Dupilumab Shows Histologic Benefit in Eosinophilic Gastritis Trial

Key Takeaways

• Dupilumab was associated with greater week 12 improvement in the primary gastric histologic endpoint than placebo.
• Prespecified secondary histologic and endoscopic measures, including EoS-HSS, mean gastric eosinophil count, and EoG-REFS, also favored dupilumab.
• Treatment-emergent adverse events were similar in both groups, blood eosinophilia was most common, and no serious adverse events or treatment-related deaths were reported.

In the DEGAS phase 2 trial, dupilumab produced a 47 percentage-point greater reduction in mean gastric eosinophil count at week 12 than placebo in adults and adolescents with eosinophilic gastritis. The randomized, placebo-controlled comparison also showed similar overall rates of treatment-emergent adverse events across groups.

DEGAS was a proof-of-concept, multicentre, phase 2 randomised controlled trial with a 12-week double-blind, placebo-controlled period followed by a 24-week open-label extension. Patients aged 12-70 years needed at least 30 eosinophils per high-power field in at least five high-power fields in the gastric antrum and/or body, plus moderate-to-severe symptoms at least 2 days weekly. Patients were randomised 1:1 to dupilumab 600 mg once, then 300 mg every 2 weeks, or placebo, over six injections. Stratification used age and use of systemic corticosteroids, swallowed corticosteroids, or non-steroidal systemic immunosuppression, and treatments or diets were maintained. The primary endpoint was relative change in mean gastric eosinophil count from the five most eosinophil-dense HPFs at week 12.

Among 41 randomized patients aged 12-59 years, 21 received dupilumab and 20 placebo; one placebo patient withdrew before week 12, leaving efficacy data for 21 and 19 patients. At week 12, estimated mean change in the primary endpoint was -50% with dupilumab (95% CI, -66 to -34) and -4% with placebo (95% CI, -20 to 13). The between-group difference was -47 percentage points (95% CI, -70 to -24; p<0.0001). Secondary differences were -0.10 for EoS-HSS (95% CI, -0.18 to -0.03; p=0.0055) and -38.8 for mean gastric eosinophil count (95% CI, -75.6 to -17.8; p=0.0008). The EoG-REFS total score difference was -3.42 (95% CI, -6.18 to -0.65; p=0.016), all at the prespecified week 12 analysis.

Treatment-emergent adverse events occurred in 17 of 21 patients (81%) with dupilumab and 17 of 20 patients (85%) with placebo. Blood eosinophilia was the most common adverse event, occurring in 6 of 21 patients (29%) and 6 of 20 patients (30%), respectively. No serious adverse events or treatment-related deaths were reported.