Dupilumab Shows Significant Tissue-Level Improvements in Phase 2 Trial for Eosinophilic Gastritis
核心洞察
The phase 2 DEGAS trial found dupilumab significantly reduced stomach eosinophil counts and improved endoscopic and histologic outcomes in patients with eosinophilic gastritis (搜索) over 12 weeks, with benefits sustained through 36 weeks.
The 11-center study, published in The Lancet Gastroenterology & Hepatology, involved 41 adolescents and adults and was conducted by the NIH-supported CEGIR (搜索) consortium led by Cincinnati Children's.
No FDA-approved medications currently exist for EoG, a rare inflammatory food-allergic disease affecting an estimated 5 to 7 per 100,000 people, leaving patients reliant on strict food-elimination diets.
A phase 2 clinical trial published June 23, 2026, in The Lancet Gastroenterology & Hepatology has demonstrated that the monoclonal antibody dupilumab produces significant tissue-level improvements in patients with eosinophilic gastritis (搜索) (EoG), a rare inflammatory food-allergic disease of the stomach for which no approved pharmacologic treatments exist.
The Dupilumab Eosinophilic Gastritis (搜索) Study (DEGAS), conducted across 11 U.S. medical centers by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR (搜索)), enrolled 41 adolescents and adults with active EoG. Participants were randomly assigned to receive either dupilumab or placebo for an initial 12-week period, after which all participants received dupilumab during an open-label extension.
Those receiving dupilumab during the double-blind phase showed improvements across multiple objective measures, including reduced stomach eosinophil counts, improved results from endoscopy exams, and improved scores on pathology of stomach tissue samples. These tissue-level improvements continued through 36 weeks, encompassing the period when all participants received the treatment during the extension phase. The safety profile observed was consistent with prior studies of dupilumab.
"For many rare diseases, the small numbers of people affected makes it extremely difficult for pharmaceutical companies to conduct the clinical studies needed to secure U.S. FDA approval," said Marc Rothenberg, MD, PhD, director of the Division of Allergy and Immunology at Cincinnati Children's and leader of the CEGIR (搜索) consortium. "But for some conditions, investigational evaluation of an already-approved therapy in a new, relevant disease setting can become a vital pathway to improved outcomes."
Disease burden and unmet need
Eosinophilic gastritis (搜索) is characterized by a surge in eosinophils — a type of white blood cell — within the stomach, triggering an inflammatory allergic response. Common food triggers include dairy, wheat, gluten, egg, soy, fish, and nuts. Flare-ups can cause nausea, vomiting, abdominal pain, and fatigue, while chronic feeding difficulties may lead to poor growth, anemia, and other complications.
The disease occurs in an estimated 5 to 7 people per 100,000, making it roughly 10 times less common than eosinophilic esophagitis (搜索) (EoE), which affects up to 500,000 people in the U.S. Currently, patients rely on strict, lifelong food-elimination diets as the primary management strategy, as no FDA-approved medications exist to slow the inflammatory allergic response in the stomach.
Mechanism and prior approvals
Dupilumab is a monoclonal antibody that blocks signaling from interleukin-4 (搜索) and interleukin-13 (搜索), key cytokines involved in type 2 inflammation. It was first approved for adult atopic dermatitis in 2017 and has since received approval for eight additional conditions, including EoE. Rothenberg and CEGIR (搜索) colleagues were deeply involved in the studies leading to dupilumab's initial approval for EoE in 2022, which was extended in 2024 to include children as young as 1 year old weighing at least 15 kg.
Expert perspectives
"These findings are important because the study not only evaluated a potential treatment for EoG, but also improved our understanding of the biological processes that drive the disease," said Nirmala Gonsalves, MD, Professor of Medicine at Northwestern University School of Medicine and co-lead author of the study alongside Evan Dellon, MD, MPH, Professor at University of North Carolina, Chapel Hill. "While this study focused on changes seen in stomach tissue, the results provide important groundwork for larger trials that can better assess symptoms and long-term effects."
Future directions
By confirming the role of type 2 immune signaling in EoG, the DEGAS trial helps clarify the focus for future research. The findings support continued study of targeted, immune-based approaches and raise questions about optimal dosing, treatment duration, and how tissue-level improvements relate to patient experience. The co-authors state their findings merit taking further steps to seek FDA approval.
"Ongoing and future studies will be critical for building on this work and translating biological insight into more clearly defined treatment goals for EoG," Rothenberg said.
The study was conducted as part of CEGIR (搜索), a collaboration within the NIH-supported Rare Diseases Clinical Research Network (RDCRN), supported through a collaboration between NCATS, NIAID, and NIDDK under grant number U54AI117804. Additional funding came from Regeneron Pharmaceutical Inc. (搜索), Sanofi, and the Mayo Clinic (Arizona). Rothenberg noted that this collaborative, investigator-initiated approach "could potentially serve as a model to address EoG and even more of the 7,000+ rare diseases out there that still need effective treatments."