Dupilumab was not only well tolerated but also led to significant, clinically meaningful improvements in histologic, symptomatic, and endoscopic measures of eosinophilic esophagitis (EoE) in adults and adolescents with the inflammatory disease, according to results from a phase 3 study presented at the 2020 American College of Gastroenterology Annual Scientific Meeting.
The investigators evaluated the safety and efficacy of weekly dupilumab 300 mg vs placebo in adults and adolescents with EoE for 24 weeks in part A of a 3-part, randomized, phase 3 study (ClinicalTrials.gov Identifier: NCT03633617). Dupilumab is a fully human monoclonal antibody that blocks the shared receptor component for interleukin (IL)-4 and IL-13, which are involved in type 2 inflammation in EoE.
The trial’s co-primary end points were the proportion of patients that achieved a peak esophageal intraepithelial eosinophil (eos) count of 6 or fewer eos/high-power field (hpf), and the absolute change from baseline in Dysphagia Symptom Questionnaire (DSQ) score at week 24. The absolute change from baseline in eosinophilic esophagitis histologic scoring system (EoEHSS) mean grade and stage scores, absolute change in total EoE Endoscopic Reference Score (EREFS), and the proportion of patients that achieved a peak eos count of fewer than 15 eos/hpf were secondary end points.
Eighty-one patients were randomly assigned to receive dupilumab (n=42) or placebo (n=39). Baseline characteristics were comparable across both arms.
The researchers found that a significantly greater proportion of patients who received dupilumab achieved peak eos counts of 6 or fewer eos/hpf vs patients who received placebo (59.5% vs 5.1%, respectively, P <.001). Patients in the dupilumab arm also more commonly achieved peak eos counts of fewer than 15 eos/hpf compared with patients in the placebo arm (64.3% vs 7.7%, respectively, P <.001).
Further, those treated with dupilumab had a significantly greater change from baseline in DSQ score (least squares [LS] mean difference: −12.32; 95% CI, −19.11 to −5.54; P <.001). This trend continued in analyses of EoEHSS mean grade (LS mean difference: −0.76 [95% CI, −0.91 to −0.61], P <.001), stage scores (LS mean difference: −0.74 [95% CI, −0.88 to −0.60], P <.001), and total EREFS (LS mean difference: −2.9 [95% CI, −3.91 to −1.84], P <.001).
“Dupilumab was generally well tolerated,” the study authors said. Indeed, the most common treatment-emergent adverse events were injection-site reactions (16.7% vs 10.3%) and nasopharyngitis (11.9% vs 10.3%), which occurred at a slightly higher frequency in the dupilumab arm.
Disclosures: This research was sponsored by Sanofi and Regeneron Pharmaceuticals, Inc. Please see the original reference for a full list of disclosures.
Dellon ES, Rothenberg ME, Collins MH, et al. A phase 3, randomized, 3-part study to investigate the efficacy and safety of dupilumab in adult and adolescent patients with eosinophilic esophagitis: results from part A. Presented at: the American College of Gastroenterology Annual Scientific Meeting; October 26-28, 2020. Abstract LB3.