Skip to main content

Eosinophilic Esophagitis: the Potential Role of Biologics in its Treatment

Clinical Reviews in Allergy & Immunology volume 59, pages 150–159 (2020)Cite this article

Abstract

Eosinophilic esophagitis (EoE) is a chronic, relapsing inflammatory disease of the esophagus, characterized by the presence of significant esophageal mucosal eosinophilic infiltrates. The clinical presentation of EoE in childhood may include failure to thrive and feeding intolerance. The complication of food impaction is often related to the presence of strictures or narrow caliber esophagus. Over the last decade, there has been tremendous progress in the field of eosinophilic disorders, particularly eosinophilic esophagitis. Conventional treatment of eosinophilic esophagitis involves topical swallowed steroids, systemic steroids, elimination diets, and/or esophageal dilation. However, treatment outcomes with the above modalities are not satisfactory for all patients with EoE and alternative treatments are clearly needed. There has been ongoing research targeting the treatment-refractory population of patients with EoE and the population with long-term consequences of the disease and its treatment. With the significant eosinophilic infiltration that characterizes EoE, anti-IL-5 therapies designed to target eosinophilic inflammation have been some of the most studied anti-inflammatory biologic therapies in EoE. In the studies published to date, while various IL-5 inhibitors have decreased the numbers of esophageal eosinophils, they have not depleted them to the levels consistent with histologic remission of EoE. As additional biologics that modulate Th2-mediated immunity are trialed for the treatment of EoE, we stand to learn more about the inflammatory factors mediating this challenging condition. In this review, we discuss the alternative modes of therapy in EoE that have emerged, with a focus on anti-IL-5 therapies and other biologics, their variation of success, and ultimately, the future of treatment in this field.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

Fig. 1
Fig. 2

References

  1. Cianferoni A, Spergel JM (2014) Immunotherapeutic approaches for the treatment of eosinophilic esophagitis. Immunotherapy 6(3):321–331

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. Furuta GT, Liacouras CA, Collins MH, Gupta SK, Justinich C, Putnam PE, Bonis P, Hassall E, Straumann A, Rothenberg ME, First International Gastrointestinal Eosinophil Research Symposium (FIGERS) Subcommittees (2007) Eosinophilic esophagitis in children and adults: a systematic review and consensus recommendations for diagnosis and treatment. Gastroenterology 133(4):1342–1363

    CAS  PubMed  Article  Google Scholar 

  3. Saffari H et al (2012) Patchy eosinophil distributions in an esophagectomy specimen from a patient with eosinophilic esophagitis: implications for endoscopic biopsy. J Allergy Clin Immunol 130(3):798–800

    PubMed  PubMed Central  Article  Google Scholar 

  4. Collins MH (2014) Histopathology of eosinophilic esophagitis. Dig Dis 32(1–2):68–73

    PubMed  Article  Google Scholar 

  5. Dellon ES et al (2013) ACG clinical guideline: evidenced based approach to the diagnosis and management of esophageal eosinophilia and eosinophilic esophagitis (EoE). Am J Gastroenterol 108(5):679–692 quiz 693

    PubMed  Article  Google Scholar 

  6. D'Alessandro A, Esposito D, Pesce M, Cuomo R, de Palma GD, Sarnelli G (2015) Eosinophilic esophagitis: from pathophysiology to treatment. World J Gastrointest Pathophysiol 6(4):150–158

    PubMed  PubMed Central  Article  Google Scholar 

  7. Blanchard C, Stucke EM, Rodriguez-Jimenez B, Burwinkel K, Collins MH, Ahrens A, Alexander ES, Butz BK, Jameson SC, Kaul A, Franciosi JP, Kushner JP, Putnam PE, Abonia JP, Rothenberg ME (2011) A striking local esophageal cytokine expression profile in eosinophilic esophagitis. J Allergy Clin Immunol 127(1):208–217 217 e1-7

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  8. Raheem M et al (2014) The pathophysiology of eosinophilic esophagitis. Front Pediatr 2:41

    PubMed  PubMed Central  Article  Google Scholar 

  9. Loizou D et al (2015) A pilot study of omalizumab in eosinophilic esophagitis. PLoS One 10(3):e0113483

    PubMed  PubMed Central  Article  Google Scholar 

  10. Mishra A et al (2008) Esophageal remodeling develops as a consequence of tissue specific IL-5-induced eosinophilia. Gastroenterology 134(1):204–214

    PubMed  Article  Google Scholar 

  11. Mavi P et al (2012) Esophageal functional impairments in experimental eosinophilic esophagitis. Am J Physiol Gastrointest Liver Physiol 302(11):G1347–G1355

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. Legrand F, Klion AD (2015) Biologic therapies targeting eosinophils: current status and future prospects. J Allergy Clin Immunol Pract 3(2):167–174

    PubMed  PubMed Central  Article  Google Scholar 

  13. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G III, O’Gorman MA, Abonia JP, Young J, Henkel T, Wilkins HJ, Liacouras CA (2012) Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol 129(2):456–463 463 e1-3

    CAS  PubMed  Article  Google Scholar 

  14. Markowitz JE et al (2016) Long-term safety and efficacy of reslizumab in children and adolescents with eosinophilic esophagitis: a review of 477 doses in 12 children over 7 years. J Allergy Clin Immunol 137(2):AB234

    Article  Google Scholar 

  15. Identifier NCT00635089. Open-label extension study of reslizumab in pediatric subjects with eosinophilic esophagitis. National Library of Medicine: ClinicalTrials.gov.

  16. Rothenberg ME, Klion AD, Roufosse FE, Kahn JE, Weller PF, Simon HU, Schwartz LB, Rosenwasser LJ, Ring J, Griffin EF, Haig AE, Frewer PI, Parkin JM, Gleich GJ, Mepolizumab HES Study Group (2008) Treatment of patients with the hypereosinophilic syndrome with mepolizumab. N Engl J Med 358(12):1215–1228

    CAS  PubMed  Article  Google Scholar 

  17. Stein ML, Collins MH, Villanueva JM, Kushner JP, Putnam PE, Buckmeier BK, Filipovich AH, Assa’ad AH, Rothenberg ME (2006) Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol 118(6):1312–1319

    CAS  PubMed  Article  Google Scholar 

  18. Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, Beglinger C, Smith DA, Patel J, Byrne M, Simon HU (2010) Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut 59(1):21–30

    CAS  PubMed  Article  Google Scholar 

  19. Assa'ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, Perschy TL, Jurgensen CH, Ortega HG, Aceves SS (2011) An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology 141(5):1593–1604

    CAS  PubMed  Article  Google Scholar 

  20. Goyal A, Cheng E (2016) Recent discoveries and emerging therapeutics in eosinophilic esophagitis. World J Gastrointest Pharmacol Ther 7(1):21–32

    PubMed  PubMed Central  Article  Google Scholar 

  21. Clayton F, Fang JC, Gleich GJ, Lucendo AJ, Olalla JM, Vinson LA, Lowichik A, Chen X, Emerson L, Cox K, O'Gorman MA, Peterson KA (2014) Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology 147(3):602–609

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. Rocha R et al (2011) Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Eur J Pediatr 170(11):1471–1474

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. Taille C et al (2013) Monoclonal anti-TNF-alpha antibodies for severe steroid-dependent asthma: a case series. Open Respir Med J 7(7):21–25

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  24. Berry MA, Hargadon B, Shelley M, Parker D, Shaw DE, Green RH, Bradding P, Brightling CE, Wardlaw AJ, Pavord ID (2006) Evidence of a role of tumor necrosis factor alpha in refractory asthma. N Engl J Med 354(7):697–708

    CAS  PubMed  Article  Google Scholar 

  25. Straumann A, Bussmann C, Conus S, Beglinger C, Simon HU (2008) Anti-TNF-alpha (infliximab) therapy for severe adult eosinophilic esophagitis. J Allergy Clin Immunol 122(2):425–427

    CAS  PubMed  Article  Google Scholar 

  26. Straumann A, Hoesli S, Bussmann C, Stuck M, Perkins M, Collins LP, Payton M, Pettipher R, Hunter M, Steiner J, Simon HU (2013) Anti-eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis. Allergy 68(3):375–385

    CAS  PubMed  Article  Google Scholar 

  27. Blanchard C, Mishra A, Saito-Akei H, Monk P, Anderson I, Rothenberg ME (2005) Inhibition of human interleukin-13-induced respiratory and oesophageal inflammation by anti-human-interleukin-13 antibody (CAT-354). Clin Exp Allergy 35(8):1096–1103

    CAS  PubMed  Article  Google Scholar 

  28. Rothenberg ME, Wen T, Greenberg A, Alpan O, Enav B, Hirano I, Nadeau K, Kaiser S, Peters T, Perez A, Jones I, Arm JP, Strieter RM, Sabo R, Gunawardena KA (2015) Intravenous anti-IL-13 mAb QAX576 for the treatment of eosinophilic esophagitis. J Allergy Clin Immunol 135(2):500–507

    CAS  PubMed  Article  Google Scholar 

  29. Hirano I et al (2018) RPC4046, a monoclonal antibody against IL13, reduces histologic and endoscopic activity in patients with eosinophilic esophagitis. Gastroenterology

  30. Hirano I et al (2017) Dupilumab efficacy and safety in adult patients with active eosinophilic esophagitis: a randomized, double blind, placebo controlled phase 2 trial. World Congress of Gastroenterology at ACG, Orlando

    Google Scholar 

  31. Identifier NCT03633617. Study to determine the efficacy and safety of dupilumab in adult and adolescent patients with eosinophilic esophagitis (EoE). National Library of Medicine: ClinicalTrials.gov.

  32. Straumann A (2014) Eosinophilic esophagitis: emerging therapies and future perspectives. Gastroenterol Clin N Am 43(2):385–394

    Article  Google Scholar 

  33. Identifier NCT03656380. Mepo for EoE study. National Library of Medicine: ClinicalTrials.gov.

Download references

Author information

Affiliations

  1. Division of Gastroenterology, Department of Pediatrics, Loma Linda University Children’s Hospital, 11234 Anderson St., Loma Linda, CA, 92354, USA

    Shelly Choudhury

  2. Division of Gastroenterology, Department of Pediatrics, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

    Susan Baker

Authors
  1. Shelly Choudhury
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Susan Baker
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shelly Choudhury.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

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

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Choudhury, S., Baker, S. Eosinophilic Esophagitis: the Potential Role of Biologics in its Treatment. Clinic Rev Allerg Immunol 59, 150–159 (2020). https://doi.org/10.1007/s12016-019-08749-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12016-019-08749-6

Keywords

  • Eosinophilic esophagitis
  • Eosinophils
  • Anti-IL-5
  • Anti-IgE
  • Anti IL-13
  • Anti-CRTH
  • Anti-TNF-alpha