Gastroenterology · Medical Literature
[Articles] Dupilumab versus placebo in adults and adolescents with eosinophilic gastritis (DEGAS): a double-blind, placebo-controlled, phase 2, multicentre, randomised controlled trial
Abstract
The improvement of histological outcomes of eosinophilic gastritis with dupilumab in this proof-of-concept study shows type 2 inflammatory involvement in the disease and the potential value of dupilumab for the treatment of eosinophilic gastritis.
Clinical relevance
In adults and adolescents with histologically active eosinophilic gastritis and moderate-to-severe symptoms, does dupilumab (anti–IL-4/IL-13 monoclonal antibody) reduce gastric eosinophil burden and improve histologic and endoscopic outcomes compared with placebo over 12 weeks? __SNAPSHOT__ {"studyDesign":"Proof-of-concept, phase 2, multicentre, double-blind, placebo-controlled randomised controlled trial (12-week double-blind period followed by a 24-week open-label extension); ClinicalTrials.gov NCT03678545","setting":"11 academic hospitals in the USA, all part of the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) within the NIH-supported Rare Diseases Clinical Research Network; enrollment May 2021–November 2023","sampleSize":"n=41 (dupilumab: n=21 [51%]; placebo: n=20 [49%]); all included in safety analysis","population":"Patients aged 12–70 years (mean age 30.5 years; 61% female) with histologically active eosinophilic gastritis defined as ≥30 eosinophils per high-power field (HPF) in at least five HPFs in the gastric antrum and/or body, plus moderate-to-severe symptoms occurring ≥2 days per week in the 2 weeks before screening. Patients with recent biologic use or systemic steroids >10 mg/day prednisone were excluded. Randomisation was stratified by age (12–17 vs ≥18 years) and concurrent corticosteroid or immunosuppressant use.","intervention":"Subcutaneous dupilumab: 600 mg loading dose at baseline, followed by 300 mg every 2 weeks (q2w) for 12 weeks (6 injections total); background EoG treatments and elimination diets were maintained throughout","comparator":"Subcutaneous placebo administered on the same schedule for 12 weeks; all placebo-arm patients crossed over to open-label dupilumab (600 mg loading dose then 300 mg q2w) at week 12","primaryOutcome":"Relative (percent) change from baseline in mean gastric eosinophil count at week 12","followUp":"12 weeks (double-blind phase) + 24 weeks open-label extension = 36 weeks total","fundingSource":"NIH (Rare Diseases Clinical Research Network / CEGIR); protocol reviewed by Regeneron Pharmaceuticals and Sanofi; multiple authors disclose Regeneron/Sanofi financial relationships"}
Key findings
Primary outcome: At week 12, dupilumab produced a 50% mean relative reduction in gastric eosinophil count versus a 4% reduction with placebo (between-group difference: −47 percentage points; p<0.001). The absolute eosinophil count difference, confidence intervals around the between-group estimate, and NNT for histologic response are not reported in the publicly available abstract or secondary sources; NNT cannot be calculated. Secondary outcomes: Dupilumab outperformed placebo on the Eosinophilic Gastritis Histologic Scoring System (EoG-HSS) total score, absolute change in mean gastric eosinophil count from the five most eosinophil-dense HPFs, and the Eosinophilic Gastritis Endoscopic Reference System (EoG-REFS) total score; specific values for these endpoints are not reported in the abstract. A post-hoc analysis also showed a greater proportion of dupilumab-treated patients had improvements in non-eosinophilic histopathology (EoG-HSS lamina propria smooth muscle hyperplasia component). Symptom scores did not differ significantly between groups at week 12. Tissue-level improvements observed at week 12 in the dupilumab group were sustained through week 36. The safety profile was consistent with the established dupilumab safety record across other approved indications; specific adverse event rates and serious adverse events are not reported in the abstract.
Practice implications
The DEGAS trial establishes proof-of-concept that IL-4/IL-13 blockade with dupilumab produces statistically significant and directionally large improvements in objective gastric histologic and endoscopic measures in EoG—a disease with no FDA-approved pharmacotherapy. The magnitude of the primary outcome (50% vs 4% eosinophil reduction, p<0.001) is clinically meaningful in the context of a disease defined by eosinophilic tissue infiltration. However, several critical limitations constrain interpretation: (1) Symptom scores, the patient-relevant outcome, did not significantly differ between groups; the authors appropriately attribute this to the absence of validated symptom instruments for EoG rather than true symptom equivalence, but the dissociation between tissue and clinical improvement remains unresolved. (2) Treatment goals—specifically the eosinophil threshold that constitutes histologic remission in EoG—have not yet been defined, limiting clinical translation of these histologic findings. (3) The open-label extension lacks an active placebo arm, so durability data at 36 weeks are uncontrolled. (4) This was an investigator-initiated trial within a rare-disease academic network; findings apply to patients resembling the enrolled population (moderate-to-severe, histologically confirmed EoG at U.S. academic centres). Only available as a published abstract for independent critical appraisal at the time of this summary, though the full article is published in Lancet Gastroenterology & Hepatology. Dupilumab is not FDA-approved for EoG. The authors and the Rare Diseases Clinical Research Network indicate there is now rationale for off-label use while a larger registration trial is planned. __LIMITATIONS__ Very small sample size (n=41 total; n=21 dupilumab), severely limiting statistical power for subgroup analyses, adverse event detection, and generalizability.,Short double-blind period (12 weeks) is insufficient to assess durability of response or long-term safety in a chronic relapsing disease.,Primary and key secondary endpoints are histologic/endoscopic surrogates; validated patient-reported symptom outcome measures for EoG do not exist, and symptom scores did not differ significantly between groups.,Histologic remission thresholds for EoG are not established, making clinical interpretation of eosinophil-count reductions uncertain.,Open-label extension (weeks 12–36) is uncontrolled; efficacy data from this period cannot be causally attributed to dupilumab due to absence of a comparator arm.,Conducted exclusively at U.S. academic CEGIR-affiliated centres with expertise in EGIDs; results may not generalise to community gastroenterology practice.,Multiple co-investigators have disclosed financial relationships with Regeneron Pharmaceuticals and Sanofi (manufacturers of dupilumab), though the trial was NIH-investigator-initiated.,Adolescents (ages 12–17) were included as a separate stratification stratum; age-specific efficacy and safety data are not reported separately in the abstract.,Post-hoc nature of the lamina propria smooth muscle hyperplasia analysis requires independent confirmation.,Only abstract-level data reviewed; full data tables, confidence intervals, and adverse event details require review of the complete publication. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ The DEGAS trial provides the first randomised evidence that dupilumab reduces gastric eosinophilic inflammation in EoG, with a 50% vs 4% relative eosinophil reduction (p<0.001) and concordant improvements in endoscopic and histologic scoring. Symptom outcomes did not differ significantly between groups, validated EoG symptom tools are lacking, and histologic treatment targets remain undefined, precluding definitive conclusions about clinical benefit. This is a hypothesis-confirming phase 2 proof-of-concept study; current evidence does not yet support routine use of dupilumab for EoG, but provides sufficient mechanistic and signals-based justification for a larger, adequately powered registration trial.