D3.403 - Dupilumab improves multiple histopathologic features of eosinophilic esophagitis over 52 weeks: Post hoc analysis of the phase 3 LIBERTY EoE TREET study

Eosinophilic esophagitis (EoE) is characterized by eosinophil infiltration and histopathologic alterations to the esophageal mucosa. The validated EoE Histologic Scoring System (HSS) evaluates the severity/extent (grade/stage) of 8 histopathologic features of EoE. In LIBERTY EoE TREET (NCT03633617), dupilumab treatment resulted in absolute reductions from baseline in EoEHSS grade/stage vs placebo at Week (W) 24 and W52. Here, we assessed the long-term relative change in EoEHSS outcomes.

Patients with EoE aged ≥12 years were randomized 1:1 to 24 weeks of dupilumab 300 mg weekly (qw) or placebo in Part B of LIBERTY EoE TREET. Eligible patients who completed Part B entered Part C and received dupilumab 300 mg qw to W52. Percentage change from Part B baseline in EoEHSS grade/stage total, inflammatory (eosinophil inflammation [EI], eosinophil abscesses [EA], eosinophil surface layering [ESL], surface epithelial alteration [SEA]), architectural (basal zone hyperplasia [BZH], dilated intercellular spaces [DIS], dyskeratotic epithelial cells [DEC], lamina propria fibrosis [LPF]), and component scores at W24 and W52 were assessed.

Dupilumab led to a significantly greater percentage decrease in EoEHSS grade/stage total score from baseline vs placebo (least squares mean percentage change −62.3 [95% confidence interval −69.6; −54.9] vs −6.4 [−15.6; 2.8]/−60.2 [−68.3; −52.1] vs −5.2 [−15.5; 5.1]; both P<0.0001) at W24; inflammatory grade/stage subscore also significantly decreased: −74.2 (−84.4; −64.0) vs −3.1 (−16.5; 10.2)/−84.2 (−100.0; −68.2) vs 3.0 (−20.5; 26.6); both P<0.0001. Similar results were reported for architectural subscores. Dupilumab improved overall EoEHSS grade/stage component scores, with only minor improvement reported for DIS, DEC, LPF (Figure). Improvements observed at W24 were maintained and/or further improved in patients who received dupilumab for an additional 28 weeks. In patients who switched to dupilumab at W24, improvements were greater at W52 vs W24, except for DIS and DEC which showed no statistically significant differences between the two timepoints.

Dupilumab 300 mg weekly improved a broad range of histologic aspects of disease in adults and adolescents with EoE at W24, vs placebo, with further improvements at W52. Future studies might investigate how percentage changes in different EoEHSS scores might manifest among dupilumab treatment responders across multi-year longitudinal follow-up.