Sustained Improvement in Eosinophil Counts and HSS Scores in Patients With Eosinophilic Esophagitis Treated With Dupilumab: 52-Week Results From the LIBERTY EoE TREET Study

Introduction: Eosinophilic esophagitis (EoE) is a chronic, progressive, type 2 inflammatory disease associated with significant esophageal pathology. Dupilumab is approved for EoE treatment based on the 3-part, double-blind, placebo-controlled, phase 3 LIBERTY-EoE-TREET study (NCT03633617). Weekly (qw) dupilumab 300 mg demonstrated improvements vs placebo in histologic, symptomatic, and endoscopic features of EoE in Parts A and B. The EoE histology scoring system (HSS) is a validated measure, comprised of 8 histologic components, that scores severity of changes (grade) and extent of pathology (stage). Here we assess histologic aspects of EoE in the Part C extension, in which all patients received dupilumab. Methods: Patients in Part B were randomized to dupilumab 300 mg qw, dupilumab 300 mg q2w, or placebo qw for 24 weeks (W). The current analysis includes patients who entered the extension after completing Part B and receiving dupilumab 300 mg qw. Results: In the extension, 74 Patients continued dupilumab qw and 37 switched from placebo to dupilumab qw. At extension onset (W24) higher proportions of Patients treated with dupilumab than placebo had achieved eosinophil counts ≤1, ≤6, and < 15 per high-powered field (Table 1). During the extension effects were sustained with continued dupilumab, and responder rates increased at W52 in Patients switched to dupilumab (Table 1). At extension onset change in basal zone hyperplasia (BZH) HSS mean (SD) grade score from baseline of the placebo-controlled part of the study had improved with dupilumab vs placebo (–2.052 [0.732] vs –0.471 [1.132]). Continued dupilumab sustained BZH improvements to W52 (–2.132 [0.744]), and placebo Patients who switched at W24 improved at W52 (–2.176 [0.583]). Most HSS component grade scores showed a similar pattern (Table 1), except dilated intercellular spaces and dyskeratotic epithelial cells (less sustained effects), and lamina propria fibrosis (insufficient data). HSS component mean stage scores were similar. There were no consistent correlations between change in HSS component grade/stage scores and change in DSQ score across treatment groups at 52 weeks, but some moderate intragroup correlations were found. Dupilumab qw was well tolerated. Conclusion: Dupilumab treatment for 52W led to sustained improvements in eosinophil counts and the severity/extent of pathologic changes as measured by HSS grade/stage component scores. Similar improvements occurred after switching from placebo to dupilumab at W24. Table 1. - Part B–C eosinophil count responders and change in HSS component mean grade scores from Part B baseline. Includes patients who entered Part C who were originally randomized to either dupilumab 300 mg qw or placebo qw in Part B and received dupilumab 300 mg qw in Part C 24 weeks (baseline of Part C) 52 weeks Proportion of patients achieving eosinophil count, n/N (%) Peak esophageal intraepithelial eosinophil count of ≤1eos/hpf Dupilumab/dupilumab qw 23/74 (31.1) 20/65 (30.8) Placebo/dupilumab qw 0/37 (0) 6/37 (16.2) Peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf Dupilumab/dupilumab qw 48/74 (64.9) 55/65 (84.6) Placebo/dupilumab qw 2/37 (5.4) 25/37 (67.6) Peak esophageal intraepithelial eosinophil count of < 15 eos/hpf Dupilumab/dupilumab qw 66/74 (89.2) 65/65 (100.0) Placebo/dupilumab qw 3/37 (8.1) 29/37 (78.4) Change in HSS component grade score, mean (SD) Basal zone hyperplasia Dupilumab/dupilumab qw n=71–2.052 (0.732) n=63–2.132 (0.744) Placebo/dupilumab qw n=34–0.471 (1.132) n=36–2.176 (0.583) Eosinophilic inflammation Dupilumab/dupilumab qw n=72–1.662 (0.577) n=63–1.873 (0.520) Placebo/dupilumab qw n=34–0.255 (0.739) n=36–1.657 (0.481) Eosinophilic abscesses Dupilumab/dupilumab qw n=72–0.551 (0.528) n=63–0.587 (0.558) Placebo/dupilumab qw n=34–0.137 (0.435) n=36–0.482 (0.386) Eosinophilic surface layering Dupilumab/dupilumab qw n=72–1.287 (0.867) n=63–1.386 (0.894) Placebo/dupilumab qw n=34–0.284 (0.947) n=36–1.306 (0.766) Dilated intercellular spaces Dupilumab/dupilumab qw n=71–0.235 (0.486) n=63–0.169 (0.493) Placebo/dupilumab qw n=34–0.049 (0.598) n=36–0.139 (0.467) Surface epithelial alteration Dupilumab/dupilumab qw n=72–0.704 (0.748) n=63–0.741 (0.811) Placebo/dupilumab qw n=34–0.255 (0.932) n=36–0.889 (0.862) Dyskeratotic epithelial cells Dupilumab/dupilumab qw n=72–0.065 (0.183) n=63–0.011 (0.216) Placebo/dupilumab qw n=340.049 (0.349) n=360.019 (0.210) Lamina propria fibrosis Dupilumab/dupilumab qw n=0 n=1–0.667 (N/A) Placebo/dupilumab qw n=0 n=0 eos/hpf, eosinophils per high-powered field; HSS, histology scoring system; N/A, not applicable; qw, weekly; SD, standard deviation.