Professionals

Authors
Nirmala P Gonsalves et al.

Journal
The Lancet Gastroenterology & Hepatology. Published online June 23, 2026.
doi: 10.1016/S2468-1253(26)00116-0

Paper of the Month – Selected and discussed by Salvatore Oliva

🎯 Study Aim

The DEGAS trial evaluated the efficacy and safety of dupilumab in adolescents and adults with active eosinophilic gastritis (EoG), a rare eosinophilic gastrointestinal disease for which no approved pharmacological treatment is currently available. The study specifically investigated whether blocking IL-4 and IL-13 signalling could improve gastric eosinophilic inflammation, broader histopathological abnormalities, endoscopic findings, and symptoms.

🔬 Methods

This phase 2, multicentre, proof-of-concept trial enrolled 41 patients aged 12–70 years with symptomatic and histologically active EoG, defined as at least 30 eosinophils per high-power field in five or more gastric high-power fields. Participants were randomised 1:1 to receive subcutaneous dupilumab (600 mg loading dose followed by 300 mg every 2 weeks) or placebo for 12 weeks. All patients completing the double-blind period could subsequently receive dupilumab during a 24-week open-label extension.

The primary endpoint was the relative change from baseline to week 12 in the mean gastric eosinophil count across the five most eosinophil-dense high-power fields. Secondary outcomes included changes in the Eosinophilic Gastritis Histologic Scoring System (EoG-HSS), the Eosinophilic Gastritis Endoscopic Reference System (EoG-REFS), and the Eosinophilic Gastritis Symptom Questionnaire (EoG-SQ).

📊 Key Findings

At week 12, dupilumab produced a significantly greater reduction in gastric eosinophil counts than placebo: the estimated mean relative change was −50% with dupilumab versus −4% with placebo, corresponding to a between-group difference of −47 percentage points (p<0.0001).

Dupilumab also significantly improved overall histopathological severity, mean gastric eosinophil counts, and endoscopic abnormalities. Histopathological remission was observed in 24% of dupilumab-treated patients and 11% of placebo-treated patients. Improvements in objective outcomes were generally sustained through week 36, while patients who switched from placebo to dupilumab showed similar subsequent improvements.

However, despite a numerically greater reduction in symptom scores with dupilumab, the difference compared with placebo was not statistically significant. Adverse-event rates were similar between groups, and no serious adverse events or treatment-related deaths occurred.

🧠 Interpretation

This first randomised controlled trial of dupilumab in EoG provides direct evidence that IL-4- and IL-13-mediated type 2 inflammation plays a central role in the disease. Importantly, the benefits extended beyond eosinophil depletion, with improvements in structural histopathological features, endoscopic abnormalities, and molecular disease activity. This may distinguish upstream type 2 cytokine blockade from therapies directed exclusively at eosinophils.

Nevertheless, the absence of a significant symptomatic benefit highlights the persistent disconnect between biological disease activity and patient-reported symptoms in EoG. This could reflect the short treatment period, the every-2-week dosing regimen, irreversible or slowly reversible tissue remodelling, visceral hypersensitivity, or limitations of the symptom instrument itself.

⚠️ Critical Appraisal

The main strengths of the DEGAS study are its randomised, double-blind, placebo-controlled design; centralised assessment of gastric histology; and multidimensional evaluation incorporating histological, endoscopic, symptomatic, and transcriptomic outcomes.

However, this was a small proof-of-concept study involving only 41 patients, including seven adolescents, and it was powered only for the histological primary endpoint. The 12-week placebo-controlled period might have been too short to demonstrate symptomatic improvement, and the dupilumab regimen of 300 mg every 2 weeks was lower than the weekly regimen shown to improve symptoms in EoE. Moreover, the EoG-SQ has not yet been fully validated in a large population, baseline disease duration and concomitant EoE differed between treatment groups, and the open-label extension lacked a placebo comparator.

Therefore, these results demonstrate biological efficacy but do not yet establish the optimal dose, treatment duration, patient selection strategy, or clinical effectiveness of dupilumab in EoG.

📝 Take-Home Message

Dupilumab significantly improves gastric eosinophilic inflammation, broader histopathological abnormalities, and endoscopic disease activity in adolescents and adults with EoG, confirming the central role of IL-4 and IL-13 in its pathogenesis. However, the lack of a significant symptomatic advantage over placebo reminds us that histological response does not necessarily translate into rapid clinical benefit.

Larger and longer trials—particularly those evaluating weekly dosing and validated symptom measures—are needed to determine whether this promising biological effect can translate into meaningful and sustained benefits for patients.