Dupilumab sustains histologic, endoscopic improvement up to 1 year in children with EoE
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Key takeaways:
- At 16 weeks, 68% of patients on high-dose dupilumab achieved reduced peak eosinophil counts vs. 3% on placebo.
- High-dose dupilumab also decreased the severity and extent of histologic measures.
VANCOUVER, British Columbia — High-dose dupilumab achieved significant improvements in histologic and endoscopic measures through 52 weeks in children aged 1 to 11 years with eosinophilic esophagitis, according to late-breaking data.
“Eosinophilic esophagitis, or EoE, is a chronic, progressive type 2 inflammatory disease with substantial impact on quality of life and increasing incidence and prevalence,” Mirna Chehade, MD MPH, founding director of the Mount Sinai Center for Eosinophilic Disorders and professor of pediatrics and medicine at the Icahn School of Medicine, said during her presentation at the ACG Annual Scientific Meeting. “EoE has similar underlying histology in children and adults. However, children have more heterogeneous and nonspecific symptoms with less dysphasia and less remodeling than adults.”
She continued, “There are no approved treatments for EoE in children aged less than 12 years. Dupilumab, a fully human monoclonal antibody, blocks key drivers of type 2 allergic inflammation and is approved for adults and adolescents aged 12 years and older, weighing at least 40 kilograms.”
In the phase 3 KIDS trial, Chehade and colleagues assessed the efficacy and safety of dupilumab compared with placebo in children aged 1 to 11 years with active EoE. Eligible participants were unresponsive to at least 8 weeks of treatment with proton pump inhibitors, had a peak intraepithelial eosinophilic count of at least 15/hpf in two of the three esophageal regions and symptoms of EoE in the months prior to screening.
The trial was divided into part A, a 16-week, double-blind treatment period, in which patients were randomly assigned to weight-tiered high-dose dupilumab (n = 37), low-dose dupilumab (n = 31) or placebo (n = 34). Patients who completed part A could advance to part B, a 36-week, extended active treatment period in which patients on dupilumab continued their regimens, while those on placebo switched to high or low doses of dupilumab.
The study’s primary endpoint was proportion of patients who achieved peak esophageal intraepithelial eosinophil counts of 6 eos/hpf or fewer at weeks 16 and 52.
Chehade noted that the reported analysis only included patients assigned to high-dose dupilumab or placebo; baseline characteristics of the two groups were similar.
According to results, 68% of patients in the high-dose dupilumab group achieved the primary endpoint at week 16 compared with 3% on placebo. This was maintained through week 52 in patients who continued on high-dose dupilumab (63%) and increased in those who switched from placebo to high-dose dupilumab (53%).
Researchers also found that high-dose dupilumab decreased the severity and extent of histologic measures of EoE at weeks 16 and 52 compared with placebo, including a significant change from baseline in EoE-HSS grade score (–0.88 vs. 0.02 and –0.97 vs. –0.89, respectively). Similar results were reported for EoE-HSS stage score at both time points (–0.84 vs. –0.05 and –0.89 vs. –0.86).
In addition, high-dose dupilumab improved endoscopic aspects of EoE compared with placebo, with absolute changes in EoE-EREFS of –3.5 vs. 0.3, respectively, from baseline to week 16 and –4.8 vs. –3.6 at week 52.
Clinically, researchers also found that high-dose dupilumab reduced caregiver-reported EoE signs at week 16, which were maintained through the second part of the study.
“The change from baseline in the proportion of days with one or more EoE signs was numerically higher in the dupilumab treatment group compared to placebo, and this change was maintained up to week 52.” Chehade told attendees.
“Since many of the children with EoE have failure to thrive, we were really interested to look at body weight for age percentile in these patients,” she added. “What we saw was higher-exposure dupilumab improved weight gain at weeks 16 and 52.”
Dupilumab also was well-tolerated, with a safety profile similar to what has been described for adults and adolescents with EoE.
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Chehade M, et al. Dupilumab improves histologic, endoscopic and transcriptomic aspects of eosinophilic esophagitis (EoE) in children aged 1 to <12 years: 52-week results from the phase 3 EoE KIDS trial. Presented at: ACG Annual Scientific Meeting; Oct. 20-25, 2023; Vancouver, British Columbia (hybrid meeting).
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