Journal Article

Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis

Wipperman, Matthew F., Lucendo, Alfredo J., Maloney, Jennifer, Beazley, Bethany, Ruddy, Marcella, Rothenberg, Marc E., Weinreich, David R., McCann, Eilish, Kosloski, Matthew P., Amin, Nikhil, Mannent, Leda P., Sun, Xian, Hirano, Ikuo, Hamilton, Jennifer D., Shabbir, Arsalan, Akinlade, Bolanle, Shumel, Brad, Collins, Margaret H., Yancopoulos, George D., Kamal, Mohamed A., Laws, Elizabeth, Lim, Wei Keat, Giannelou, Angeliki, Bredenoord, Albert J., Patel, Naimish, Aceves, Seema, Patel, Kiran, Spergel, Jonathan M., Dellon, Evan S., Chehade, Mirna

2022

Overview

Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis. We conducted a three-part, phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (Part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo (Part B) up to week 24. Eligible patients who completed Part A or Part B continued the trial in Part C, in which those who completed Part A received dupilumab at a weekly dose of 300 mg up to week 52 (the Part A-C group); Part C that included the eligible patients from Part B is ongoing. The two primary end points at week 24 were histologic remission (≤6 eosinophils per high-power field) and the change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score (range, 0 to 84, with higher values indicating more frequent or more severe dysphagia). In Part A, histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo (difference, 55 percentage points; 95% confidence interval [CI], 40 to 71; P<0.001). In Part B, histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo (difference between weekly dupilumab and placebo, 54 percentage points; 95% CI, 41 to 66 [P<0.001]; difference between dupilumab every 2 weeks and placebo, 56 percentage points; 95% CI, 43 to 69 [not significant per hierarchical testing]). The mean (±SD) DSQ scores at baseline were 33.6±12.41 in Part A and 36.7±11.22 in Part B; the scores improved with weekly dupilumab as compared with placebo, with differences of -12.32 (95% CI, -19.11 to -5.54) in Part A and -9.92 (95% CI, -14.81 to -5.02) in Part B (both P<0.001) but not with dupilumab every 2 weeks (difference in Part B, -0.51; 95% CI, -5.42 to 4.41). Serious adverse events occurred in 9 patients during the Part A or B treatment period (in 7 who received weekly dupilumab, 1 who received dupilumab every 2 weeks, and 1 who received placebo) and in 1 patient in the Part A-C group during the Part C treatment period who received placebo in Part A and weekly dupilumab in Part C. Among patients with eosinophilic esophagitis, subcutaneous dupilumab administered weekly improved histologic outcomes and alleviated symptoms of the disease. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03633617.).

• Publisher: Massachusetts Medical Society
• Subject: Adolescent / Adolescent Medicine / Adult / Allergy / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - adverse effects / Antibodies, Monoclonal, Humanized - therapeutic use / Autoimmune diseases / Biopsy / Child / Cytokines / Deglutition Disorders - drug therapy / Deglutition Disorders - etiology / Deglutition Disorders - pathology / Disease / Double-Blind Method / Dysphagia / Endoscopy / Enteritis / Eosinophilia / Eosinophilic Esophagitis - complications / Eosinophilic Esophagitis - drug therapy / Eosinophilic Esophagitis - pathology / Esophageal diseases / Esophagitis / Esophagus / Gastritis / Gastroenterology / Gastroenterology General / Gastrointestinal diseases / Gene expression / Humans / Immunology / Immunology General / Inflammatory Disease / Injections, Subcutaneous / Interleukin 13 / Interleukin 4 / Leukocytes (eosinophilic) / Monoclonal antibodies / Patient safety / Pediatrics / Pediatrics General / Placebos / Quality of life / Questionnaires / Remission / Teenagers / Treatment Outcome / Young Adult