Dupilumab shows significant efficacy in achieving histologic remission in pediatric patients with eosinophilic esophagitis, highlighting potential for broader applications in managing type 2 inflammatory diseases.
Dupilumab, a monoclonal antibody targeting interleukin-4 and interleukin-13 pathways, demonstrated significant efficacy in inducing histologic remission in children with eosinophilic esophagitis (EoE) unresponsive to proton-pump inhibitors, according to a phase 3 trial. The study provides key insights into dosing regimens and safety profiles, emphasizing its potential use in clinical practice for managing pediatric EoE.
Study Design:
- Participants: Children aged 1 to 11 years with active eosinophilic esophagitis, unresponsive to proton-pump inhibitors.
- Groups: Patients were randomly assigned to higher-exposure or lower-exposure subcutaneous dupilumab regimens or placebo in a 2:2:1:1 ratio for 16 weeks (Part A).
- Continuation: After Part A, eligible patients continued their respective dupilumab regimens or were reassigned from placebo to dupilumab for an additional 36 weeks (Part B).
- Dosing: Dupilumab doses were tiered according to baseline body weight.
- Primary Endpoint: Histologic remission (peak esophageal intraepithelial eosinophil count, ≤6 per high-power field) at week 16.
- Secondary Endpoints: Tested hierarchically and included improvements in histologic, endoscopic, and transcriptomic measures.
Key Findings:
- Histologic Remission: Achieved in 68% of patients in the higher-exposure group, 58% in the lower-exposure group, and 3% in the placebo group.
- Differences: Higher-exposure regimen vs. placebo: 65 percentage points (95% CI, 48 to 81; P<0.001); Lower-exposure regimen vs. placebo: 55 percentage points (95% CI, 37 to 73; P<0.001).
- Improvements: Higher-exposure dupilumab led to significant improvements in histologic, endoscopic, and transcriptomic measures compared to placebo.
- Safety: Incidences of COVID-19, nausea, injection-site pain, and headache were at least 10 percentage points higher in the dupilumab groups than in the placebo group.
- Serious Adverse Events: Reported in 3 patients during Part A and 6 patients overall during Part B.
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HCN Medical Memo
The phase 3 trial of dupilumab in pediatric eosinophilic esophagitis demonstrates significant histologic remission and clinical improvements. In the future, dupilumab may be viewed as a viable option for managing children with EoE, especially those unresponsive to standard treatments. Monitoring for adverse events is crucial to ensure patient safety.
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