Dupilumab Improves Esophageal Distensibility in EoE, With Evan Dellon, MD, MPH

Eosinophilic esophagitis (EoE) is a progressive, fibrostenotic disease, and managing inflammation alone may not be enough to prevent the structural complications that drive the greatest morbidity in affected patients.

New 24-week data from the phase 4 REMODEL trial presented at Digestive Disease Week (DDW) 2026 in Chicago, IL, provide the first randomized, controlled evidence that dupilumab can meaningfully improve esophageal distensibility, offering clinicians a potential tool not just for disease control, but for modifying the underlying remodeling process.

The findings were presented by Evan Dellon, MD, MPH, a gastroenterologist and professor of medicine at the University of North Carolina School of Medicine.

“It's been shown previously that if you have a more stiff esophagus, or the distensibility plateau that we measure, it's a more complicated term for essentially esophageal diameter, and as that goes down, you have a higher chance of food impaction and ER visit and needing dilation,” Dellon told HCPLive. "If you get the disease under control with some prior data on steroids or diet elimination, or even PPIs, you could increase that esophageal diameter and you are decreasing complication risks and need for dilation down the road.”

Study Design

REMODEL is a randomized, placebo-controlled phase 4 trial evaluating the effects of dupilumab on esophageal structure and function in adults with active EoE. A total of 69 patients were randomly assigned in a 2:1 ratio to dupilumab 300 mg once weekly or placebo. The primary endpoint was absolute change from baseline in the esophageal distensibility plateau (DP), measured by endoluminal functional lumen imaging probe (EndoFLIP) as the narrowest fixed diameter of the distal esophageal body, at week 24. Hierarchical secondary endpoints included endoscopic and histologic outcomes assessed by the Endoscopic Reference Score (EREFS) and EoE Histologic Scoring System (EoEHSS).

Key Findings

At week 24, dupilumab produced a statistically significant improvement in esophageal distensibility compared with placebo. The least squares mean change from baseline in DP diameter was +1.28 mm with dupilumab versus −0.01 mm with placebo, yielding a between-group difference of 1.30 mm (95% CI, 0.31–2.29; P <.05). In the subgroup of patients with abnormal baseline DP below 17 mm, those with the greatest degree of esophageal narrowing and the highest clinical risk, the treatment benefit was substantially larger, with a between-group difference of 2.25 mm.

Dellon highlighted the placebo arm's trajectory in this subgroup as particularly telling: those patients experienced a 0.5 mm decrease in esophageal diameter over just 6 months, providing direct evidence of ongoing structural progression in untreated disease.

"That's the progression I was talking about," he said. "If you were just using your eyes, there's no way you would detect that.”

Endoscopic and histologic improvements were also significant, with dupilumab producing meaningful reductions in EREFS and EoEHSS grade and stage scores compared with placebo (both P <.0001). No serious adverse events or deaths occurred in either arm.

Clinical Implications

Dellon noted that EndoFLIP remains primarily a research and specialized clinical tool, though its precision in measuring esophageal caliber makes it particularly valuable for identifying subtle narrowing not visible on standard endoscopy. He framed the REMODEL findings as an important step toward understanding whether treating EoE aggressively and early can alter the disease's natural history, not just manage its symptoms.

Editor's note: Dellon reports relevant disclosures with AbbVie, Alfasigma, AstraZeneca, Ferring, GSK, Phathom, Regeneron Pharmaceuticals Inc., Sanofi, Shire/Takeda, Target RWE, and others.

References

1. Brooks A. REMODEL: Dupilumab Improves Esophageal Distensibility in EoE at 24 Weeks. HCPLive. May 5, 2026. Accessed May 7, 2026. https://www.hcplive.com/view/remodel-dupilumab-improves-esophageal-distensibility-in-eoe-at-24-weeks

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