The Trial
Conducted at one Canadian and 26 US sites, the two-part phase 3 study randomly assigned 102 EoE patients aged 1-11 years who were refractory to proton pump inhibition in a 2:2:1:1 ratio.
Part A enrolled 102 patients and evaluated dupilumab at a weight-tiered higher-dose or lower-dose regimen vs placebo (two groups) for 16 weeks.
Part B was a 36-week extended active treatment period in which eligible dupilumab recipients from part A maintained their weight-tiered higher- or lower-dose regimen, whereas those in the placebo groups switched to weight-tiered higher- or lower-dose dupilumab.
The primary end point was histologic remission (peak esophageal intraepithelial eosinophil count, ≤ 6 per high-power field) at week 16. Continued dupilumab treatment appeared to maintain its effect through week 52.
During part A, histologic remission occurred in 25 of the 37 higher-exposure patients (68%), 18 of the 31 lower-exposure patients (58%), and one of the 34 placebo patients (3%).
The difference between the higher-exposure regimen and placebo was 65 percentage points (95% confidence interval [CI], 48-81; P < .001), whereas that between the lower-exposure regimen and placebo was 55 percentage points (95% CI, 37-73; P < .001).
Higher exposure led to significant improvements in histologic, endoscopic, and transcriptomic measures over placebo. Improvements between baseline and week 52 in all patients were generally similar to those between baseline and week 16 in patients who received dupilumab in part A.
As for adverse events, in part A, the incidence of coronavirus disease, nausea, injection-site pain, and headache was at least 10 percentage points higher among dupilumab recipients at either dose than among placebo recipients. Serious adverse events were reported in three dupilumab patients during part A and in six patients overall during part B.
A Balanced Approach
On a cautionary note, Eric H. Chiou, MD, an assistant professor of pediatrics at Baylor College of Medicine and a pediatric gastroenterologist at Texas Children’s Hospital in Houston, said that while dupilumab shows great promise, further research is needed on its cost-effectiveness in EoE.
“The cost of treatment will need to be compared relative to potential long-term savings from reduced hospitalizations, fewer complications, and improved quality of life,” said Dr. Chiou, who was not involved in the study. “A balanced approach that considers clinical efficacy, patient well-being, cost-effectiveness, and equity is essential.”
Dr. Eric H. Chiou
He added that despite the study’s encouraging results, long-term safety and efficacy data are needed to fully understand the impact of dupilumab on pediatric patients with EoE. “Dupilumab will need to be compared with existing treatments for EoE such as dietary management and swallowed topical corticosteroids in terms of efficacy, safety, and quality of life improvements.”
Additionally, further research is required to identify which patients are most likely to benefit from this therapy and to explore any potential complications associated with its long-term use. “Understanding the optimal dosing and duration of treatment will also be crucial for maximizing benefits while minimizing risks,” Dr. Chiou said.
Dr. Chehade agreed. “While it’s that great that young children finally have an FDA-approved drug to treat their EoE, more research is needed to learn which patient subsets would derive maximum benefit from dupilumab and at which specific steps in their medical management journey should dupilumab be used.”
This study was supported by Sanofi and Regeneron Pharmaceuticals. Dr. Chehade disclosed research funding from and consulting for numerous private sector companies, among others, Sanofi and Regeneron Pharmaceuticals, AstraZeneca, Shire-Takeda, and Bristol-Myers Squibb. Multiple study coauthors disclosed various relationships with private-sector companies, including Sanofi and Regeneron Pharmaceuticals, for research funding, consulting, travel, employment, and stock or intellectual ownership. Dr. Webster and Dr. Chiou disclosed no competing interests relevant to their comments.
A version of this article first appeared on Medscape.com.