VANCOUVER, British Columbia — Treatment with higher-exposure dupilumab (Dupixent) led to sustained improvements in the reduction of peak esophageal intraepithelial eosinophil counts among children ages 1 to 11 with eosinophilic esophagitis (EoE), long-term results from the phase III EoE KIDS trial showed.
The proportion of patients achieving peak counts — ≤20 eosinophils/mm2 — at week 16 was 68% with higher-exposure dupilumab compared with 3% for those who received placebo, reported Mirna Chehade, MD, of the Mount Sinai Center for Eosinophilic Disorders and Icahn School of Medicine at Mount Sinai in New York City.
At 52 weeks, when the placebo patients were switched over to higher-exposure dupilumab, 53% achieved peak eosinophil counts compared with 63% of those who were initially on dupilumab, Chehade noted during a late-breaking presentation at the American College of Gastroenterology annual meeting.
Secondary endpoints including histologic and endoscopic measures were also significant at 16 weeks and improved in those who switched from placebo to the drug by 52 weeks.
Of note, higher-exposure dupilumab also led to better rates of weight gain. At week 16, the 32 children in the placebo group had a gain of 0.29% in body weight compared with an increase of 3.09% among the 37 children taking higher-exposure dupilumab. However, at 52 weeks, when all the children were on higher-exposure dupilumab, the 16 children originally on placebo achieved a 5.48% increase in body weight compared with a 5.96% increase among the 35 children who had been on dupilumab.
Essentially, the placebo kids caught up with the others, Chehade said.
EoE is a chronic, progressive, type 2 inflammatory disease with increasing incidence and prevalence that has substantial effects on quality of life. The underlying histology is similar in children and adults, but children have more heterogeneous and non-specific symptoms, with less dysphagia and less remodeling.
There are no approved treatments for EoE in children under the age of 12. Dupilumab, a fully human monoclonal antibody, blocks key drivers of type 2 inflammation and is approved for EoE in patients 12 and up.
Session moderator Samir Shah, MD, of the Alpert Medical School at Brown University in Providence, Rhode Island, noted that “this is a very important study. We don’t have great treatments for EoE in pediatrics or in adults.”
“The weight gain seen in these patients is really important,” he said. “The fact that the placebo patients caught up very quickly to the treatment group shows that the medicine works very quickly. These are compelling data, even more so because we did not see any safety signals, which, of course, is important in treating children. That is consistent with the data we have been seeing in adults and adolescents.”
To be eligible for inclusion in the trial, children had to be 1 to 11 years old and unresponsive to proton pump inhibitor therapy for at least 8 weeks, among other criteria.
At baseline, the mean age of patients in the higher-exposure dupilumab group was 6.8 years, 24.3% were girls, and 86.5% were white. Among the placebo patients, mean age was 7.2 years, 26.5% were girls, and 88.2% were white. The mean duration of EoE was 3.8 years in the intervention group and 4.4 years in the placebo group.
The dosing level of dupilumab was dynamic, depending on the initial size of the children and their growth. Those who were assigned to higher-exposure dupilumab were designated for that treatment at baseline, but the placebo group didn’t get the active treatment until after 16 weeks.
The incidence of adverse events during the treatment period was 73% to 100% across the trial groups and trial parts. Most adverse events were mild or moderate in both groups.
The study was supported by Sanofi and Regeneron.
Chehade disclosed relationships with Adare Pharma Solutions/Ellodi, Allakos, AstraZeneca, Bristol Myers Squibb, Nexstone Immunology, Phathom, Recludix Pharma, Regeneron Pharmaceuticals, Sanofi, and Shire/Takeda.
Shah disclosed relationships with Lupin.
American College of Gastroenterology
Source Reference: Chehade M, et al “Dupilumab improves histologic, endoscopic, and transcriptomic aspects of eosinophilic esophagitis (EoE) in children aged 1 to <12 years” ACG 2023.