New treatment options for severe atopic dermatitis: upadacitinib. Review

Capa

Citar

Texto integral

Acesso aberto Acesso aberto
Acesso é fechado Acesso está concedido
Acesso é fechado Acesso é pago ou somente para assinantes

Resumo

Treatment of atopic dermatitis (AD) is based on the use of topical anti-inflammatory agents, and in cases of moderate and severe course – systemic drugs. The latter include glucocorticosteroids and classical immunosuppressants (cyclosporine A, methotrexate, azathioprine), which have many side effects and are poorly tolerated. Since 2017, the monoclonal antibody dupilumab (biological therapy) has been approved for the treatment of AD in adults and children (including those aged 6 months), and since 2021 – Janus kinase inhibitors (small molecules, or molecular therapy). Small molecule inhibitor research began over 50 years ago in the world’s leading pharmaceutical companies and was aimed at developing drugs that affect cytokine receptor signaling and regulation of the JAK/STAT response. This review describes the efficacy and safety of treating AD with upadacitinib, a selective, fast-acting JAK1 kinase inhibitor that significantly reduces itching and other clinical symptoms in patients with this difficult-to-treat disease as early as day 2 after administration. Upadacitinib is a systemic immunomodulator, the use of which will undoubtedly expand the available treatment options for moderate to severe AD in children and adults and, due to its modifying effect, represents an alternative to other systemic drugs.

Texto integral

Acesso é fechado

Sobre autores

Dali Macharadze

Gabrichevsky Moscow Research Institute of Epidemiology and Microbiology

Autor responsável pela correspondência
Email: nzayceva@bionika-media.ru
ORCID ID: 0000-0001-5999-7085

Dr. Sci. (Med.), Leading Researcher, Clinical Department

Rússia, Moscow

Bibliografia

  1. Darlenski R., Kozyrskyj A., Fluhr J., et al. Association between barrier impairment and skin microbiota in atopic dermatitis from a global perspective: Unmet needs and open questions. J Allergy Clin Immunol. 2021;148:1387–93. https://doi.org/10.1016/j.jaci.2021.10.002
  2. Izuhara K., Arima K., Yasunaga S. IL-4 and IL-13: their pathological roles in allergic diseases and their potential in developing new therapies. Curr Drug Targets Inflamm Allergy. 2002;3(1):263–9. https://doi.org/10.2174/1568010023344661
  3. Мачарадзе Д.Ш. Роль IL-4 и IL-13 в патогенезе атопического дерматита: пути ингибирования. Мед. иммунология. 2025;27(2):287–96. https://doi.org/10.15789/1563-0625-PRO-3070. [Macharadze D.Sh. Pathogenetic role of IL-4 and IL-13 in atopic dermatitis: The inhibitory pathways. Med Immunol. 2025;27(2):287–96 (In Russ.)]. https://doi.org/10.15789/1563-0625-PRO-3070
  4. Samra S., Bergerson J., Freeman A., Turvey S. JAK-STAT signaling pathway, immunodeficiency, inflammation, immune dysregulation, and inborn errors of immunity. J Allergy Clin Immunol. 2025;155(2):357–67. https://doi.org/10.1016/j.jaci.2024.09.020
  5. Linder C., Shourick J., Touhouche A., et al. Analysis of non-responders to dupilumab in clinical practice: a cohort study. J Eur Acad Dermatol Venereol. 2021;3(35):192–4. https://doi.org/10.1111/jdv.16900
  6. Lupardus P.J., Ultsch M., Wallweber H., et al. Structure of the pseudokinase-kinase domains from protein kinase TYK2 reveals a mechanism for Janus kinase (JAK) autoinhibition. Proc Natl Acad Sci USA. 2014;22(111):8025–30. https://doi.org/10.1073/PNAS.1401180111/SUPPL_FILE/PNAS.201401180SI.PDF
  7. Welsch K., Holstein J., Laurence A., et al. Targeting JAK/STAT Signalling in Inflammatory Skin Diseases with Small Molecule Inhibitors. Eur J Immunol. 2017;47:1096–107. https://doi.org/10.1002/eji.201646680
  8. Ferreira S., Guttman-Yassky E., Torres T. Selective JAK1 inhibitors for the treatment of atopic dermatitis: focus on upadacitinib and abrocitinib. Am J Clin Dermatol. 2020;6(21):783–98. https://doi.org/10.1007/s40257-020-00548-6
  9. Samynathan A., Silverberg J.I. Navigating the atopic dermatitis toolbox: Challenging scenarios and shared decision-making. Ann Allergy Asthma Immunol. 2024;132(3):337–43. https://doi.org/10.1016/j.anai.2023.12.020
  10. Атопический дерматит. Клинические рекомендации. Российская ассоциация аллергологов и клинических иммунологов. 2023. [Klinicheskie rekomendacii. Atopicheskij dermatit. Rossijskaya associaciya allergologov i klinicheskih immunologov. 2023 (In Russ.)]. URL: https://raaci.ru›dat›pdf›project_AtD
  11. Veeravalli V., Dash R.P., Thomas J.A., et al. Critical assessment of pharmacokinetic drug–drug interaction potential of tofacitinib, baricitinib and upadacitinib, the three approved Janus kinase inhibitors for rheumatoid arthritis treatment. Drug Safety. 2020;43:711–25. https://doi.org/10.1007/s40264-020-00938-z
  12. Mohamed M.F., Trueman S., Feng T., et al. Characterization of the Effect of Renal Impairment on Upadacitinib Pharmacokinetics. J Clin Pharmacol. 2019;59(6):856–62. https://doi.org/10.1002/jcph.1375
  13. Damsky W., King B.A. JAK inhibitors in dermatology: the promise of a new drug class. J Am Acad Dermatol. 2017;4(76):736–44. https://doi.org/10.1016/J.JAAD.2016.12.005
  14. De Bruin-Weller M., Biedermann T., Bissonnette R., et al. Treat-to-target in atopic dermatitis: an international consensus on a set of core decision points for systemic therapies. Acta Derm Venereol. 2021;101:adv00402. https://doi.org/10.2340/00015555-3751
  15. Reich K., Teixeira H.D., de Bruin-Weller M., et al. Safety and efficacy of upadacitinib in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis (AD Up): results from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2021;397(10290):2169–81. https://doi.org/10.1016/s0140-6736(21)00589-4
  16. Guttman-Yassky E., Teixeira H.D., Simpson E.L., et al. Once-daily upadacitinib versus placebo in adolescents and adults with moderate-to-severe atopic dermatitis (Measure Up 1 and Measure Up 2): results from two replicate double-blind, randomised controlled phase 3 trials. Lancet. 2021;397(10290):2151–68. https://doi.org/10.1016/s0140-6736(21)00588-2
  17. Simpson E.L., Papp K.A., Blauvelt A., et al. Efficacy and safety of upadacitinib in patients with moderate to severe atopic dermatitis: analysis of follow-up data from the Measure Up 1 and Measure Up 2 randomized clinical trials. JAMA. Dermatol. 2022;158(4):404–13. https://doi.org/10.1001/jamadermatol.2022.0029
  18. Silverberg J.I., Gooderham M.J., Paller, A.S., et al. Early and Sustained Improvements in Symptoms and Quality of Life with Upadacitinib in Adults and Adolescents with Moderate-to-Severe Atopic Dermatitis: 52-Week Results from Two Phase III Randomized Clinical Trials (Measure Up 1 and Measure Up 2). Am J Clin Dermatol. 2024;25:485–96. https://doi.org/10.1007/s40257-024-00853-4
  19. Chen T.L., Lee L.L., Huang H., et al. Association of risk of incident venous thromboembolism with atopic dermatitis and treatment with janus kinase inhibitors: A systematic review and meta-analysis. JAMA. Dermatol. 2022;158:1254–61. https://doi.org/10.1001/jamadermatol.2022.3516
  20. Ballanger F., Auffret N., Leccia M.T., et al. Acneiform Lesions but not Acne after Treatment with Janus Kinase Inhibitors: Diagnosis and Management of Janus Kinase-acne. Acta Derm Venereol. 2023;103:adv11657. https://doi.org/10.2340/actadv.v103.11657
  21. Drucker A.M., Morra D.E., Prieto-Merino D., et al. Systemic Immunomodulatory Treatments for Atopic Dermatitis: Update of a Living Systematic Review and Network Meta-analysis. JAMA. Dermatol. 2022;158(5):523–32. https://doi.org/10.1001/jamadermatol.2022.0455
  22. Guttman-Yassky E., Thyssen J.P., Silverberg J., et al. Safety of upadacitinib in moderate-to-severe atopic dermatitis: An integrated analysis of phase 3 studies. J Allergy Clin Immunol. 2023;151(1):172–81. https://doi.org/10.1016/j.jaci.2022.09.023
  23. Edwards S.J., Karner C., Jhita T., et al. Abrocitinib, tralokinumab and upadacitinib for treating moderate-to-severe atopic dermatitis. Health Technol Assess. 2024;28(4):1–113. https://doi.org/10.3310/LEXB9006
  24. Зырянов С.К., Дьяков И.Н., Ильина Н.И. Фармакоэкономический анализ применения упадацитиниба, барицитиниба и дупилумаба для системной терапии пациентов с атопическим дерматитом среднетяжелого и тяжелого течения. Качественная клиническая практика. 2023;(2):70–84. [Zyryanov S.K., Dyakov I.N., Ilina N.I. Pharmacoeconomical analysis of the use of upadacitinib, baricitinib and dupilumab for systemic therapy of patients with moderate and severe atopic dermatitis. Good Clin Pract. 2023;(2):70–84 (In Russ.)]. https://doi.org/10.37489/2588-0519-2023-2-70-84
  25. Shawky A.M., Almalki F.A., Abdalla A.N., et al. A Comprehensive Overview of Globally Approved JAK Inhibitors. Pharmaceutics. 2022;14:1001. https://doi.org/10.3390/pharmaceutics14051001
  26. Wan H., Jia H., Xia T., Zhang D. Comparative efficacy and safety of abrocitinib, baricitinib, and upadacitinib for moderate-to-severe atopic dermatitis: A network meta-analysis. Dermatol Ther. 2022;35(9):e15636. https://doi.org/10.1111/dth.15636
  27. Vestergaard C., Thyssen J.P., Barbarot S., et al. Quality of care in atopic dermatitis – A position statement by the European Task Force on Atopic Dermatitis (ETFAD). J Eur Acad Dermatol Venereol. 2020;34:e136–8. https://doi.org/10.1111/jdv.16092
  28. Pulusani S., Jones E., Throckmorton A. Dermatological Conditions of the Breast. Surg Clin North Am. 2022;102(6):1043–63. https://doi.org/10.1016/j.suc.2022.07.003

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar
2. Figure. Skin lesions in a patient with atopic dermatits: a - in a mammary gland area, b - on the extremities

Baixar (191KB)
Metadados

Declaração de direitos autorais © Bionika Media, 2025