Eosinophilic esophagitis (EoE) is a chronic, allergic inflammatory disease that occurs when there is an increased number of eosinophils in the esophagus. EOE damages the esophagus and impairs its function. Symptoms vary among individuals and age groups. Children with EOE may experience heartburn, vomiting, abdominal discomfort, trouble swallowing, and food refusal. It also can negatively affect their growth and development.
The two main treatments for EoE include diet and medications that were approved to treat other conditions, such as swallowed topical corticosteroids (STCs), proton pump inhibitors (PPI), and monoclonal antibodies. But swallowed topical corticosteroid are associated with side effects, have limited long-term efficacy and safety, must be dosed frequently, and some patients may not respond. Efficacy data of PPI therapy for EoE are heterogenous and variable, and prospective safety data are also lacking, particularly for high dose twice daily PPI therapy for EoE. Monoclonal antibodies such as dupilumab are used in adults and children over age 12.
In January 2024, the FDA approved dupilumab for use in children aged 1 to 11 years who weigh at least 15 kg. Dupilumab blocks the signaling of IL-4 and IL-13, two cytokines involved in inflammation. This medication is administered via injection under the skin. The approval was based on data from the phase 3 EoE KIDS trial. The phase 3 EoE KIDS trial included participants who were unresponsive to at least 8 weeks of treatment with proton pump inhibitors, had a peak intraepithelial eosinophilic count of at least 15/high power field in two of the three esophageal regions and symptoms of EoE in the months prior to screening.
The trial was divided into part A, a 16-week, in which patients were randomly assigned to high-dose dupilumab (n = 37), low-dose dupilumab (n = 31) or placebo (n = 34). Patients who completed part A could advance to part B, a 36-week, in which patients on dupilumab continued their regimens, while those on placebo switched to high or low doses of dupilumab.
According to results, 68% of children who received higher doses of dupilumab and 3% of those who received placebo achieved histological disease remission (≤ 6 eosinophils/high power field). This was maintained through week 52, with 17 (53%) of the 32 children who were treated with dupilumab in parts A and B and eight (53%) of the 15 children who switched to high dose dupilumab from placebo in part B.
Further, researchers found that high-dose dupilumab reduced caregiver-reported EoE signs at week 16, which were maintained through part B of the study. In addition, higher exposure dupilumab improved weight gain at weeks 16 and 52.
Moreover, dupilumab also was well-tolerated. The safety profile through 16 weeks was like the safety profiles for adolescents and adults using dupilumab through 24 weeks. The most common adverse events included injection site reactions, upper respiratory tract infections, arthralgia, and herpes viral infections.
