Benralizumab Completely Depletes Gastrointestinal Tissue Eosinophils and Improves Symptoms in Eosinophilic Gastrointestinal Disease

Fei Li Kuang*, Michelly Sampaio De Melo, Michelle Makiya, Sheila Kumar, Thomas Brown, Lauren Wetzler, Jean Anne M. Ware, Paneez Khoury, Margaret H. Collins, Martha Quezado, Stefania Pittaluga, Amy D. Klion

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Previous studies of targeted eosinophil biologics in eosinophilic esophagitis have yielded mixed results. Possible explanations include incomplete eosinophil depletion with anticytokine (anti–IL-5) treatments and/or irreversible fibrotic tissue changes contributing to symptomatology. Objective: To characterize the therapeutic effect of eosinophil depletion in patients with hypereosinophilic syndrome with varied eosinophilic gastrointestinal (GI) disorders. Methods: Hematologic, histologic, endoscopic, and clinical symptoms for a subset (n = 7) of hypereosinophilic syndrome patients with GI tissue eosinophilia enrolled in a phase 2 clinical trial of benralizumab (anti–IL-5RA) were assessed before and after treatment (NCT02130882). Results: Blood and GI tissue eosinophils were completely depleted in all segments of the GI tract, and all patients reported improved GI symptoms, in some cases as early as after the first monthly dose. Some patients had recurrent symptomatic flares without recurrent peripheral or tissue eosinophilia, in most cases after prolonged symptomatic remission and in the setting of liberalization of dietary restrictions and/or tapering of background therapy. Although eosinophil-associated histologic changes improved in all segments, epithelial changes persisted in the esophagus and stomach in patients with recurrent disease flares even after 1 year of treatment. Serum tryptase and GI mast cells were generally unchanged with treatment, and increases were not associated with disease flares. Serum levels of IL-4 and IL-5 increased with benralizumab treatment (both P < .05). Conclusions: Benralizumab treatment completely depleted blood and GI tissue eosinophilia in patients with eosinophilic GI disorders, but clinical response, while encouraging, was heterogeneous. Residual symptoms in some patients may reflect persistent epithelial changes in the upper GI tract.

Original languageEnglish (US)
JournalJournal of Allergy and Clinical Immunology: In Practice
DOIs
StateAccepted/In press - 2022

Keywords

  • Eosinophilia
  • Eosinophilic colitis
  • Eosinophilic enteritis
  • Eosinophilic esophagitis
  • Eosinophilic gastritis
  • Hypereosinophilic syndrome
  • mAb

ASJC Scopus subject areas

  • Immunology and Allergy

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