Therapies Targeting Eosinophils Expand Options for Eosinophilic Gastrointestinal Disorders
Key Clinical Summary
- Eosinophilic gastrointestinal disorders (EGIDs), including eosinophilic esophagitis (EoE) and non-EoE EGIDs, appear to be increasing in prevalence and remain underdiagnosed; mortality is not increased in EoE but is higher in gastric and small intestinal EGIDs.
- Current evidence-based EoE therapies include proton pump inhibitors, swallowed topical corticosteroids, dietary elimination, and dupilumab targeting IL-4/IL-13 signaling, while treatment of non-EoE EGIDs relies largely on dietary therapy and corticosteroids because randomized trial data remain limited.
- Emerging biologics targeting IL-13, IL-5, IL-2, IL-15 receptor pathways, along with new corticosteroid formulations and dupilumab for eosinophilic gastritis, are under investigation as potential future treatment options.
Eosinophilic gastrointestinal disorders (EGIDs) are increasingly recognized as underdiagnosed, immune-mediated diseases that extend beyond eosinophilic esophagitis (EoE), according to a comprehensive review published in the Journal of Gastroenterology and Hepatology. The review highlights advances in eosinophil-targeted therapies while emphasizing persistent evidence gaps for nonesophageal EGIDs.
The review, authored by investigators from the University of Newcastle and affiliated Australian institutions, summarizes current pharmacologic and dietary therapies for eosinophilic gastrointestinal disorders, ranging from eosinophilic esophagitis to eosinophilic gastritis, duodenitis, enteritis, and colitis. The authors also examine the epidemiology, diagnosis, pathophysiology, and evolving therapeutic landscape of these disorders.
Study Findings
The authors note that EGIDs encompass eosinophilic esophagitis (EoE) and non-EoE disorders affecting the stomach, small intestine, and colon. Although EoE is the best-characterized condition, non-esophageal EGIDs are increasingly recognized but remain comparatively understudied. EoE does not appear to increase mortality, the investigators found, although gastric and small intestinal EGIDs are associated with increased mortality.
For EoE, randomized clinical trials support several established treatment options, including proton pump inhibitors, swallowed topical corticosteroids, dietary restriction, and dupilumab, which inhibits IL-4 and IL-13 signaling. These therapies effectively reduce eosinophilic inflammation, although improvement in symptoms may not always parallel histologic remission, suggesting that disease mechanisms extend beyond eosinophilic infiltration alone.
Management of non-EoE EGIDs remains more challenging because randomized evidence is scarce. Current practice relies primarily on dietary elimination strategies combined with corticosteroids or immunomodulators. The review also notes that mast cell stabilizers and antihistamines may play a therapeutic role in selected patients, although evidence remains limited, and the value of combination therapy is not yet established.
The authors describe an expanding pipeline of investigational therapies, including novel corticosteroid preparations and delivery systems, dupilumab for eosinophilic gastritis, and monoclonal antibodies targeting IL-13, IL-5, IL-2, and IL-15 receptor pathways. These approaches aim to improve disease control while expanding treatment options beyond corticosteroids.
Clinical Implications
The review underscores that EGIDs are frequently underrecognized, with some patients initially misclassified as having disorders of gut-brain interaction, such as irritable bowel syndrome or functional dyspepsia. Improved awareness of disease presentation, combined with appropriate histologic evaluation, may facilitate earlier diagnosis and more targeted management.
The authors also emphasize that reductions in tissue eosinophils do not consistently translate into symptom improvement, highlighting the complexity of disease pathogenesis and suggesting that additional inflammatory pathways contribute to clinical manifestations. This observation supports continued investigation of therapies directed at multiple immune mechanisms rather than eosinophils alone.
For clinicians, current evidence supports established therapies for EoE, whereas treatment decisions for non-EoE EGIDs continue to rely on limited evidence and individualized management. Ongoing clinical trials of biologic agents may help address this unmet need and refine future treatment algorithms.
Expert Commentary
The review authors conclude that “targeted drug therapy can markedly reduce eosinophil infiltration, although symptom response is more variable, suggesting that non-eosinophil pathways play a role in pathogenesis." They further highlight that current EoE therapies are supported by randomized trials, whereas management of non-EoE EGIDs remains constrained by limited clinical evidence.
Reference: Batkhurel K, Prasad S, Potter M, Martin JH, Keely S, Talley NJ. Therapies targeting mucosal eosinophils in eosinophilic gut diseases from esophagus to colon. J Gastroenterol Hepatol. 2026; 41(2):606-624. https://doi.org/10.1111/jgh.70221
