Dupilumab is a VelocImmune derived human monoclonal antibody against the interleukin (IL4) receptor and inhibits IL-4 and IL-13 signaling. It is effective in the treatment of allergic, atopic, and type 2 diseases, and to assess its efficacy and safety in patients with eosinophilic esophagitis (EoE), a phase 2 study of adults with EoE (2 episodes of dysphagia per week with peak esophageal eosinophilic density of 15 or more eosinophils per high-power field) from 5/12/2015 through 11/9/2016 at 14 sites. Participants were randomly assigned to groups that received weekly subcutaneous injections of dupilumab (300 mg, N = 23), or placebo (N = 24) for 12 weeks. The primary endpoint was changed from baseline to week 10 in Straumann dysphagia instrument (SDI). Patientreported outcome (PRO) histologic features of EoE were assessed (peak esophageal intraepithelial eosinophilic count and EoE histologic scores, endoscopically visualized features (endoscopic reference score), esophageal distensibility, and safety.
The mean SDI and PRO score were 6.4 when the study began. In the dupilumab group, SDI/PRO scores were reduced by a mean value of 3 at week 10, compared with a mean reduction of 1.3 in the placebo group. At week 12, dupilumab reduced the peak esophageal intraepithelial eosinophil count by a mean 86.8 eosinophils per high-power field (reduction of 107.1% vs placebo), the EoE histologic scoring system (HSS) severity score by 68.3% and the endoscopic reference score by 1.6%. Dupilumab increased esophageal distensibility by 18% vs placebo. Higher proportions of patients in the dupilumab group developed injection site erythema (35% vs 8% in placebo group) and nasopharyngitis (17% vs 4% in the placebo group).
In a phase 2 trial of patients with active EoE, dupilumab reduced dysphagia, histologic features of disease, including eosinophilic infiltration and a marker of type 2 inflammation and abnormal endoscopic features compared with placebo. It was generally well tolerated.
Hirano, I., Dellon, E., Hamilton, J., et al. “Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults with Active Eosinophilic Esophagitis.” Gastroenterology 2020; Vol. 158, pp. 111-122.