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Review
. 2018 Jul;142(1):24-31.e2.
doi: 10.1016/j.jaci.2018.05.018. Epub 2018 May 31.

Biological therapies for eosinophilic gastrointestinal diseases

Joshua B Wechsler  1 , Ikuo Hirano  2
Affiliations
Review

Biological therapies for eosinophilic gastrointestinal diseases

Joshua B Wechsler et al. J Allergy Clin Immunol. 2018 Jul.

Abstract

The scientific basis and the clinical application of mAb therapies that target specific immunologic pathways for eosinophilic gastrointestinal diseases are areas of active interest. There is a growing recognition of a subset of patients with eosinophilic esophagitis whose disease does not respond well to topical steroids or elimination diets. In addition, long-term use of corticosteroids presents possible risks that are currently being evaluated. Systemic therapy with a biologic agent offers potential advantages as a global approach that could limit the need for multiple, locally active medical therapies and allergen avoidance. The identification of novel biologic strategies is ongoing, and the recent validation of instruments and outcome measures to assess disease activity has proved essential in demonstrating efficacy. Studies using biologics that target IL-13 pathways in the treatment of eosinophilic esophagitis have demonstrated substantial promise.

Keywords: Eosinophilic esophagitis; dysphagia; esophageal strictures; esophagitis; food allergy; gastroesophageal reflux disease.

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Conflict of interest statement

Conflict of Interest Disclosure: Dr. Wechsler has nothing to disclose. Dr. Hirano reports consulting fees and research funding from Regeneron, Receptos, Shire, Adare, Allakos outside the submitted work.

Figures

Figure
Figure
Therapeutic targets for current and future biologics in eosinophilic esophagitis. Basophils and antigen-presenting cells mediate dietary antigen presentation to naïve T-cells (Th0), which through TSLP and IL-4 drives T-helper cell Type 2 (Th2) cell expansion. Th2 are recruited to the esophagus via integrins and prostaglandins and drive B-cell production of immunoglobulins, along with mast cell hyperplasia. Th2 cells secrete IL-5 which further enhances eosinophil recruitment via release of eotaxins and eosinophil survival. Th2 cells secrete IL-13, which dysregulates the epithelium to recruit Th2 inflammatory cells and promotes remodeling. Eosinophils and mast cells are effector cells that are activated to secrete proteases, cytokines and histamine which drive mucosal inflammatory changes and symptoms. TGF-β1 has a key role in fibrosis. Specific targets discussed include: 1) IL-5R, 2) Eotaxins, 3) IL4R/IL13, 4) CRTH2, 5) TSLP, 6) Siglec-8, 7) IgE, 8) TGF-β1, 9) Integrin α4β1/7
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