Dupilumab sustains histological remission in children with EoE

Treatment with higher-dose dupilumab results in sustained improvements in histologic and endoscopic measures of eosinophilic esophagitis (EoE) in children, regardless of prior use of swallowed topical corticosteroids (STCs), according to a subanalysis presented at ESPGHAN 2024.

“EoE is a chronic, progressive, type 2 inflammatory disease of the oesophagus, and there are different molecules we can consider as first-line treatment. STCs are commonly used to treat EoE; however, they are associated with side effects, and some patients may not respond to the treatment,” said Dr Salvatore Oliva from the Pediatric Gastroenterology and Liver Unit, Maternal and Child Health Department, Sapienza University of Rome, Rome, Italy.

Hence, the researchers conducted a subanalysis of the phase III EoE KIDS trial involving children aged 1 to <12 years with EoE. These participants were stratified by prior STC use and prior inadequate response, intolerance, or contraindication to STC at baseline.

In part A of the study, participants were randomized to receive weight-tiered, higher-dose* dupilumab or placebo for a 16-week double-blind treatment period.

Upon completion of the double-blind treatment period, 55 participants entered the extended active treatment period (part B), in which all children were treated with higher-dose dupilumab for an additional 36 weeks. Patients receiving dupilumab were continued on the same regimen (n=37), whereas patients receiving placebo initially were switched to dupilumab (n=18) for up to 52 weeks.

At week 16 (part A), more patients treated with higher-dose dupilumab achieved the primary endpoint of histological remission (peak eosinophil count [PEC] of ≤6 eos/hpf**) than those treated with placebo, irrespective of STC use (with STC: 60.7 percent vs 0 percent; p<0.0001; without STC: 88.9 percent vs 14.3 percent; p<0.05).

In part B, patients who continued treatment with higher-dose dupilumab demonstrated a sustained histological remission at week 52 (50 percent [with STC use] and 100 percent [without STC use]). [ESPGHAN 2024, abstract G-O029]

Among those who switched from placebo to higher-dose dupilumab, 50 percent (with STC use) and 100 percent (without STC use) achieved their first histological remission at week 52.

Dupilumab recipients also demonstrated a greater decrease in EREFS*** total score than the placebo recipients at week 16 (least squares [LS] mean, -3.8 vs 0.3 [with STC use] and -2.1 vs -0.7 [without STC use], which were sustained through week 52.

In terms of symptom assessment, both higher-dose dupilumab and placebo-higher-dose dupilumab groups showed no significant differences in the caregiver-reported symptoms (number of days with ≥1 EoE sign), as shown by the Pediatric EoE Sign/Symptom Questionnaire-caregiver version scores at week 12 (with STC: -0.27 vs -0.13; without STC: -0.26 vs -0.27) and week 52 (with STC: -0.28 vs -0.50; without STC: -0.37 vs -0.22).

“Overall, up to week 52, improvements to histologic, endoscopic, and symptomatic aspects of EoE continued or were maintained in patients continuing dupilumab higher exposure and even in those patients who switched from placebo to dupilumab higher exposure regardless of prior STC use or prior inadequate response, intolerance, or contraindication to STCs,” Oliva concluded.

“Dupilumab, a fully human monoclonal antibody against interleukin (IL)-4 and IL-13, key drivers of type 2 inflammation, has been approved for EoE in the US for patients aged ≥1 year, weighing ≥15 kg, and in Europe for adult and adolescent patients aged ≥12 years, weighing ≥40 kg” he noted.