Dupixent induces histologic remission in up to 68% of children with PPI-refractory EoE
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Key takeaways:
- More than half of patients in the dupilumab groups achieved histologic remission at week 16.
- Higher-exposure dupilumab significantly improved histologic, endoscopic and transcriptomic measures.
Treatment with Dupixent led to histologic remission at week 16 among a greater percentage of pediatric patients with eosinophilic esophagitis refractory to proton-pump inhibitor therapy compared with placebo, according to study results.
Dupixent (dupilumab; Sanofi/Regeneron) was approved by the FDA in January to treat children with EoE aged 1 to 11 years who weigh at least 15 kg.
“Dupilumab, a fully human monoclonal antibody that blocks the interleukin-4 and interleukin-13 pathways, is approved for the treatment of five diseases marked by type 2 inflammation that are often coexistent,” Mirna Chehade, MD, MPH, professor of pediatrics and medicine at Icahn School of Medicine at Mount Sinai and founding director of the Mount Sinai Center for Eosinophilic Disorders, and colleagues wrote in The New England Journal of Medicine. “The efficacy of dupilumab for these indications shows that interleukin-4 and interleukin-13 are the key drivers of the underlying type 2 inflammation.
They continued, “In the LIBERTY EoE TREET trial, a phase 3 trial involving adult and adolescent patients with eosinophilic esophagitis refractory to proton-pump inhibitor therapy, dupilumab therapy improved histologic, symptomatic, endoscopic and molecular outcomes and had an acceptable side-effect profile.”
In the current phase 3, three-part trial, researchers assessed the efficacy of dupilumab in pediatric patients (mean age, 7 years; 76% boys; 82% white) with active EoE refractory to PPI therapy.
In part A, a double-blind, placebo-controlled trial, 102 patients were randomly assigned 2:2:1:1 to subcutaneous higher-exposure dupilumab (n = 37), lower-exposure dupilumab (n = 31) or placebo (n = 34) for 16 weeks. Eligible patients in the dupilumab groups continued on the same regimen (n = 37 and n = 29, respectively) to 52 weeks in part B, while placebo groups were reassigned to higher-exposure (n = 18) or lower-exposure (n = 14) dupilumab. Part C, a 108-week open-label extension study, is ongoing.
Researchers administered dupilumab at each level of exposure in one of four doses tiered according to baseline body weight.
The primary endpoint was histologic remission, defined as peak esophageal intraepithelial eosinophil count of no more than six per high-power field, at week 16. Researchers noted that the mean peak esophageal intraepithelial eosinophil count was 83.3 per high-power field at baseline.
According to study results, 68% of those who received higher-exposure dupilumab achieved histologic remission at week 16, compared with 58% of the lower-exposure dupilumab group and 3% of the placebo group. This corresponded with a 65 percentage point and 55 percentage point difference between higher-exposure and lower-exposure groups, respectively, and placebo.
“The higher-exposure dupilumab regimen led to significant improvements in histologic, endoscopic and transcriptomic measures as compared with placebo,” the researchers wrote.
These improvements were “generally similar” from baseline to week 52, they added, to those from baseline to week 16 among patients who continued the same dupilumab regimen in part B.
According to researchers, serious adverse events were observed in patients receiving dupilumab (part A, n = 3; part B, n = 6).
“This phase 3 trial involving children 1 to 11 years of age with eosinophilic esophagitis showed that dupilumab regimens tiered according to body weight led to histologic remission in a significantly greater percentage of patients than placebo,” Chehade and colleagues wrote. “Improvements in additional histologic, endoscopic and transcriptomic measures were also seen with dupilumab as compared with placebo.”
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