celgene/Receptos/Bristol Myers Squibb – Consultant, Grant/Research Support. Celldex – Consultant, Grant/Research Support. Dr. Falk Pharma – Consultant. EsoCap – Consultant. Eupraxia – Consultant, Grant/Research Support. Ferring – Consultant, Grant/Research Support. GI Reviewers – Consultant. GSK – Consultant, Grant/Research Support. Holoclara – Consultant, Grant/Research Support. Invea – Consultant, Grant/Research Support. Knightpoint – Consultant. LucidDx – Consultant. Meritage – Grant/Research Support. Miraca – Grant/Research Support. Morphic – Consultant. Nexstone Immunology/Uniquity – Consultant. Nutricia – Consultant, Grant/Research Support. Parexel/Calyx – Consultant. Phathom – Consultant. Regeneron Pharmaceuticals Inc. – Consultant, Grant/Research Support. Revolo – Consultant, Grant/Research Support. Robarts/Alimentiv – Consultant. Sanofi – Consultant, Grant/Research Support. Shire/Takeda – Consultant, Grant/Research Support. Target RWE – Consultant. Third Harmonic Bio – Consultant. Uniquity – Grant/Research Support. Upstream Bio – Consultant.
Mirna Chehade: Adare Pharma Solutions/Ellodi Pharmaceuticals – Consultant, Grant/Research Support. Allakos – Consultant, Grant/Research Support. AstraZeneca – Consultant, Grant/Research Support. Bristol Myers Squibb – Consultant. Celgene – Grant/Research Support. Danone – Grant/Research Support. Nexstone Immunology/Uniquity Bio – Consultant. Phathom Pharmaceuticals – Consultant. Recludix Pharma – Consultant. Regeneron Pharmaceuticals Inc. – Consultant, Grant/Research Support. Sanofi – Consultant. Shire/Takeda – Consultant, Grant/Research Support.
Eric E. Low indicated no relevant financial relationships.
Seema Aceves: Aimmune – Advisory Committee/Board Member, Consultant. AstraZeneca – Advisory Committee/Board Member, Consultant. Medscape – Advisory Committee/Board Member, Consultant. Regeneron Pharmaceuticals Inc. – Speakers Bureau. Sanofi – Speakers Bureau. Shire-Takeda – Intellectual Property/Patents, Co-inventor of oral viscous budesonide, patented by the University of California, San Diego and licensed by Shire-Takeda..
Gary Falk indicated no relevant financial relationships.
Gaia Pellegatta: Dr Falk Pharma – Speakers Bureau. Sanofi – Advisory Committee/Board Member, Speakers Bureau.
Carlos Gonzalez: Regeneron Pharmaceuticals Inc. – Employee, Stock-publicly held company(excluding mutual/index funds).
Sherif Zaghloul: Sanofi – Employee, Stock Options.
Bram Raphael: Regeneron Pharmaceuticals Inc. – Employee, Stock-publicly held company(excluding mutual/index funds).
James Angello: Sanofi – Employee, Stock Options.
Amr Radwan: Regeneron Pharmaceuticals Inc. – Employee, Stock-publicly held company(excluding mutual/index funds).

Noam Zevit, MD, MPH¹, Evan S. Dellon, MD, MPH², Mirna Chehade, MD, MPH³, Eric E. Low, MD, MPH⁴, Seema Aceves, MD, PhD⁵, Gary Falk, MD, MS⁶, Gaia Pellegatta, MD⁷, Carlos Gonzalez, MS⁸, Sherif Zaghloul, MD, MSc⁹, Bram P. Raphael, MD⁸, James T. Angello, PharmD⁹, Amr Radwan, MBBCh, MA⁸. P4880 - Endoscopic Severity, Unlike Histology, Is Associated With Increasing Age in EoE Pediatric, Adolescent, and Adult Patients at Baseline: Pooled Post-Hoc Analysis of Phase 3 KIDS and TREET Clinical Trials, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.