Manejo dos eventos adversos do dupilumabe
na dermatite atópica e no prurigo nodular

Mara Giavina-Bianchi

doi:10.5935/2526-5393.20230071

Artigo de Revisão

Manejo dos eventos adversos do dupilumabe na dermatite atópica e no prurigo nodular

Management of the adverse effects of dupilumab in atopic dermatitis and prurigo nodularis

Mara Giavina-Bianchi

http://dx.doi.org/10.5935/2526-5393.20230071 Arq Asma Alerg Imunol, vol.8, n1, p.14-20, 2024

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Resumo

A dermatite atópica (DA) e o prurigo nodular (PN) são doenças inflamatórias da pele que cursam com lesões variadas, como eczemas, pápulas e nódulos, acompanhados de intenso prurido e, nos casos graves, de importante prejuízo da qualidade de vida para os pacientes e seus familiares. O dupilumabe está aprovado no Brasil para o manejo das duas condições: DA moderada/ grave e PN que não responde aos tratamentos tópicos. A eficácia e segurança do dupilumabe foram amplamente estabelecidas para ambas as condições em ensaios clínicos e estudos de vida real. Este artigo tem como objetivo revisar os principais eventos adversos (EAD) associados ao uso do dupilumabe em DA e PN, e auxiliar no seu manejo. Desde o início do uso da medicação, há alguns anos, os principais EAD reportados foram: a reação no local da injeção, a doença da superfície ocular (conjuntivite não infecciosa, blefarite, olhos secos), a eosinofilia e o eritema de face/ pescoço. Outras manifestações também foram observadas em pacientes com DA em uso de dupilumabe, mas sem associação comprovada: psoríase, artralgia e alopecia areata. Apesar de muito infrequentemente levarem à suspensão do dupilumabe, é fundamental que os médicos prescritores deste medicamento para estas condições, dermatologistas e imunoalergistas, saibam detectar e manejar seus possíveis eventos adversos.

Palavras-chave

Dermatite atópica, prurigo nodular, dupilumabe, eventos adversos, manejo.

Abstract

Atopic dermatitis (AD) and prurigo nodularis (PN) are inflammatory skin diseases characterized by various lesions such as eczema, papules, and nodules, with marked pruritus and, in severe cases, significant impairment of quality of life for patients and their families. Dupilumab is approved in Brazil for the management of both moderate/severe AD and PN that does not respond to topical treatments. The efficacy and safety of dupilumab have been extensively established for both conditions in clinical trials and real-world studies. This article aims to review the main adverse events (AEs) associated with the use of dupilumab in AD and PN and assist in their management. Since the introduction of dupilumab a few years ago, the main reported AEs have been injection site reactions, ocular surface disease (non-infectious conjunctivitis, blepharitis, dry eyes), eosinophilia, and facial/ neck erythema. Other manifestations have also been observed in patients with AD on dupilumab, but without proven association: psoriasis, arthralgia, and alopecia areata. Although AEs very infrequently lead to discontinuation of dupilumab, it is crucial that physicians prescribing it for these conditions, dermatologists, and immunologists know how to detect and manage its possible adverse effects.

Keywords

Atopic dermatitis, prurigo nodularis, dupilumab, drugrelated side effects and adverse reactions, management.

Referências

1. Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II. J Eur Acad Dermatol Venereol. 2018;32(6):850-78.

2. Wollenberg A, Barbarot S, Bieber T, Christen-Zaech S, Deleuran M, Fink-Wagner A, et al. Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I. J Eur Acad Dermatol Venereol. 2018;32(5):657-82.

3. Kay J, Gawkrodger DJ, Mortimer MJ, Jaron AG. The prevalence of childhood atopic eczema in a general population. J Am Acad Dermatol. 1994;30(1):35-9.

4. Silverberg JI, Hanifin JM. Adult eczema prevalence and associations with asthma and other health and demographic factors: a US population-based study. J Allergy Clin Immunol. 2013;132(5):1132-8.

5. Giavina Bianchi M, Santos AP, Cordioli E. The majority of skin lesions in pediatric primary care attention could be managed by Teledermatology. PLoS One. 2019;14(12):e0225479.

6. Silverberg JI, Gelfand JM, Margolis DJ, Boguniewicz M, Fonacier L, Grayson MH, et al. Symptoms and diagnosis of anxiety and depression in atopic dermatitis in U.S. adults. Br J Dermatol. 2019;181(3):554-65.

7. Campos ALB, Araújo FM, Santos MALD, Santos AASD, Pires CAA. Impact of atopic dermatitis on the quality of life of pediatric patients and their guardians. Rev Paul Pediatr. 2017;35(1):5-10.

8. Cao P, Xu W, Jiang S, Zhang L. Dupilumab for the treatment of prurigo nodularis: A systematic review. Front Immunol. 2023;14:1092685.

9. Wollenberg A, Beck LA, Blauvelt A, Simpson EL, Chen Z, Chen Q, et al. Laboratory safety of dupilumab in moderate-to-severe atopic dermatitis: results from three phase III trials (LIBERTY AD SOLO 1, LIBERTY AD SOLO 2, LIBERTY AD CHRONOS). Br J Dermatol. 2020;182(5):1120-35.

10. Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med. 2016;375(24):2335-48.

11. Stingeni L, Bianchi L, Antonelli E, Caroppo ES, Ferrucci SM, Ortoncelli M, et al. Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience. J Eur Acad Dermatol Venereol. 2022;36(8):1292-9.

12. Faiz S, Giovannelli J, Podevin C, Jachiet M, Bouaziz JD, Reguiai Z, et al. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort. J Am Acad Dermatol. 2019;81(1):143-51.

13. Sanofi. Press Release: Dupixent® (dupilumab) approved by FDA as the first and only treatment indicated for prurigo nodularis [Internet]. Disponível em: https://www.sanofi.com/en/media-room/press-releases/2022/2022-09-28-22-05-26-2524764.

14. Brasil, Ministério da Saúde, Agência Nacional de Vigilância Sanitária (Anvisa). DUPIXENT (dupilumabe): nova indicação [Internet]. 2023. Disponível em: https://www.gov.br/anvisa/pt-br/assuntos/medicamentos/novos-medicamentos-e-indicacoes/dupixentdupilumabe-nova-indicacao-3#:~:text =)%3A%20nova%20 indica%C3%A7%C3%A3o-,DUPIXENT%20(dupilumabe)%3A%20nova%20indica%C3%A7%C3%A3o,estes%20tratamentos%20 n%C3%A3o%20s%C3%A3o%20aconselhados.

15. Yosipovitch G, Mollanazar N, Ständer S, Kwatra SG, Kim BS, Laws E, et al. Dupilumab in patients with prurigo nodularis: two randomized, double-blind, placebo-controlled phase 3 trials. Nat Med. 2023;29(5):1180-90.

16. Wenzel S, Ford L, Pearlman D, Spector S, Sher L, Skobieranda F, et al. Dupilumab in persistent asthma with elevated eosinophil levels. N Engl J Med. 2013;368(26):2455-66.

17. Guttman-Yassky E, Bissonnette R, Ungar B, Suárez-Fariñas M, Ardeleanu M, Esaki H, et al. Dupilumab progressively improves systemic and cutaneous abnormalities in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143(1):155-72.

18. Simpson EL, Paller AS, Siegfried EC, Boguniewicz M, Sher L, Gooderham MJ, et al. Efficacy and Safety of Dupilumab in Adolescents With Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2019.

19. Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, et al. Long-term management of moderate-tosevere atopic dermatitis with dupilumab and concomitant topical corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomised, double-blinded, placebo-controlled, phase 3 trial. Lancet. 2017;389(10086):2287-303.

20. Musters AH, van Lookeren FL, van der Gang LF, Middelkamp-Hup MA, Bosma AL, Jessurun NT, et al. Real-world reported adverse events related to systemic immunomodulating therapy in patients with atopic dermatitis: Results from the TREAT NL (TREatment of ATopic eczema, the Netherlands) registry. J Eur Acad Dermatol Venereol. 2023.

21. Kim PJ, Lansang RP, Vender R. A Systematic Review and Meta- Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections. J Cutan Med Surg. 2023;27(4):358-67.

22. Wu KK, Borba AJ, Deng PH, Armstrong AW. Association between atopic dermatitis and conjunctivitis in adults: a population-based study in the United States. J Dermatolog Treat. 2019:1-5.

23. Shokouhi Shoormasti R, Pourpak Z, Fazlollahi MR, Kazemnejad A, Nadali F, Ebadi Z, et al. The prevalence of allergic rhinitis, allergic conjunctivitis, atopic dermatitis and asthma among adults of Tehran. Iran J Public Health. 2018;47(11):1749-55.

24. Thyssen JP, Toft PB, Halling-Overgaard AS, Gislason GH, Skov L, Egeberg A. Incidence, prevalence, and risk of selected ocular disease in adults with atopic dermatitis. J Am Acad Dermatol. 2017;77(2):280-6.e1.

25. Schneider L, Hanifin J, Boguniewicz M, Eichenfield LF, Spergel JM, Dakovic R, et al. Study of the Atopic March: Development of Atopic Comorbidities. Pediatr Dermatol. 2016;33(4):388-98.

26. Henriksen L, Simonsen J, Haerskjold A, Linder M, Kieler H, Thomsen SF, et al. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. J Allergy Clin Immunol. 2015;136(2):360-6.e2.

27. Stensballe LG, Klansø L, Jensen A, Haerskjold A, Thomsen SF, Simonsen J. The validity of register data to identify children with atopic dermatitis, asthma or allergic rhinoconjunctivitis. Pediatr Allergy Immunol. 2017;28(6):535-42.

28. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Lancet. 1998;351(9111):1225-32.

29. Cronau H, Kankanala RR, Mauger T. Diagnosis and management of red eye in primary care. Am Fam Physician. 2010;81(2):137-44.

30. Yokoi K, Yokoi N, Kinoshita S. Impairment of ocular surface epithelium barrier function in patients with atopic dermatitis. Br J Ophthalmol. 1998;82(7):797-800.

31. Mantelli F, Mauris J, Argüeso P. The ocular surface epithelial barrier and other mechanisms of mucosal protection: from allergy to infectious diseases. Curr Opin Allergy Clin Immunol. 2013;13(5):563-8.

32. Akinlade B, Guttman-Yassky E, de Bruin-Weller M, Simpson EL, Blauvelt A, Cork MJ, et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019;181(3):459-73.

33. Ahn J, Lee DH, Na CH, Shim DH, Choi YS, Jung HJ, et al. Facial erythema in patients with atopic dermatitis treated with Dupilumab - a descriptive study of morphology and Aetiology. J Eur Acad Dermatol Venereol. 2022;36(11):2140-52.

34. Jo CE, Finstad A, Georgakopoulos JR, Piguet V, Yeung J, Drucker AM. Facial and neck erythema associated with dupilumab treatment: A systematic review. J Am Acad Dermatol. 2021;84(5):1339-47.

35. Napolitano M, Fabbrocini G, Patruno C. Dupilumab-associated cutaneous adverse events among adult patients with atopic dermatitis: A retrospective study. J Dermatol. 2023;50(7):880-7.

36. Li Y, Liu H, Zhang F. Biologics-Induced Immunophenotypic Cross- Switching in Patients with Psoriasis and Atopic Dermatitis. Indian J Dermatol. 2023;68(2):186-91.

37. Trave I, Salvi I, Burlando M, Cozzani E, Parodi A. "De Novo" Psoriasis and Relapse of Psoriasis Induced by Dupilumab: Three New Cases and Review of the Literature. J Clin Med. 2023;12(19):6291.

38. Schneeweiss MC, Wyss R, Schneeweiss S, Anand P, Jin Y, Dicesare E, et al. Joint pain in patients with atopic dermatitis receiving treatment with dupilumab: A US nationwide cohort study. J Am Acad Dermatol. 2024;90(1):134-7.

39. Yan X, Tayier M, Cheang ST, Liao Z, Dong Y, Yang Y, et al. Hair repigmentation and regrowth in a dupilumab-treated paediatric patient with alopecia areata and atopic dermatitis: a case report. Ther Adv Chronic Dis. 2023;14:20406223231191049.

40. Bur D, Kim K, Rogge M. Dupilumab Induced Hair Regrowth in Alopecia Totalis. J Drugs Dermatol. 2023;22(4):410-2.

41. Treister AD, Kraff-Cooper C, Lio PA. Risk Factors for Dupilumab- Associated Conjunctivitis in Patients With Atopic Dermatitis. JAMA Dermatol. 2018;154(10):1208-11.

42. Maudinet A, Law-Koune S, Duretz C, Lasek A, Modiano P, Tran THC. Ocular Surface Diseases Induced by Dupilumab in Severe Atopic Dermatitis. Ophthalmol Ther. 2019;8(3):485-90.

43. Ivert LU, Wahlgren CF, Ivert L, Lundqvist M, Bradley M. Eye Complications During Dupilumab Treatment for Severe Atopic Dermatitis. Acta Derm Venereol. 2019;99(4):375-8.

44. Barnes AC, Blandford AD, Perry JD. Cicatricial ectropion in a patient treated with dupilumab. Am J Ophthalmol Case Rep. 2017;7:120-2.

45. Levine RM, Tattersall IW, Gaudio PA, King BA. Cicatrizing Blepharoconjunctivitis Occurring During Dupilumab Treatment and a Proposed Algorithm for Its Management. JAMA Dermatol. 2018;154(12):1485-6.

46. Agnihotri G, Shi K, Lio PA. A Clinician's Guide to the Recognition and Management of Dupilumab-Associated Conjunctivitis. Drugs R D. 2019;19(4):311-8.

47. Guex-Crosier Y, Di-Lucca J, Häusermann P, Laffitte E, Saulite I, Schmid-Grendelmeier P, et al. Management of dupilumab-associated ocular surface diseases in atopic dermatitis patients. Swiss Med Wkly. 2021 Aug 20;151:w30020. doi: 10.4414/SMW.2021.w30020.

Submetido em:
30/03/2022

Aceito em:
12/11/2023