S832 Dupilumab Normalizes Histopathologic Features in Adults and Adolescents With Eosinophilic Esophagitis: Post Hoc Analysis of the Phase 3 LIBERTY EoE TREET Study

Introduction: The diagnosis of eosinophilic esophagitis (EoE) relies on symptoms of esophageal dysfunction and esophageal eosinophil density >15 eosinophils/high-power field. The EoE Histologic Scoring System (EoEHSS) provides a comprehensive assessment of 8 histopathologic features commonly seen in EoE patients. Here, we assessed the proportion of adolescents and adults with EoE who resolved each individual EoEHSS feature with dupilumab vs placebo in LIBERTY EoE TREET (NCT03633617). Methods: In Part B, patients aged ≥12 years with EoE were randomized 1:1 to 24 weeks of dupilumab 300 mg weekly or placebo. Eligible patients entered Part C and received dupilumab 300 mg weekly to week 52. EoEHSS component (esophageal inflammation [EI], eosinophil abscesses [EA], eosinophil surface layering [ESL], surface epithelial alteration [SEA], basal zone hyperplasia [BZH], dilated intercellular spaces [DIS], dyskeratotic epithelial cells [DEC], and lamina propria fibrosis [LPF]) scores were evaluated at baseline, week 24, and week 52. The proportion of patients who achieved a score of 0 (resolution) for each EoEHSS grade and stage component was assessed. Results: The proportions of patients with EoEHSS grade/stage component scores of 0 at baseline were similar in the dupilumab vs placebo groups: EA (31% vs 32%/31% vs 32%), ESL (14% vs 23%/14% vs 23%), SEA (35% vs 42%/35% vs 42%), BZH (0% vs 4%/0% vs 4%), LPF (36% vs 37%/36% vs 37%), DEC (73% vs 84%/73% vs 84%); no patients had EI or DIS grade/stage scores of 0. Dupilumab treatment vs placebo led to a greater proportion of patients achieving resolution in both grade/stage EA (97% vs 49%/97% vs 49%), ESL (96% vs 30%/96% vs 30%), SEA (87% vs 50%/87% vs 50%), BZH (78% vs 11%/78% vs 11%), LPF (90% vs 35%/90% vs 35%) (all P < 0.0001), EI (15% vs 0%/88% vs 8%; P < 0.001), and DEC (93% vs 74%/93% vs 74%; P < 0.01) at week 24. Resolution was not observed in DIS (0% vs 2.8%; P = 0.2415). At week 52, effects were maintained or improved further with continued dupilumab; improvements in most EoEHSS components were observed in patients who switched from placebo to dupilumab at week 24. Conclusion: Dupilumab led to resolution of both grade and stage scores in most EoEHSS histopathologic features vs placebo after 24 weeks of treatment; resolution was maintained or achieved in patients receiving continuous dupilumab for 52 weeks. The greatest improvements occurred in eosinophil- (ESL) and epithelial-related (DEC and BZH) features, and LPF.