June 29, 2026

Rare Diseases Clinical Research Network (RDCRN)

Food allergies can sometimes trigger ongoing inflammation in the digestive tract and lead to serious chronic disease. In some rare gastrointestinal (GI) diseases, the immune system overreacts and attacks tissues in the GI tract. This can lead to long-term symptoms, tissue damage and problems with how organs function. Eosinophilic gastritis (EoG) — one rare GI disease — does not have any U.S. Food and Drug Administration (FDA)–approved treatments. People with EoG can experience chronic symptoms, such as vomiting, bloating, diarrhea, ulcers and GI bleeding. The broad range of symptoms also can make it hard to find treatments that work for all patients.

A new clinical trial conducted by the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) in NIH’s Rare Diseases Clinical Research Network (RDCRN) showed that dupilumab improved the health of patients with rare GI disease and showed promise for yielding a successful therapy. The researchers recently published their findings in The Lancet Gastroenterology and Hepatology.

CEGIR found in a previous study that food allergens play an important role in EoG. When people with EoG eat food that they are allergic to, inflammatory signals called IL-4 and IL-13 are released. These signals cause eosinophils (a type of inflammatory immune cell) to travel to the stomach, where they associate with damage. Earlier studies by other researchers tested various drugs for EoG, but none worked well enough to become an approved treatment. Although some drugs reduced tissue inflammation, many patients still had ongoing symptoms and tissue damage.

Dupilumab — the drug explored for EoG in this study — is an FDA-approved drug already used to treat conditions such as asthma and chronic obstructive pulmonary disease. Previous research showed that dupilumab blocks IL-4 and IL-13 signals to reduce inflammation. In 2022, FDA approved the drug to treat eosinophilic esophagitis (EoE), another rare Eosinophilic Gastrointestinal Diseases (EGID) where eosinophils attack the esophagus.

Nirmala Gonsalves, M.D., a principal investigator with CEGIR and professor of medicine at Northwestern University Feinberg School of Medicine, stated, “Genetic signatures between patients with EoE and EoG showed that there were several overlaps. It made sense to think about [dupilumab] as a potential therapeutic agent in EoG. There are no FDA-approved therapies, and this is a huge unmet need in our field.” Because dupilumab was already approved for related inflammatory diseases, researchers were able to quickly study whether the drug also could help patients with EoG.

In this multisite clinical trial, the CEGIR team found that dupilumab improved patient health compared with a placebo. The treatment reduced inflammation and improved tissue healing in the stomach lining. Stomach biopsies also showed a significant decrease in eosinophils, and the drug helped reverse harmful disease-related changes in the stomach. Patients also reported feeling better during treatment.

Marc E. Rothenberg, M.D., Ph.D., CEGIR principal investigator and director of the Cincinnati Center for Eosinophilic Disorders, stated, “This is key positive data, a precision therapy — dupilumab — for EoG.” Rothenberg added that specific disease-related gene patterns may help predict which patients are more likely to have a form of the disease that responds to the drug. This could help doctors develop more personalized treatment plans in the future.

Gonsalves underscored that collaborative efforts were critical for making the study possible. “This research highlights the importance of collaboration in achieving those outcomes,” she said. Because EoG is a rare disease, conducting a rigorous clinical trial required coordination across many specialized research centers through the RDCRN-supported CEGIR network. The clinical trial involved partnerships with health care providers and two companies in industry — Regeneron and Sanofi. Working with patient advocacy groups for eosinophilic disease — including the Campaign Urging Research for Eosinophilic Disease (CURED), American Partnership for Eosinophilic Disorders (APFED) and Eosinophilic Family Coalition (EFC) — during the clinical trial was vital as well. Researchers leveraged results from earlier research findings and feedback from the patient advocacy groups to help design the study.

This type of collaborative research is central to NCATS’ mission to speed the development of treatments and improve clinical trial readiness for rare diseases. The study also highlights how repurposing existing drugs may help researchers find new treatment options faster for patients with chronic diseases.

This clinical trial represents an important step forward for patients with EoG and reflects how RDCRN and CEGIR are advancing NIH priorities to improve treatments and health outcomes for people living with rare diseases. Tiina K. Urv, Ph.D., NCATS’ program director for the RDCRN, explains, “the work by RDCRN consortia, like CEGIR, demonstrate the importance of conducting strong foundational research that demonstrate both what works and what does not — this, along with rigorous research methods lead us to effectively finding paths to treatments for rare diseases.”

CEGIR is part of the RDCRN, which is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). CEGIR is funded under grant number U54AI117804 as a collaboration between NCATS, the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).