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Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?

Clinical Reviews in Allergy & Immunology volume 55, pages 205–216 (2018)Cite this article

Abstract

Eosinophilic esophagitis (EoE) is an immune-mediated, chronic esophageal disease characterized by esophageal symptoms and esophageal eosinophilia. It is triggered by foods and possibly by environmental allergens. Currently, there are no FDA-approved therapies for EoE. Commonly used treatments include dietary restrictions and topical corticosteroids. Many of these therapies are suboptimal in their efficacy, have side effects, or diminish patients’ quality of life. Biologic therapies for EoE have therefore been sought as an alternative. The mechanism by which food allergens trigger EoE is thought to be a T helper type 2 (Th2) reaction, resulting in secretion of the cytokines IL-4, IL-5, and IL-13. IL-5 induces eosinophil production and trafficking to the esophagus, and IL-13 induces esophageal epithelial cells to secrete eotaxin-3, which drives eosinophil chemotaxis and activation. Mepolizumab and reslizumab, two anti-IL-5 antibodies, were studied in children and adults with EoE and resulted in reduction of esophageal tissue and blood eosinophils, but no significant reduction in symptoms. QAX576, an anti-IL-13 antibody, was studied in adults with EoE and showed a decrease in the esophageal eosinophil load and a trend towards clinical improvement. Since in situ IgE production was demonstrated in the EoE esophagus, omalizumab, an anti-IgE antibody, was studied in patients with EoE and not found to be overall beneficial. Furthermore, given the increased esophageal epithelial cell TNF-α expression in EoE, infliximab, an anti-TNF-α antibody, was studied in patients with EoE, with lack of success both clinically and histologically. In summary, although none of the biologicals studied so far in EoE have been highly effective, many demonstrated some histological benefit, especially those that targeted the Th2 axis. Therefore, the future for biologicals is promising as the pathophysiology of EoE is better understood, clinical assessment tools are validated, identification of patient subsets that respond best to biologicals is made, and dosages of biologicals are optimized.

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Fig. 1

Abbreviations

CCR3:

Chemokine receptor type 3

EoE:

Eosinophilic esophagitis

HPF:

High power field

IgE:

Immunoglobulin E

IL:

Interleukin

MDQ:

Mayo dysphagia questionnaire

PPI:

Proton pump inhibitor

Th2:

T helper type 2

TNF-α:

tumor necrosis factor-α

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Affiliations

  1. Mount Sinai Center for Eosinophilic Disorders, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1198, New York, NY, 10029, USA

    Emily Ko & Mirna Chehade

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  1. Emily Ko
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  2. Mirna Chehade
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Correspondence to Mirna Chehade.

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Conflicts of Interest

Emily Ko has nothing to disclose. Mirna Chehade has the following to disclose: received funding for research from Regeneron, Shire and Nutricia. Received consulting fees from Actelion, Shire and Allakos.

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This articles does not contain any studies with human participants or animals performed by any of the authors.

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Ko, E., Chehade, M. Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand?. Clinic Rev Allerg Immunol 55, 205–216 (2018). https://doi.org/10.1007/s12016-018-8674-3

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  • DOI: https://doi.org/10.1007/s12016-018-8674-3

Keywords

  • Eosinophilic esophagitis
  • Biologic
  • Mepolizumab
  • Reslizumab
  • Omalizumab
  • Infliximab
  • QAX576
  • T helper type 2 immunity
  • IL-13
  • IL-15
  • IgE
  • TNF-α