Arquivos de Asma, Alergia e Imunologia
https://www.aaai-asbai.org.br/article/doi/10.5935/2526-5393.20210058
Arquivos de Asma, Alergia e Imunologia
Artigo de Revisão

The role of biologics in eosinophilic esophagitis

O papel dos imunobiológicos na esofagite eosinofílica

Inara Patrícia Desidério; Igor Garcia Sanches de-Souza; Guilherme Gonçalves Ferrigolli; Marcelo Vivolo Aun; Renata Rodrigues Cocco

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Abstract

Eosinophilic esophagitis (EoE) is a chronic inflammation in the esophageal mucosa driven by an antigen-mediated abnormal immune response with apparent increasing prevalence worldwide. Genetically predisposed individuals present with a dysfunctional esophageal barrier and an abnormal immune response mediated by Th2 and IgE against certain allergens. Consequently, esophageal lesions can cause dysmotility, fibrosis and loss of esophageal barrier function. Clinical manifestations are age-related and include symptoms of esophageal dysfunction. Diagnosis is established by specific histological features associated with the presence of at least 15 eosinophils per high-power field. Management of EoE includes control of allergic diseases with diet restrictions and/or pharmacological treatment with proton-pump inhibitors and corticosteroids, not completely effective and limited by possible side effects and impairment of quality of life. Although immunological mechanisms of EoE are still less clear than other allergic diseases, biologic trials indicate some promising perspectives for EoE management. The purpose of this review is to present the current evidence of biologic drugs as options for EoE treatment.

Keywords

Biological products, diagnosis, endoscopy.

Resumo

Esofagite eosinofílica (EOE) é uma inflamação crônica da mucosa esofágica com resposta imune antígeno-mediada anormal e com aparente aumento mundial na prevalência. Indivíduos geneticamente predispostos se apresentam com quadro de disfunção da barreira esofágica e uma resposta imune, mediada por TH2 e IGE, anormal contra certos alérgenos. Consequentemente, lesões esofágicas podem causar dismotilidade, fibrose e perda da função de barreira. O quadro clínico apresenta variação conforme idade e inclui sintomas de disfunção esofágica. O diagnóstico é estabelecido por achados histológicos específicos associados à presença de, ao menos, 15 eosinófilos por campo de alta potência. O manejo inclui controle do quadro alérgico com restrição dietética e/ou tratamento medicamentoso com bloqueadores da bomba de prótons e corticosteroides. São tratamentos sem completa efetividade, com efeitos colaterais e prejuízo na qualidade de vida. Ainda que os mecanismos imunológicos da EOE sejam menos claros que as demais doenças alérgicas, novos ensaios com imunobiológicos salientam uma perspectiva promissora de tratamento para a EOE. O objetivo desta revisão é apresentar as atuais evidências de uso de imunobiológicos como uma nova opção de terapêutica para a esofagite eosinofílica.

Palavras-chave

Produtos biológicos, diagnóstico, endoscopia.

Referências

1. Furuta GT, Katzka DA. Eosinophilic Esophagitis. N Engl J Med. 2015;373(17):1640-8.

2. Moawad FJ. Eosinophilic Esophagitis: Incidence and Prevalence. Gastrointest Endosc Clin N Am. 2018;28(1):15-25.

3. Atkins D, Furuta GT, Liacouras CA, Spergel JM. Eosinophilic esophagitis phenotypes: Ready for prime time? Pediatr Allergy Immunol. 2017;28(4):312-9.

4. Vinit C, Dieme A, Courbage S, Dehaine C, Dufeu CM, Jacquemot S, et al. Eosinophilic esophagitis: Pathophysiology, diagnosis, and management. Arch Pediatr. 2019;26(3):182-90.

5. Shaheen NJ, Mukkada V, Eichinger CS, Schofield H, Todorova L, Falk GW. Natural history of eosinophilic esophagitis: a systematic review of epidemiology and disease course. Dis Esophagus. 2018;31(8):doy015.

6. Greuter T, Hirano I, Dellon ES. Emerging therapies for eosinophilic esophagitis. J Allergy Clin Immunol. 2020;145(1):38-45.

7. O'Shea KM, Aceves SS, Dellon ES, Gupta SK, Spergel JM, Furuta GT, et al. Pathophysiology of Eosinophilic Esophagitis.Gastroenterology. 2018;154(2):333-45.

8. Travers J, Rochman M, Miracle CE, Cohen JP, Rothenberg ME. Linking impaired skin barrier function to esophageal allergic inflammation via IL-33. J Allergy Clin Immunol. 2016;138:1381-3.

9. Ryu S, Lee KH, Tizaoui K, Terrazzino S, Cargnin S, Effenberger M, et al. Pathogenesis of Eosinophilic Esophagitis: A Comprehensive Review of the Genetic and Molecular Aspects. Int J Mol Sci. 2020;21(19):7253.

10. Zuo L, Fulkerson PC, Finkelman FD, Mingler M, Fischetti CA, Blanchard C, et al. IL-13 induces esophageal remodeling and gene expression by an eosinophil-independent, IL-13R alpha 2-inhibited pathway. J Immunol. 2010;185(1):660-9.

11. Forbes EE, Groschwitz K, Abonia JP, Brandt EB, Cohen E, Blanchard C, et al. IL- 9 and mast cell-mediated intestinal permeability predisposes to oral antigen hypersensitivity. J Exp Med 2008;205:897-913.

12. Zhu X, Wang M, Mavi P, Rayapudi M, Pandey AK, Kaul A, et al. Interleukin-15 expression is increased in human eosinophilic esophagitis and mediates pathogenesis in mice. Gastroenterology 2010;139:182-93.e7.

13. Lim AH, Wong S, Nguyen NQ. Eosinophilic Esophagitis and IgG4: Is There a Relationship? Dig Dis Sci. 2021 Feb 3. doi: 10.1007/ s10620-020-06788-0. Epub ahead of print. PMID: 33534011.

14. Gonsalves NP, Aceves SS. Diagnosis and treatment of eosinophilic esophagitis. J Allergy Clin Immunol. 2020;145(1):1-7.

15. Ballmer-Weber BK. Value of allergy tests for the diagnosis of food allergy. Dig Dis. 2014;32(1-2):84-8.

16. Eckmann JD, Ravi K, Katzka DA, Davis DR, See JA, Geno DR, et al. Efficacy of Atopy Patch Testing in Directed Dietary Therapy of Eosinophilic Esophagitis: A Pilot Study. Dig Dis Sci. 2018;63(3):694‑‑702.

17. Lucendo AJ, Arias A, Gonzalez-Cervera J, Yague-Compadre JL, Guagnozzi D, Angueira T, et al. Empiric 6-food elimination diet induced and maintained prolonged remission in patients with adult eosinophilic esophagitis: a prospective study on the food cause of the disease. J Allergy Clin Immunol. 2013;131:797-804.

18. Molina-Infante J, Arias A, Barrio J, Rodriguez-Sanchez J, SanchezCazalilla M, Lucendo AJ. Four-food group elimination diet for adult eosinophilic esophagitis: a prospective multicenter study. J Allergy Clin Immunol. 2014;134:1093-9.

19. Murali AR, Gupta A, Attar BM, Ravi V, Koduru P. Topical steroids in eosinophilic esophagitis: Systematic review and meta-analysis of placebo-controlled randomized clinical trials. J Gastroenterol Hepatol. 2016;31:1111-9.

20. Dellon ES, Liacouras CA, Molina-Infante J, Furuta GT, Spergel JM, Zevit N, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: proceedings of the AGREE conference. Gastroenterology. 2018;155:1022-33.

21. Agache I, Rocha C, Beltran J, Song Y, Posso M, Solà I, et al. Efficacy and safety of treatment with biologicals (benralizumab, dupilumab and omalizumab) for severe allergic asthma: A systematic review for the EAACI Guidelines - recommendations on the use of biologicals in severe asthma. Allergy. 2020 ;75(5):1043-57.

22. Seegräber M, Srour J, Walter A, Knop M, Wollenberg A. Dupilumab for treatment of atopic dermatitis. Expert Rev Clin Pharmacol. 2018;11(5):467-74.

23. Sastre J, Dávila I. Dupilumab: A New Paradigm for the Treatment of Allergic Diseases. J Investig Allergol Clin Immunol. 2018;28(3):139‑50.

24. Thomson NC, Chaudhuri R. Omalizumab: clinical use for the management of asthma. Clin Med Insights Circ Respir Pulm Med. 2012;6:27-40.

25. Maurer M, Rosén K, Hsieh HJ, Saini S, Grattan C, Arnau AG, et al. Omalizumab for the Treatment of Chronic Idiopathic or Spontaneous Urticaria. N Engl J Med. 2013;368:924-35.

26. Rocha R, Vitor AB, Trindade E, Lima R, Tavares M, Lopes J, et al. Omalizumab in the treatment of eosinophilic esophagitis and food allergy. Eur J Pediatr. 2011;170(11):1471-4.

27. Arasi S, Costa S, Magazzù G, Ieni A, Crisafulli G, Caminiti L, et al. Omalizumab therapy in a 13-year-old boy with severe persistent asthma and concomitant eosinophilic esophagitis. Ital J Pediatr. 2016;42:32.

28. Loizou D, Enav B, Komlodi-Pasztor E, Hider P, Kim-Chang J, Noonan L, et al. A pilot study of omalizumab in eosinophilic esophagitis. PLoS One. 2015;10: e0113483.

29. Clayton F, Fang JC, Gleich GJ, Lucendo AJ, Olalla JM, Vinson LA, et al. Eosinophilic esophagitis in adults is associated with IgG4 and not mediated by IgE. Gastroenterology. 2014;147(3):602-9.

30. Hom S, Pisano M. Reslizumab (Cinqair): An Interleukin-5 Antagonist for Severe Asthma of the Eosinophilic Phenotype. Pharmacology & Therapeutics. 2017;42(9):564-8.

31. Markowitz JE, Jobe L, Miller M, Frost C, Laney Z, Eke R. Safety and Efficacy of Reslizumab for Children and Adolescents With Eosinophilic Esophagitis Treated for 9 Years. J Pediatr Gastroenterol Nutr. 2018;66(6):893-7.

32. Spergel JM, Rothenberg ME, Collins MH, Furuta GT, Markowitz JE, Fuchs G 3rd, et al. Reslizumab in children and adolescents with eosinophilic esophagitis: results of a double-blind, randomized, placebo-controlled trial. J Allergy Clin Immunol. 2012;129(2):456- 63,463.e1-3.

33. Assa'ad AH, Gupta SK, Collins MH, Thomson M, Heath AT, Smith DA, et al. An antibody against IL-5 reduces numbers of esophageal intraepithelial eosinophils in children with eosinophilic esophagitis. Gastroenterology. 2011;141(5):1593-604.

34. Straumann A, Conus S, Grzonka P, Kita H, Kephart G, Bussmann C, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010;59(1):21-30.

35. Conus S, Straumann A, Bettler E, Simon HU. Mepolizumab does not alter levels of eosinophils, T cells, and mast cells in the duodenal mucosa in eosinophilic esophagitis. J Allergy Clin Immunol. 2010;126(1):175-7.

36. ClinicalTrias.gov. A study of Benralizumab in patients with Eosinophilic Esophagitis (MESSINA) [Internet]. Available in: https://clinicaltrials.gov/ct2/show/NCT04543409?term=Benralizumab&cond=Eosinophilic+Esophagitis&draw=2&rank=1. Accessed on: 10/17/2020.

37. Weidinger S, Novak N. Atopic dermatitis. Lancet. 2016;387:1109‑22.

38. ClinicalTrias.gov. Study to determine the efficacy and safety of Dupilumab in adult and adolescent patients with Eosinophilic Esophagitis (EoE) [Internet]. Available in: https://clinicaltrials.gov/ct2/show/NCT03633617?type=Intr&cond=Esophagitis%2C+Eosinophilic&draw=4. Accessed on: 10/17/2020.

39. ClinicalTrias.gov. Study to investigate the efficacy and safety of Dupilumab in pediatric patients with active Eosinophilic Esophagitis (EoE) (EoE KIDS) [Internet]. Available in: https://clinicaltrials.gov/ct2/show/NCT04394351?type=Intr&cond=Esophagitis%2C+Eosinophilic&draw=3. Accessed on: 10/17/2020.

40. Hirano I, Dellon ES, Hamilton JD, Collins MH, Peterson K, Chehade M, et al. Efficacy of Dupilumab in a Phase 2 Randomized Trial of Adults With Active Eosinophilic Esophagitis. Gastroenterology. 2020 Jan;158(1):111-122.e10. doi: 10.1053/j.gastro.2019.09.042. Epub 2019 Oct 5.

41. Judd LM, Heine RG, Menheniott TR, Buzzelli J, O'Brien-Simpson N, Pavlic D, et al. Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice. Am J Physiol Gastrointest Liver Physiol. 2016;310(1):G13-25.

42. ClinicalTrias.gov. A study of Lirentelimab (AK002) in patients with active Eosinophilic Esophagitis (KRYPTOS) [Internet]. Available in: https://clinicaltrials.gov/ct2/show/NCT04322708?type=Intr&cond=Esophagitis%2C+Eosinophilic&draw=4. Accessed on: 10/17/2020.

43. ClinicalTrias.gov. Efficacy and safety of QAX576 in patients with Eosinophilic Esophagitis [Internet]. Available in: https://clinicaltrials.gov/ct2/show/NCT01022970?type=Intr&cond=Esophagitis%2C+Eosinophilic&draw=4. Accessed on: 10/17/2020.

44. ClinicalTrias.gov. Dose ranging study of RPC4046 in Eosinophilic Esophagitis [Internet]. Available in: https://clinicaltrials.gov/ct2/show/NCT02098473?type=Intr&cond=Esophagitis%2C+Eosinophilic&draw=5. Accessed on: 10/17/2020.

45. Gann PH, Deaton RJ, McMahon N, Collins MH, Dellon ES, Hirano I, et al. An anti-IL-13 antibody reverses epithelial-mesenchymal transition biomarkers in eosinophilic esophagitis: Phase 2 trial results. J Allergy Clin Immunol. 2020;146(2):367-76. No conflicts of interest declared concerning the publication of this article.

46. ClinicalTrias.gov. Off label use of Infliximab in adult patients with severe Eosinophilic Esophagitis (IEE) [Internet]. Available in: https://clinicaltrials.gov/ct2/show/NCT00523354?type=Intr&cond=Esophagitis%2C+Eosinophilic&draw=3. Accessed on: 09/19/20210.

47. Ko E, Chehade M. Biological Therapies for Eosinophilic Esophagitis: Where Do We Stand? Clin Rev Allergy Immunol. 2018;55(2):205‑16.


Submetido em:
24/07/2021

Aceito em:
12/10/2021

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