Dupilumab as an Adjunct to Oral Immunotherapy in Pediatric Patients With Peanut Allergy
R. Sharon Chinthrajah, Sayantani Sindher, Kari C. Nadeau, Jeffrey Leflein, Jonathan M. Spergel, Daniel Petroni, Stacie M. Jones, Thomas B. Casale, Julie Wang, Warner W. Carr, Wayne G. Shreffler, Robert A. Wood, Erik Wambre, Jinzhong Liu, Bolanle Akinlade, Amanda Atanasio, Jamie Orengo, Jennifer D. Hamilton, Mohamed Kamal, Andrea T. Hooper, Kiran Patel, Elizabeth Laws, Leda Mannent, Daniel C. Adelman, Anoshie Ratnayake, Allen Radin
Abstract
BACKGROUND: Peanut allergy is a common, life-threatening food allergy in children. We evaluated whether dupilumab, which blocks the activity of interleukin (IL)-4/IL-13, enhances the efficacy of oral immunotherapy (OIT) AR101 in pediatric patients with peanut allergy. METHODS: A Phase II, multicenter, randomized, double-blind study was conducted in the USA (NCT03682770) in pediatric patients (6-≤ 17 years old) with confirmed peanut allergy. Patients were randomized 2:1 to receive dupilumab + OIT or placebo + OIT during a 28-40-week up-dosing period. Patients in the dupilumab + OIT group were re-randomized 1:1 and received dupilumab + OIT or placebo + OIT during 24-week OIT maintenance, undergoing a 2044 mg (cumulative) of peanut protein double-blind, placebo-controlled food challenge (DBPCFC) following up-dosing, maintenance, and at 12-week post-treatment follow-up. RESULTS: The study enrolled 148 patients, 123 of whom were included in the modified full analysis set, with a mean age of 11.1 years. Dupilumab + OIT treatment (n = 84) led to a 20.2% increase (p < 0.05) in the number of patients who passed a DBPCFC to 2044 mg (cumulative) of peanut protein following the up-dosing period versus placebo (OIT alone, n = 39). Following the OIT maintenance period, continuous dupilumab treatment improved the number of patients who passed a DBPCFC to 2044 mg (cumulative) of peanut protein versus patients continuously on OIT alone (16.6% difference [95% CI -9.7, 42.8], p = 0.2123). Safety was consistent with known dupilumab safety profile. CONCLUSIONS: Dupilumab provided a modest increase efficacy of OIT in children and adolescents with peanut allergy, though it did not provide protection against OIT-related anaphylaxis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03793608.