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 . 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 
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.
- 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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Table of Contents: UEGW 2022
Letter from the Editor
UEGW 2022 Highlights Podcast
IBD in 2022
Fast recapture of response with ozanimod after withdrawal in UC
Ozanimod treatment prompted substantial response after failure of response to induction
Etrasimod shows advantage over placebo in UC
Etrasimod reduces adaptive immune cells in the periphery in UC
Favourable maintenance rates for risankizumab also in delayed responders with CD
IL-23 inhibition reduces inflammatory biomarkers in pre-treated UC
Maintained symptom control with mirikizumab in UC
Mirikizumab successfully resolves active histologic inflammation in UC
Upadacitinib for CD: remarkable efficacy in induction therapy
Sustained maintenance results with upadacitinib in UC
Start low with brepocitinib and ritlecitinib in UC
Another chance for TYK2 inhibition in UC
Small molecule obefazimod shows promise in UC
Pivotal results of etrolizumab for CD partly disappointing
Better results for vedolizumab in early CD
Some patients with limited CD may benefit from an early surgical intervention
Dose-interval of adalimumab might be prolonged in CD patients in stable remission
What Is Hot in Upper GI Disorders?
Less ulcer bleeds early after H. pylori eradication in aspirin users
Dupilumab effective in paediatric patients with eosinophilic oesophagitis
Neoplasia in Barrett’s oesophagus: the earlier the intervention, the better the long-term outcome
Hepatology in 2022
Favourable pancreatitis outcomes with procalcitonin-based algorithm to guide antibiotic use
Portal hypertension is associated with poor prognosis in cirrhotic patients
Chances of transplant-free survival in PSC enhanced by colectomy with ileostomy
SARS-CoV-2: Booster doses of key importance for cirrhotic patients
What Is New in Pancreatic Cancer and Pancreatitis?
Fewer long-term interventions after delayed drainage in necrotising pancreatitis
Detection of Europe´s deadliest cancer: much room for improvement
Colorectal Carcinoma: Improving Diagnosis and Therapy
Immunotherapy response may be modulated by microbiome
Computer-aided colonoscopies improved adenoma detection rates
Screening-detected colorectal cancers may have superior surgical outcomes