Dupilumab achieved histologic remission in 68% of pediatric patients with eosinophilic esophagitis compared with just 3% for placebo, according to a recent study. 

The researchers, led by Mirna Chehade, of the Mount Sinai Center for Eosinophilic Disorders at the Icahn School of Medicine, investigated the efficacy of dupilumab in pediatric patients aged 1 to 11 years with eosinophilic esophagitis (EoE) in a phase III trial. The randomized, double-blind, placebo-controlled trial evaluated histologic remission and secondary outcomes in patients who were unresponsive to proton-pump inhibitors.

Published in The New England Journal of Medicine, the trial enrolled 102 patients (76% male, 82% White) with active eosinophilic esophagitis who were randomly assigned in a 2:2:1:1 ratio to receive either a higher- or lower-exposure dupilumab regimen or placebo for 16 weeks (part A). At the end of Part A, eligible patients continued on their assigned dupilumab regimen, whereas those in the placebo group were reassigned to either dupilumab regimen for an additional 36 weeks (part B). Dupilumab dosing was weight-based, and subcutaneous injections were administered every 2 weeks. The primary endpoint of the trial was histologic remission, defined as a peak esophageal intraepithelial eosinophil count of six or fewer per high-power field at week 16.

After a follow-up of 16 weeks, histologic remission was achieved in 68% (n = 25/37) of the patients in the higher-exposure group, 58% (n = 18/31) in the lower-exposure group, and 3% (n = 1/34) in the placebo group. The difference between the higher-exposure group and placebo was 65 percentage points (95% confidence interval [CI] = 48–81, P < .001). There was a 55 percentage-point difference between the lower-exposure group and placebo (95% CI = 37–73, P < .001). Significant improvements were observed in histologic, endoscopic, and transcriptomic measures, including reductions in type 2 inflammation gene-expression signatures in the higher-exposure group, as shown by lower normalized enrichment scores for the type 2 inflammation and eosinophilic esophagitis diagnostic panel gene sets. After 52 weeks, the patients who continued dupilumab demonstrated sustained histologic and endoscopic improvements, while those switching from placebo showed comparable benefits.

Adverse events were more frequent in the dupilumab groups compared with the placebo group. Common adverse events included injection-site pain, headache, nausea, and COVID-19 infections. Serious adverse events were reported in three patients during part A and in 6 patients overall during part B. No deaths resultant from adverse events were reported.

The researchers noted study limitations, including the challenge of assessing symptoms in young pediatric patients as a result of cognitive and feeding adaptations, as well as the absence of a placebo group in part B, which limited direct comparisons beyond week 16. 

Dupilumab significantly increased histologic remission in pediatric patients with EoE and reduced markers of type 2 inflammation.

Full disclosures can be found in the published study.