- Chehade M, et al. Dupilumab improves histological and endoscopic features of eosinophilic oesophagitis in children aged 1-11 years in the phase 3 EoE KIDS trial. LB14, UEG Week 2022, Vienna, Austria, 8–11 October.
In the phase 3 LIBERTY-EoE-TREET (NCT03633617), dupilumab demonstrated already clinically meaningful improvements in histological, symptomatic, and endoscopic outcomes in adolescents and adults with eosinophilic oesophagitis (EoE). As a results of this trial, the Food and Drug administration (FDA) recently approved dupilumab as the first and only agent for treatment of adults and children 12 years and older with EoE.
The phase 3 EoE KIDS trial (NCT04394351) aimed to evaluate the efficacy, safety, and tolerability of dupilumab versus placebo in paediatric patients, aged 1–11 years, with active EoE1. All included participants had failed to respond to proton-pump inhibitors (PPIs). The study consists of 3 parts. In the double-blind part A, 102 participants we randomized 1:1:1 to 2 doses of dupilumab or placebo and treated for 16 weeks. In part B, all participants will be offered dupilumab, and part C will be an open-label extension period up to 108 weeks.
“For this presentation, I will focus on the primary outcomes at week 16, especially from the high dose group, and please keep in mind that part B and C are ongoing,” explained Prof. Evan S. Dellon (University of North Carolina School of Medicine in Chapel Hill, NC, USA). All participants had to have baseline oesophageal biopsies with a peak intraepithelial eosinophil count ≥15 eosinophils(eos)/high power field (hpf) in ≥2 of the 3 oesophageal regions, but there was no symptoms threshold to be included.
At week 16, 68% of participants treated with the higher dupilumab dose and 58% with the lower dose achieved the primary endpoint, a peak oesophageal intraepithelial eosinophil count ≤6 eos/hpf compared with 3% with placebo (P<0.0001 for each comparison). Dupilumab was also superior to placebo in a couple of secondary endpoints, such as the reduction of peak oesophageal intraepithelial eosinophil counts at week 16 from baseline. This parameter was reduced by 86% in the higher dupilumab dose group and increased in placebo by 21% (P<0.0001). The high dose dupilumab regimen reduced histologic scores at week 16.
Regarding clinical symptoms, a numeric improvement was seen in the dupilumab group. Participants in the dupilumab group gained 3.09 Kg weight compared to 0.29 Kg in the placebo group. Although this difference failed to reach statistical significance, this is what Prof. Dellon described as a “substantial increase in body weight, almost a normalisation”.
The rate of adverse events and treatment discontinuation due to adverse events prior to week 16 was higher in the placebo groups compared with the dupilumab group.