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Pharmacotherapies for the Treatment of Eosinophilic Esophagitis: State of the Art Review

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Abstract

Eosinophilic esophagitis (EoE), a chronic allergic disorder of the esophagus, is characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. The incidence of EoE has increased substantially over the past two decades, coinciding with the so-called allergy epidemic. Current treatment options consist of dietary intervention, endoscopic dilatation, and pharmacotherapy. Given that EoE is a chronic progressive disease that is prone to relapse after cessation of therapy, these treatment options are suboptimal for long-term management. Persistent, uncontrolled esophageal inflammation is associated with esophageal remodeling and stricture formation, thus, the creation and/or discovery of alternative treatments is of paramount importance. The pathogenesis of EoE is currently under intense investigation, and recent insights concerning cellular and molecular etiology have led to the development of therapies that target specific pathophysiological pathways. This article provides an overview of established EoE pharmacotherapies, which include proton pump inhibitors and swallowed topical steroids. Additionally, anti-allergic targets, immunosuppressives, and monoclonal antibodies (such as mepolizumab, reslizumab, QAX576, RPC4046, dupilumab, omalizumab, and infliximab) that have been evaluated as treatments for EoE are summarized. Finally, several promising therapeutic agents (e.g., sialic acid-binding immunoglobulin-like lectin 8 antibodies, the transforming growth factor-β1 signal blocker losartan, CC chemokine receptor type 3 antagonists, thymic stromal lymphopoietin antibodies, antibodies targeting the α4β7 integrin, anti-interleukin-9 antibodies, and anti-interleukin-15 antibodies) that target specific molecules or cells implicated in the pathogenesis of EoE are proposed.

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Authors and Affiliations

  1. Department of Gastroenterology and Hepatology, Academic Medical Centre, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

    Willemijn E. de Rooij & Albert J. Bredenoord

  2. Division of Gastroenterology and Hepatology, Center for Esophageal Diseases and Swallowing, University of North Carolina School of Medicine, Chapel Hill, NC, USA

    Evan S. Dellon

  3. Robarts Clinical Trials Inc, London, ON, Canada

    Claire E. Parker, Brian G. Feagan, Vipul Jairath & Christopher Ma

  4. Department of Medicine, University of Western Ontario, London, ON, Canada

    Brian G. Feagan & Vipul Jairath

  5. Department of Epidemiology and Biostatistics, University of Western Ontario, London, Canada

    Brian G. Feagan & Vipul Jairath

  6. Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada

    Christopher Ma

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  1. Willemijn E. de Rooij
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No sources of funding were used to conduct this study or prepare this manuscript.

Conflicts of interest

WEdR has no conflicts of interest that are directly relevant to the content of this article. ESD has received research funding from Adare, Allakos, GSK, Meritage, Miraca, Nutricia, Celgene/Receptos, Regeneron, and Shire; consulting fees from Adare, Alivio, Allakos, AstraZeneca, Banner, Calypso, Enumeral, EsoCap, Celgene/Receptos, GSK, Regeneron, Robarts and Shire; and educational grants from Allakos, Banner, and Holoclara. CEP is an employee of Robarts Clinical Trials Inc. BGF has received grant/research support from AbbVie Inc., Amgen Inc., AstraZeneca/MedImmune Ltd., Atlantic Pharmaceuticals Ltd., Boehringer-Ingelheim, Celgene Corporation, Celltech, Genentech Inc/Hoffmann-La Roche Ltd., Gilead Sciences Inc., GlaxoSmithKline (GSK), Janssen Research & Development LLC., Pfizer Inc., Receptos Inc./Celgene International, Sanofi, Santarus Inc., Takeda Development Center Americas Inc., Tillotts Pharma AG, and UCB; consulting fees from Abbott/AbbVie, Akebia Therapeutics, Allergan, Amgen, Applied Molecular Transport Inc., Aptevo Therapeutics, Astra Zeneca, Atlantic Pharma, Avir Pharma, Biogen Idec, BioMx Israel, Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech, Galapagos, GiCare Pharma, Gilead, Gossamer Pharma, GSK, Inception IBD Inc, JnJ/Janssen, Kyowa Kakko Kirin Co Ltd., Lexicon, Lilly, Lycera BioTech, Merck, Mesoblast Pharma, Millennium, Nestle, Nextbiotix, Novonordisk, Pfizer, Prometheus Therapeutics and Diagnostics, Progenity, Protagonist, Receptos, Salix Pharma, Shire, Sienna Biologics, Sigmoid Pharma, Sterna Biologicals, Synergy Pharma Inc., Takeda, Teva Pharma, TiGenix, Tillotts, UCB Pharma, Vertex Pharma, Vivelix Pharma, VHsquared Ltd., and Zyngenia; speakers bureaux fees from Abbott/AbbVie, JnJ/Janssen, Lilly, Takeda, Tillotts, and UCB Pharma; is a scientific advisory board member for Abbott/AbbVie, Allergan, Amgen, Astra Zeneca, Atlantic Pharma, Avaxia Biologics Inc., Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Centocor Inc., Elan/Biogen, Galapagos, Genentech/Roche, JnJ/Janssen, Merck, Nestle, Novartis, Novonordisk, Pfizer, Prometheus Laboratories, Protagonist, Salix Pharma, Sterna Biologicals, Takeda, Teva, TiGenix, Tillotts Pharma AG, and UCB Pharma; and is the Senior Scientific Officer of Robarts Clinical Trials Inc. CM has received consulting fees from Robarts Clinical Trials Inc. VJ has received consulting fees from AbbVie, Eli Lilly, GlaxoSmithKline, Arena Pharmaceuticals, Genetech, Pendopharm, Sandoz, Merck, Takeda, Janssen, Robarts Clinical Trials Inc, Topivert, and Celltrion; and speaker’s fees from Takeda, Janssen, Shire, Ferring, Abbvie, and Pfizer. AJB has received research funding from Nutricia, Norgine, and Bayer; and speaker and/or consulting fees from Laborie, EsoCap, Diversatek, Medtronic, DrFalk, Calypso, Thelial, Regeneron, Celgene, Bayer, Norgine, AstraZeneca, Almirall, and Allergan.

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de Rooij, W.E., Dellon, E.S., Parker, C.E. et al. Pharmacotherapies for the Treatment of Eosinophilic Esophagitis: State of the Art Review. Drugs 79, 1419–1434 (2019). https://doi.org/10.1007/s40265-019-01173-2

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