Dupixent Demonstrates Disease-Modifying Effects in Eosinophilic Esophagitis Phase 4 Trial
核心洞察
Dupixent showed a 1.30 mm placebo-corrected improvement in esophageal distensibility at 24 weeks, equivalent to the benefit achieved by esophageal dilation procedures.
The drug significantly reduced disease-related structural changes with a 4.96-point placebo-corrected reduction in EREFS endoscopic scores and achieved 59% histological remission versus 4% with placebo.
The REMODEL trial establishes a new evidentiary standard using objective biomechanical measures of luminal compliance rather than symptom-based endpoints.
Dupixent (dupilumab) demonstrated significant improvements in esophageal function and structural changes in adults with eosinophilic esophagitis (搜索) (EoE (搜索)), achieving functional gains equivalent to mechanical dilation procedures through pharmacological intervention alone, according to results from the REMODEL Phase 4 trial presented at Digestive Disease Week 2026.
The randomized, double-blind, placebo-controlled trial enrolled 69 adults with EoE (搜索), with participants receiving either Dupixent 300 mg weekly (n=46) or placebo (n=23) for 24 weeks. The study's primary endpoint measured changes in esophageal distensibility plateau using endoluminal functional lumen imaging probe (EndoFLIP), an innovative approach to assess esophageal function based on scarring and narrowing.
Functional and Structural Improvements
Dupixent achieved a 1.28 mm improvement in esophageal distensibility plateau from baseline compared to -0.01 mm with placebo, representing a 1.30 mm placebo-corrected improvement (p<0.05). This translated to a 9% improvement from baseline compared to 1% with placebo, yielding an 8% placebo-corrected improvement (p<0.05).
"The magnitude of this improvement corresponded to the benefit that could be seen from an esophageal dilation procedure," said Evan S. Dellon, M.D., M.P.H., Professor of Gastroenterology and Hepatology at the University of North Carolina School of Medicine and lead author of the study. "Dupixent showed a potential to modify the course of eosinophilic esophagitis (搜索) – by improving esophageal size at just 6 months."
The drug demonstrated substantial reductions in disease-related structural changes, with a 4.89-point reduction from baseline in abnormal endoscopic findings as assessed by EREFS (EoE (搜索) Endoscopic Reference Score) compared to a 0.07-point increase with placebo, yielding a 4.96-point placebo-corrected reduction (p<0.0001). The EREFS scale evaluates esophageal edema, rings, exudates, furrows, and strictures on a 0-18 scale.
Histological Remission and Cellular Changes
Dupixent achieved notable improvements in histological outcomes, with 59% of patients reaching peak esophageal intraepithelial counts of ≤6 eosinophils per high-power field (eos/hpf) compared to 4% with placebo (p<0.0001). Additionally, 78% of patients achieved counts below the 15 eos/hpf diagnostic threshold for EoE (搜索) compared to 4% with placebo.
The drug also demonstrated improvements in disease severity and extent as measured by EoE (搜索) Histology Scoring System (EoE-HSS) grade and stage scores, with 0.89-point and 0.80-point reductions from baseline, respectively, compared to 0.18-point and 0.14-point reductions with placebo (0.71-point and 0.65-point placebo-corrected reductions; p<0.0001 for both).
Safety Profile
The safety results were generally consistent with Dupixent's known profile in EoE (搜索). Overall adverse event rates were 62% for Dupixent versus 48% for placebo. The most common adverse events with Dupixent included injection site pain (9% vs. 4% with placebo) and headache (9% vs. 4%). No serious adverse events occurred in either treatment group.
Clinical Significance and Disease Modification
The trial results provide evidence that IL-4 (搜索) and IL-13 (搜索) blockade can reverse fibroinflammatory remodeling processes in EoE (搜索) rather than merely suppressing surface inflammation. EoE is a chronic, progressive inflammatory disease that damages the esophagus and prevents proper function, often requiring mechanical dilation procedures when the esophagus narrows significantly.
"It also reduced hallmark endoscopic and histologic signs of disease, which further strengthens the evidence that type 2 inflammation plays an important role in the biology of this disease," Dellon noted.
The REMODEL trial establishes a new evidentiary standard by using objective biomechanical measures of luminal compliance as the primary endpoint, moving beyond traditional symptom-based assessments like dysphagia questionnaires. This approach captures actual tissue architecture changes rather than solely patient-reported experiences.
Ongoing Research
The trial continues through week 128 with an open-label treatment period where all participants, including those who received placebo, can receive Dupixent. Further assessments of esophageal distensibility are planned at weeks 76 and 128, which will provide insights into the durability and potential compounding effects of prolonged IL-4 (搜索)/IL-13 (搜索) suppression.
Dupixent, developed jointly by Regeneron and Sanofi, is a fully human monoclonal antibody that inhibits IL-4 (搜索) and IL-13 (搜索) signaling pathways. It was the first and remains the only biologic approved for EoE (搜索) treatment, having received regulatory approvals in more than 60 countries for various indications including atopic dermatitis (搜索), asthma (搜索), and chronic rhinosinusitis with nasal polyps (搜索).