August 05, 2026
3 min read
Key takeaways:
- Dupilumab reduced gastric eosinophil counts by an estimated 50% at 12 weeks compared with a 4% reduction with placebo.
- Results suggest eosinophilic gastritis is driven, at least in part, by type 2 inflammation.
Dupilumab significantly reduced gastric eosinophilic inflammation — and improved measures of endoscopic and histologic disease — at 12 weeks compared with placebo in patients with eosinophilic gastritis, according to phase 2 trial results.
Findings provide additional evidence that eosinophilic gastritis (EoG), which has no FDA-approved treatments, appears driven by the same immune pathways as eosinophilic esophagitis and other allergic diseases.
“Historically, clinicians have relied on dietary elimination strategies or corticosteroids, both of which have important limitations, particularly for long-term management,” Marc E. Rothenberg, MD, PhD, director of the Cincinnati Center for Eosinophilic Disorders, told Healio. “A major motivation for the trial was the growing body of evidence showing that EoG is a type 2 inflammatory disease.”
Prior studies have shown increased interleukin-4- and IL-13-associated immune responses in patients with EoG.
“Since dupilumab blocks signaling through the IL-4 and IL-13 pathways and had already demonstrated efficacy in eosinophilic esophagitis, we hypothesized that it could also be effective in eosinophilic gastritis,” Rothenberg said.
Rothenberg and colleagues conducted a proof-of-concept, multicenter, randomized controlled trial to investigate.
They randomly assigned 41 patients aged 12 to 59 years (mean age, 30.5 years; 61% female; 90% white) with histologically active EoG to placebo (n = 20) or a one-time 600 mg dose of dupilumab (Dupixent; Regeneron, Sanofi) followed by 300 mg biweekly (n = 21) for a total of six injections over 12 weeks.
Thirty-seven patients then participated in an unblinded, 24-week, open-label extension period.
Relative change from baseline in mean gastric eosinophil count, an indicator of inflammation, served as the primary endpoint. Secondary endpoints included changes in endoscopic and histologic severity scores.
Patients treated with dupilumab experienced an estimated 50% reduction (95% CI, –66 to –34) in mean gastric eosinophil count at week 12 compared with a 4% drop (95% CI, –20 to 13) in the placebo group.
Absolute changes from baseline also were greater in the dupilumab group for EoG Histologic Scoring System (EoG-HSS) total score (–0.12 vs. –0.01 points), mean gastric eosinophil count (–36 vs. –3.2 eosinophils/HPF) and EoG Endoscopic Reference System (EoG-REFS) total score (–3.47 vs. –0.06 points).
“Taken together, these findings provide strong evidence that targeting the IL-4/IL-13 pathway can effectively improve objective measures of eosinophilic gastritis and support the concept that EoG shares key disease mechanisms with eosinophilic esophagitis and other type 2 inflammatory disorders,” Rothenberg said.
Incidence of adverse events at week 12 was similar between dupilumab and placebo groups (81% vs. 85%), with blood eosinophilia being the most common treatment-emergent event (29% vs. 30%).
“Dupilumab was generally well tolerated in this trial, with no serious adverse events or treatment-related deaths reported,” Rothenberg added.
Researchers did not include symptom improvement as a coprimary outcome, as no validated tool to assess EoG symptoms exists. However, participants’ EoG Symptom Questionnaire eDiary scores revealed no significant change from baseline in either group.
Improvements in mean gastric eosinophil count and EoG-HSS and EoG-REFS scores were sustained through 36 weeks among participants who continued in the open-label extension portion of the trial.
Rothenberg and colleagues postulate that more frequent dosing over a longer period might improve EoG symptoms.
A crucial limitation of this trial is its small sample size. Large-scale trials that consider patient subgroups, based on disease characteristics, are necessary, according to the researchers.
“Although additional studies are needed, these findings represent an important step toward targeted, mechanism-based therapy for a disease that currently has no approved treatments,” Rothenberg said.
For more information:
Marc E. Rothenberg, MD, PhD, is director of the Cincinnati Center for Eosinophilic Disorders and the division of allergy and immunology at Cincinnati Children’s and professor in the department of pediatrics at University of Cincinnati. He can be reached at marc.rothenberg@cchmc.org.
Sources/Disclosures
Source:
Gonsalves NP, et al. Lancet Gastroenterol Hepatol. 2026;doi.org/10.1016/S2468-1253(26)00116-0.
Disclosures:
Rothenberg reports consulting roles with AstraZeneca, Bristol Myers Squibb, Celgene, Celldex, EnZen Therapeutics, Guidepoint, Regeneron, Sanofi, Santa Ana Bio and Uniquity Bio; educational grants from AstraZeneca, CURED Foundation, Food Allergy Fund, GSK, NIH, Regeneron/Sanofi and U.S.-Israel Binational Science Foundation; royalties or licenses from Ception Therapeutics, Mapi Research Trust and UpToDate; stock or stock options in Allakos, Celldex, ClostraBio, EnZen Therapeutics, PulmOne, Santa Ana Bio, Serpin Pharm, Spoon Guru and Uniquity Bio; and leadership or fiduciary roles with Food Allergy Research & Education and International Eosinophil Society. Please see the study for all other authors’ relevant financial disclosures.
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