S0404 Improved Histopathologic Features in Patients With Eosinophilic Esophagitis: Results and Analyses From a Phase 3, Randomized, Placebo-Controlled Trial of Budesonide Oral Suspension

Abstract

INTRODUCTION: The Eosinophilic Esophagitis Histology Scoring System (EoEHSS) is a validated measure that assesses the grade (severity) and stage (extent) of eight histopathologic features in eosinophilic esophagitis (EoE). We evaluated the effect of budesonide oral suspension (BOS) on EoEHSS scores in patients with EoE. METHODS: This was a phase 3, 12-week, randomized, double-blind, placebo-controlled trial of BOS (2.0 mg b.i.d.) in patients 11–55 years old with EoE and dysphagia (NCT02605837). Secondary efficacy endpoints were change in peak eosinophil counts and EoEHSS scores from baseline to week 12. Post hoc analyses examined the change in (1) EoEHSS scores by esophageal region and histologic response threshold (≤1, ≤6 and <15 eosinophils/high-power field [eos/hpf]) and (2) individual features of the EoEHSS, after 12 weeks of therapy. RESULTS: Overall, 318 patients received ≥1 dose of BOS (n = 213) or placebo (n = 105). The mean age (standard deviation) was 33.9 (12.0) years. The trial met its co-primary and key secondary efficacy endpoints (data not shown). BOS-treated patients had greater least-squares mean (standard error of the mean) changes in peak eosinophil counts (−55.2 [3.4] vs −7.6 [4.3] eos/hpf; P < 0.001) and EoEHSS scores than placebo-treated patients (grade, −0.22 [0.01] vs −0.03 [0.02]; stage, −0.20 [0.01] vs −0.00 [0.02]; both, P < 0.001; Table 1); changes in EoEHSS scores were similar by esophageal region (Table 1). Mean changes in EoEHSS scores were similar across histologic response thresholds (Table 1). Significantly greater improvements were observed with BOS than with placebo for all features except dyskeratotic epithelial cells (Figures 1 and 2); greatest improvements with BOS therapy were for eosinophilic inflammation (EI) (grade, −1.36 [0.07] vs −0.22 [0.09]; stage, −1.40 [0.08] vs −0.10 [0.10]; both, P < 0.001) and basal zone hyperplasia (BZH) (grade, −1.56 [0.08] vs −0.28 [0.11]; stage, −1.60 [0.09] vs −0.30 [0.12]; both, P < 0.001). BOS was generally well tolerated. CONCLUSION: Improvements in EoEHSS grade and stage scores were observed for BOS- versus placebo-treated patients in most histopathologic features after 12 weeks of therapy; the greatest improvements were for EI and BZH. This demonstrates that treatment with BOS leads to greater reductions in both severity and extent of histopathologic alterations than with placebo, and shows the importance of the EoEHSS in monitoring EoE disease activity in an independent and more comprehensive way compared with peak eosinophil counts.Table 1.: Change in EoEHSS grade and stage scores from baseline to week 12 of therapy, stratified by treatment arm, esophageal region and histologic response threshold*Figure 1.: Change in LS mean (SEM) grade* (severity) scores for the individual features of the EoEHSS from baseline to week 12 of therapy, stratified by treatment arm.Figure 2.: Change in LS mean (SEM) stage* (extent) scores for the individual features of the EoEHSS from baseline to week 12 of therapy, stratified by treatment arm.