TOPLINE

Treatment of eosinophilic esophagitis (EoE) in adults with the monoclonal antibody dupilumab, already approved for treatment of the condition, significantly improved esophageal diameter over 24 weeks compared with placebo, suggesting important benefits of the drug in esophageal remodeling.

The results indicate that dupilumab, with known improvements in esophageal histology and endoscopic severity, also appears to address a notable complication of EoE — the narrowing of the esophagus, which usually requires treatment with esophageal dilation.

METHODOLOGY

• In the phase 4 REMODEL trial, 69 adults with EoE were randomly assigned in a 2:1 ratio to treatment with dupilumab 300 mg once weekly (n = 46) or placebo (n = 23) for 24 weeks.
• Of the patients, 30 patients had a distensibility plateau at baseline < 17 mm, including 19 in the dupilumab group, and 11 in the placebo group.
• Nearly 33 patients had a distensibility plateau at baseline ≥ 17 mm, including 22 vs 11 in the dupilumab group vs the placebo group. The remaining six patients were not categorized due to missing data.
• The baseline characteristics were similar between the two groups.

TAKEAWAY

• At week 24, for the primary outcome, patients treated with dupilumab had a significantly greater change from baseline esophageal distensibility plateau than those receiving placebo (least squares mean [LSM] change from baseline +1.28 mm vs -0.01 mm; LSM difference, +1.30 mm; P < .05).
• The degree of distensibility plateau improvement was greater in the subgroup of patients with a distensibility plateau < 17 mm at baseline, which is indicative of a decreased esophageal caliber (LSM difference, +2.21 mm; nominal P = .0024 vs +0.38 mm, nominal P = .5918).
• The change from baseline at week 24 in measures in the EoE Endoscopic Reference Score (EREFS) was significantly greater with dupilumab than with placebo (LSM difference, -4.96; P < .0001), including for the fibrostenotic subscore (LSM difference: -0.78; P = .018).
• The greater improvement in EREFS with dupilumab compared with placebo was consistent across subgroups (total score LSM difference, -5.13 and -4.90; both nominal P < .0001).
• No new safety signals were identified compared with previous findings.

IN PRACTICE

“This is the first randomized trial in EoE to use esophageal diameter (as measured by EndoFLIP) as a primary outcome in order to assess the effect of dupilumab vs placebo on esophageal remodeling,” the authors of the study reported in an American College of Gastroenterology press statement.

The gain observed in esophageal diameter with dupilumab was notable because “esophageal dilation was not allowed during the study, and yet the gain in esophageal diameter with dupilumab versus placebo was what could be gained in a dilation session,” the authors noted.

“Together, these findings suggest dupilumab is effective across the fibrostenotic-to-inflammatory spectrum of EoE,” said first author Evan S. Dellon, MD, MPH, professor of medicine and adjunct professor of epidemiology, Center for Esophageal Diseases and Swallowing, University of North Carolina at Chapel Hill, in presenting the findings.

SOURCE

Dellon presented the findings at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting in Nashville, Tennessee. The study was also published in The American Journal of Gastroenterology.

LIMITATIONS

Limitations include the relatively short follow-up period of 24 weeks. Because fibrosis is typically slow to evolve, “some of the observed esophageal distensibility plateau diameter improvements may reflect reduced inflammation rather than true remodeling,” the authors noted in the published study. Furthermore, distensibility was assessed only in the distal esophagus, not in the esophagogastric junction or proximal esophagus.

DISCLOSURES

Dellon reported consulting for and/or having other relationships with AbbVie; Adare Pharmaceuticals, Inc./Ellodi Pharmaceuticals; Alfasigma Global; Amgen; AnaptysBio, Inc.; Apogee Therapeutics; Apollo Therapeutics; Aqilion; Arena Pharmaceuticals/Pfizer; AstraZeneca; Bethanamist, Inc.; BioCryst Pharmaceuticals; Bryn Pharma; Calypso Biotech; Celgene/Receptos/Bristol Myers Squibb; Celldex Therapeutics; Cyted Health; Domain Therapeutics; Dr. Falk Pharma; EsoCap Biotech; Eupraxia Pharmaceuticals Inc., Ferring Pharmaceuticals; GI Reviewers; GSK; Holoclara; Invea; Knightpoint; Kymera Therapeutics; LucidDx; Meritage Pharma; Miraca Life Sciences; Nexstone Immunology/Uniquity Bio; Nutricia; Parexel/Calyx; Phathom Pharmaceuticals; Regeneron; Revolo; Robarts Clinical Trials/Alimentiv; Roivant; Sanofi; Takeda; Target RWE; Third Harmonic Bio; Uniquity; Upstream Bio.