Dupilumab shows benefit in young children with EoE

Treatment with dupilumab significantly improves histologic and endoscopic measures of eosinophilic esophagitis (EoE) in young children aged 1–11 years, according to the phase III EoE KIDS trial presented at ESPGHAN 2023.

Dupilumab is FDA-approved for the treatment of adults and adolescents aged ≥12 years and weighing ≥40 kg with EoE. [www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-eosinophilic-esophagitis-chronic-immune-disorder]

“However, there are no approved treatments for EoE in children aged <12 years,” said Dr Mirna Chehade from Icahn School of Medicine at Mount Sinai in New York, US.

Hence, the researchers conducted the EoE KIDS part A study to analyse 102 children aged 1–11 years with active EoE (mean duration of 2.85 years) who were unresponsive to ≥8 weeks of proton pump inhibitor treatment. Participants were randomized in a 1:1:1 ratio to receive high-dose (n=37) or low-dose (n=31) dupilumab subcutaneously based on their body weight (≥5 to ≥60 kg) or placebo (n=34) for 16 weeks.

At week 16, significantly more children treated with either high- or low-dose dupilumab achieved a peak oesophageal eosinophil count of ≤6 eos/hpf* compared with placebo (68.0 percent and 58.0 percent, respectively, vs 3.0 percent; p<0.0001). [ESPGHAN 2023, abstract G-EP012]

Patients in the high-dose dupilumab arm also had an 86-percent reduction in peak oesophageal eosinophil count from baseline to week 16, while those on placebo had a 21-percent increase (p<0.0001).

Significant reductions in histologic scores were also observed in the high-dose dupilumab arm over the placebo arm (least squares [LS] mean change from baseline, -0.88 vs 0.02 [HSS** grade] and -0.84 vs 0.05 [HSS stage score]; p<0.0001 for both).

Endoscopic features of EoE were significantly improved, as shown by a decrease in EREFS*** total score, with high-dose dupilumab over placebo at week 16 (LS mean change from baseline, -3.5 vs 0.3; p<0.0001).

“Histologic, anatomic, and cellular secondary endpoints were also analysed for the low-dose dupilumab regimen, with all being nominally significant and generally comparable with the high-dose regimen,” Chehade noted.

In an exploratory analysis, the high-dose dupilumab regimen numerically improved body weight for age percentile by 3.09 compared to 0.29 in the placebo arm.

All other symptomatic outcomes, such as Pediatric EoE Sign/Symptom Questionnaire-caregiver version and the number of days with ≥1 sign related to EoE, were improved with high-dose dupilumab compared with placebo at week 16.

In terms of safety, the overall rate of adverse events (AEs) was lower in the dupilumab arm vs the placebo arm (79.0 percent vs 91.0 percent), with no treatment discontinuation observed with the dupilumab regimen.

COVID-19 (21 percent), rash (9 percent), and headache (8 percent) were the most commonly reported AEs in the dupilumab arm, but all were considered mild or moderate in severity.

Safety results through week 16 were consistent with the known safety profile of dupilumab, noted Chehade.

“Overall, this phase III trial assessing dupilumab vs placebo in children aged 1–11 years with active EoE met its primary endpoint of histologic disease remission at week 16,” said Chehade.

“This trial is the fifth paediatric pivotal trial across three type 2 inflammatory diseases, reinforcing the well-established efficacy and safety profile of dupilumab,” she added.