A213 DUPILUMAB EFFICACY IN EOSINOPHILIC ESOPHAGITIS PERSISTS FOR HISTOLOGIC, SYMPTOMATIC, AND ENDOSCOPIC OUTCOMES REGARDLESS OF CONCOMITANT HIGH-DOSE PROTON PUMP INHIBITOR USE

Abstract

Abstract Background Proton-pump inhibitor (PPI) therapy is the most commonly used first-line therapy for eosinophilic esophagitis (EoE) but data informing long-term outcomes are limited. Aims This pre-specified analysis of data from the phase 3 LIBERTY EoE TREET (NCT03633617) study assessed the efficacy of weekly dupilumab vs placebo in patients (pts) with and without concomitant PPI use. Methods Pts with peak intraepithelial eosinophil (eos) count ≥15 eos/high-power field (hpf) after ≥8 weeks’ high-dose PPI were randomized to dupilumab or placebo. Pts on high-dose PPIs at screening remained on a high-dose regimen during the treatment period; switching of PPI types was permitted but new initiation of PPIs was prohibited. Endpoints at Week 24 were: proportion of pts achieving ≤6 eos/hpf, absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) score, % change in peak eos count, absolute change in Endoscopic Reference Score (EREFS) and Histologic Scoring System (HSS) grade/stage scores. Results In Parts A and B, respectively, 61.9% and 71.3% of pts in the dupilumab group and 64.1% and 72.2% in the placebo group were using PPIs at randomization. For pts treated with dupilumab vs placebo in Parts A and B, respectively, ≤6 eos/hpf was achieved by 69.2% (95% confidence interval [CI] 48.2–85.7) vs 8.0% (95% CI 1.0–26.0) and 59.6% (95% CI 45.8–72.4) vs 7.0% (95% CI 2.0–17.0) of pts using PPIs, and by 43.8% (95% CI 19.8–70.1) vs 0% (95% CI 0–23.2) and 56.5% (95% CI 34.5–76.8) vs 4.5% (95% CI 0.1–22.8) of pts not using PPIs. Least squares mean change from baseline in DSQ score for dupilumab vs placebo was –18.5 vs –12.9 and –21.8 vs –14.0 for pts using PPIs in Parts A and B, respectively, and –27.8 vs –3.8 and –28.4 vs –13.3 for those not using PPIs (Figure 1). Dupilumab improved outcomes vs placebo for secondary endpoints, with comparable results in pts with and without concomitant PPI use. Absolute change from baseline in EREFS score is shown in Figure 1. Dupilumab was generally well tolerated. Conclusions Dupilumab improved histologic, symptomatic, and endoscopic aspects of EoE in adults and adolescents, up to 24 weeks, regardless of concomitant high-dose PPI use. Figure 1. Effect of dupilumab 300 mg qw versus placebo on primary endpoints (A) proportion of patients with peak esophageal intraepithelial eosinophil count of ≤6 eos/hpf (B) absolute change from baseline in DSQ total score at Week 24 (C) absolute change from baseline in EREFS total score at Week 24, by concomitant PPI use CI, confidence interval; DSQ, Dysphagia Symptom Questionnaire; EREFS, endoscopic reference score; eos, eosinophils; hpf, high-power field; LS, least squares; PPI, proton pump inhibitor; pt, patient; qw, once weekly; SE, standard error. Funding Agencies Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.