Dupilumab effective in paediatric patients with eosinophilic oesophagitis

In the first phase 3 trial in paediatric patients with eosinophilic oesophagitis, therapy with the IL-4/IL-13 receptor blocker dupilumab led to a significant reduction of peak oesophageal intraepithelial eosinophil count compared with placebo at week 16. In addition, dupilumab showed a favourable safety profile with more patients in the placebo group discontinuing therapy due to adverse events.

Dupilumab, a fully-human, monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 inflammation, and might therefore be active in eosinophilic oesophagitis, a chronic, progressive, type 2 inflammatory disease. Indeed, in the phase 3 LIBERTY-EoE-TREET trial (NCT03633617), dupilumab already demonstrated clinically meaningful improvements in histological, symptomatic, and endoscopic outcomes in adolescents and adults with eosinophilic oesophagitis. As a result, the FDA recently approved dupilumab as the first and only agent for treatment of adults and children ≥12 years with eosinophilic oesophagitis.

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 eosinophilic oesophagitis [1]. All included participants had failed to respond to proton-pump inhibitors. The study consists of 3 parts. In the double-blind part A, 102 participants we randomised 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. Prof. Evan S. Dellon (University of North Carolina School of Medicine in Chapel Hill, NC, USA) focussed on the primary outcomes of part A at week 16, especially from the high-dose group, noting that parts B and C are still ongoing. 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 symptom 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% on placebo (P<0.0001 for each comparison; see Figure). Dupilumab was also superior to placebo in a couple of secondary endpoints, such as the reduction of peak oesophageal intraepithelial eosinophil count at week 16 from baseline. This parameter was reduced by 86% in the higher dupilumab dose group and increased with 21% in the placebo group (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 with 0.29 kg in the placebo group. Although this difference failed to reach statistical significance, Prof. Dellon described it as a “substantial increase in body weight, almost a normalisation”.

Figure: Dupilumab improved the proportion of participants achieving peak oesophageal eosinophil count ≤6 eos/hpf at week 16 [1]



Eos, eosinophils; hpf, high power field; SC, sub-cutaneous. ^aBiopsies were collected from 3 oesophageal regions (proximal, mid, distal) at screening and week 16 for histology.

The rate of adverse events and treatment discontinuation due to adverse events prior to week 16 were higher in the placebo groups compared with the dupilumab group.

1. 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, 8–11 October, Vienna, Austria.

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Posted on 2 December 202229 February 2024