REMODEL: Dupilumab Improves Esophageal Distensibility in EoE at 24 Weeks

Results from the randomized, double-blind phase of the phase 4 REMODEL trial indicate that dupilumab significantly improved esophageal distensibility in adults with active eosinophilic esophagitis (EoE) compared with placebo at 24 weeks.

The findings, which were presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, by Evan Dellon, MD, a professor of medicine and adjunct professor of epidemiology at the University of North Carolina School of Medicine in Chapel Hill, suggest that the IL-4/IL-13 pathway inhibitor not only addresses mucosal inflammation in EoE but also produces measurable improvements in a functional marker of fibrostenotic disease, a dimension of EoE pathology that has historically lacked dedicated therapeutic evidence.

“For patients who have eosinophilic esophagitis, if the disease remains untreated, it can progress to narrowing of the esophagus, more severe symptoms, such as food impaction, and the need for esophageal dilation,” Dellon said in a statement. “[Dupilumab] showed a potential to modify the course of eosinophilic esophagitis – by improving esophageal size at just 6 months – the magnitude of this improvement corresponded to the benefit that could be seen from an esophageal dilation procedure. 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. The ongoing study will allow us to learn the even longer-term impact of [dupilumab] on the scarring and narrowing of the esophagus in EoE.”

EoE affects an estimated 1 in 850 individuals in developed countries and is characterized by type 2 inflammatory infiltration of the esophageal mucosa that, when inadequately treated, can progress to subepithelial fibrosis, esophageal strictures, and narrowing sufficient to cause food impaction.

Despite the availability of dupilumab as an FDA-approved therapy for EoE since 2022 in patients 12 years and older, and extended in January 2024 to children as young as 1 year weighing at least 15 kg, prospective data directly assessing the drug's impact on esophageal remodeling and distensibility in a randomized, controlled design had been limited.

REMODEL Trial Design and Primary Endpoint

The REMODEL trial enrolled 69 adults with active EoE who were randomly assigned in a 2:1 ratio to dupilumab 300 mg once weekly subcutaneously (n = 46) or placebo (n = 23) for 24 weeks. Stratification was based on prior dilation history. Baseline demographic and disease characteristics were described as generally comparable across treatment groups.

The primary endpoint was the absolute change from baseline in the esophageal distensibility plateau (DP), measured using the endoluminal functional lumen imaging probe (EndoFLIP). The DP is defined as the narrowest fixed diameter, in millimeters, of the distal esophageal body in response to increasing volume and pressure. EndoFLIP quantifies esophageal compliance and has emerged as an objective tool for identifying fibrostenotic changes in EoE that may not be fully apparent on standard endoscopy or histology alone.

Hierarchical secondary endpoints included percent change from baseline in DP, followed by changes in the Endoscopic Reference Score (EREFS) and EoE Histologic Scoring System (EoEHSS) grade and stage scores at week 24. Safety was also assessed.

Distensibility and Structural Outcomes at Week 24

At 24 weeks, results showed dupilumab produced a statistically significant improvement in esophageal distensibility relative to placebo. The least squares mean (LSM) change from baseline in DP diameter was +1.28 mm (SE, 0.29) in the dupilumab group versus −0.01 mm (SE, 0.42) in the placebo group, yielding an LSM difference of 1.30 mm (95% CI, 0.31–2.29; P <.05). The LSM difference in percent change from baseline in DP also reached significance at 7.78% (95% CI, 1.13–14.43; P <.05) in favor of dupilumab.

A notable subgroup finding emerged among patients with abnormal baseline DP below 17 mm, a threshold generally considered indicative of meaningful fibrostenotic impairment. In this subset, the between-group difference was larger than in the overall population: dupilumab patients gained a mean of +1.76 mm while placebo patients declined by −0.49 mm (LSM difference, 2.25 mm; 95% CI, 0.75–3.75).

Improvements in endoscopic and histologic outcomes were also observed. The LSM difference in EREFS score favored dupilumab over placebo by −4.96 points (95% CI, −6.06 to −3.85; P <.0001). The EoEHSS grade and stage scores similarly improved: LSM differences were −0.71 (95% CI, −0.86 to −0.57; P <.0001) and −0.65 (95% CI, −0.80 to −0.51; P <.0001), respectively.

References

1. Dellon ES, Carlson DA, Greuter T, et al. DUPILUMAB IMPROVES ESOPHAGEAL DISTENSIBILITY IN ADULTS WITH EOSINOPHILIC ESOPHAGITIS: 24-WEEK RESULTS FROM THE RANDOMIZED, PLACEBO-CONTROLLED REMODELING WITH DUPILUMAB IN EOSINOPHILIC ESOPHAGITIS LONG-TERM (REMODEL) TRIAL. Presented at Digestive Disease Week (DDW) 2026; Chicago, IL; May 2–5, 2026.

2. Regeneron. Dupixent® (dupilumab) Demonstrates Improved Esophageal Function in Eosinophilic Esophagitis (EoE) Phase 4 Trial. May 5, 2026. Accessed May 5, 2026. https://newsroom.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-demonstrates-improved-esophageal-function