Current Updates on Moderate to Severe Atopic Dermatitis Management: From Pathogenesis to Breakthrough Treatment

Authors

  • Muhammad Alifian Remifta Putra Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta
  • Vincent Kharisma Wangsaputra Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta
  • Raya Makarim Penantian Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta

DOI:

https://doi.org/10.55175/cdk.v51i7.1096

Keywords:

Atopic dermatitis, monoclonal antibody, therapy

Abstract

Atopic dermatitis (AD), characterized by recurrent eczematous lesions and pruritus, is a major contributor to the total global burden of disability. The common management practice includes patient education and topical emollients and is heavily reliant on the use of anti-inflammatory agents with systemic corticosteroids. Monoclonal antibodies provide a novel, targeted approach towards specific cytokines. This study aims to highlight the novel systemic therapeutic drug aimed at specific targets. A comprehensive literature review utilizes databases including EMBASE, EBSCOhost, PubMed, Scopus, and Wiley Online Library, using keywords: “monoclonal antibody” AND “therapy” AND “atopic dermatitis”. Relevant papers containing different updates in atopic dermatitis management and the utilization of monoclonal antibodies are included in this review. The current regimen of monoclonal antibodies offers better management of moderate-to-severe AD. Monoclonal antibodies have become a promising therapy as they demonstrate better therapeutic effects in terms of skin barrier protection and anti-inflammatory and pruritusreducing effects. However, its application still faces various challenges such as side effects and infections. The heterogeneity and relapsing nature also add to the complexity and risk profile of AD management.

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References

Hadi HA, Tarmizi AI, Khalid KA, Gajdacs M, Aslam A, Jamshed S. The epidemiology and global burden of atopic dermatitis: A narrative review. Life (Basel) 2021;11(9):936.

Kaufman BP, Guttman-Yassky E, Alexis AF. Atopic dermatitis in diverse racial and ethnic groups-variations in epidemiology, genetics, clinical presentation, and treatment. Exp Dermatol. 2018;27:340–57.

Bylund S, Kobyletzki L, Svalstedt M, Svensson A. Prevalence and incidence of atopic dermatitis: A systematic review. Acta Dermato Venereologica 2020;100(12):320-9.

Lopez Carrera YI, Al Hammadi A, Huang YH, Llamado LJ, Mahgoub E, Tallman AM. Epidemiology, diagnosis, and treatment of atopic dermatitis in the developing countries of Asia, Africa, Latin America, and the Middle East: A review. Dermatol Ther (Heidelb). 2019; 9(4):685–705.

Rerknimitr P, Otsuka A, Nakashima C, Kabashima K. The etiopathogenesis of atopic dermatitis: Barrier disruption, immunological derangement, and pruritus. Inflamm Regenerat. 2017;37(1):1-15.

Oninla OA, Akinkugbe AO, Otike-Odibi BI, Oripelaye MM, Olanrewaju FO. Atopic dermatitis in adults: Epidemiology, risk factors, pathogenesis, clinical features, and management [Internet]. 2021. Available from: https://www.intechopen.com/chapters/76331.

Alexander H, Patton T, Jabbar-Lopez Z, Manca A, Flohr C. Novel systemic therapies in atopic dermatitis: What do we need to fulfil the promise of a treatment revolution? F1000Res. 2019;8:132.

Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD.. Atopic dermatitis. Nat Rev Dis Primers. 2018;4:1.

He R, Oyoshi MK, Wang JYT, Hodge MR, Jin H, Geha RS. The prostaglandin D₂ receptor CRTH2 is important for allergic skin inflammation after epicutaneous antigen challenge. J Allerg Clin Immunol. 2010;126(4):784-90.

Moosbrugger-Martinz V, Leprince C, Mechin MC, Simon M, Blunder S, Gruber R, et al. Revisiting the roles of filaggrin in atopic dermatitis. Int J Mol Sci. 2022;23(10):5318.

Patel N, Feldman SR. Management of atopic dermatitis. Springer: Advances in Experimental Medicine and Biology; 2017. p. 105–37.

Souto EB, Dias-Ferreira J, Oliveira J, Sanchez-Lopez E, Lopez-Machado A, Espina M, et al. Trends in atopic dermatitis-from standard pharmacotherapy to novel drug delivery systems. Int J Mol Sci. 2019;20(22):5659.

Kowalska-Oledzka E, Czarnecka M, Baran A. Comparison of treatment standards in atopic dermatitis management across selected geographies prior to emerging targeted therapies onset. J Drug Assess. 2019;8(1):122–5.

Carr WW. Topical calcineurin inhibitors for atopic dermatitis: Review and treatment recommendations. Pediatr Drugs 2013;15(4):303–10.

Crissinger A, Nguyen NV. The use of topical calcineurin inhibitors in atopic dermatitis. Open Dermatol J. 2014;8:12-7.

Johnson BB, Franco AI, Beck LA, Prezzano JC. Treatment-resistant atopic dermatitis: Challenges and solutions. Clin Cosmet Investig Dermatol. 2019;12:181–92J.

Li H, Zuo J, Tang W. Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases. Front Pharmacol. 2018;9:1048.

He A, Feldman SR, Fleischer AB Jr. An assessment of the use of antihistamines in the management of atopic dermatitis. J Am Acad Dermatol. 2018;79(1):92-6.

Drucker AM, Ellis AG, Bohdanowicz M, Mashayekhi S, Yiu ZZN, Rochwerg B, et al. Systemic immunomodulatory treatments for patients with atopic dermatitis: A systematic review and network meta-analysis. JAMA Dermatol. 2020;156(6):659-67.

Drucker AM, Morra DE, Prieto-Merino D, Ellis AG, Yiu ZZN, Rochwerg B, 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.

Ariens LFM, Bakker DS, van der Schaft J, Garritsen FM, Thijs JL, de Bruin-Weller MS, et al. Dupilumab in atopic dermatitis: Rationale, latest evidence, and place in therapy. Ther Adv Chronic Dis. 2018;9(9):159–70.

Cork MJ, Thaci D, Eichenfield LF, Arkwright PD, Hultsch T, Davis JD, et al. Dupilumab in adolescents with uncontrolled moderate-to-severe atopic dermatitis: Results from a phase IIa open-label trial and subsequent phase III open-label extension. Br J Dermatol. 2020;82:85–96.

A phase II study to evaluate the safety and efficacy of AK120 in subjects with moderate to severe atopic dermatitis [Internet]. [cited 2023 Jul 22]. Available from: https://clinicaltrials.gov/study/NCT06092762?cond=NCT06092762&rank=1.

Paller AS, Flohr C, Cork M, Bewley A, Blauvelt A, Hong HC, et al. Efficacy and safety of tralokinumab in adolescents with moderate to severe atopic dermatitis: The phase 3 ECZTRA 6 randomized clinical trial. JAMA Dermatol. 2023;159(6):596–605.

Simpson EL, Merola JF, Silverberg JI, Reich K, Warren RB, Staumont-Salle D, et al. Safety of tralokinumab in adult patients with moderate-to-severe atopic dermatitis: Pooled analysis of five randomized, double-blind, placebo-controlled phase II and phase III trials. Br J Dermatol. 2022;187:888-99.

Cevikbas F, Ward A, Firth C, Veverka K. Eblasakimab, a novel IL-13 receptor alpha 1 monoclonal antibody, blocks STAT6 phosphorylation with low dose in human volunteers. Clin Immunol. 2023;253:109677.

Silverberg JI, Pinter A, Pulka G, Poulin Y, Bouaziz JD, Wollenberg A, et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus. J Allerg Clin Immunol. 2020;145(1):173-82.

Kabashima K, Matsumura T, Komazaki H, Kawashima M; Nemolizumab-JP01 Study Group. Trial of nemolizumab and topical agents for atopic dermatitis with pruritus. N Engl J Med. 2020;383(2):141–50.

Renert-Yuval Y, Guttman-Yassky E. Monoclonal antibodies for the treatment of atopic dermatitis. Curr Opin Allerg Clin Immunol. 2018;18(4):356-64.

Patel PM, Jones VA, Kridin K, Amber KT. The role of dipeptidyl peptidase-4 in cutaneous disease. Exp Dermatol. 2021;30:304–18

Guttman-Yassky E, Blauvelt A, Eichenfield LF, Paller AS, Armstrong AW, Drew J, et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: A phase 2b randomized clinical trial. JAMA Dermatol. 2020;156(4):411-20.

Bashrahil B, Alzahrani Z, Samarkandy S, Aman A, Jfri A. The efficacy and safety of lebrikizumab monotherapy for the management of moderate-to-severe atopic dermatitis: A systematic review and meta-analysis. Front Med. 2023;9:1091271.

Simpson EL, Parnes JR, She D, Crouch S, Rees W, Mo M, et al. Tezepelumab, an anti-thymic stromal lymphopoietin monoclonal antibody, in the treatment of moderate to severe atopic dermatitis: A randomized phase 2a clinical trial. J Am Acad Dermatol. 2019;80(4):1013-21.

Renert-Yuval Y, Guttman-Yassky E. New treatments for atopic dermatitis targeting beyond IL-4/IL-13 cytokines. Ann Allerg Asthma Immunol. 2019;124(1):28-35.

Furue M, Furue M. OX40L-OX40 signaling in atopic dermatitis. J Clin Med. 2021;10(12):2578.

Guttman-Yassky E, Pavel AB, Zhou L, Estrada YD, Zhang N, Xu H, et al. GBR 830, an anti-OX40, improves skin gene signatures and clinical scores in patients with atopic dermatitis. J Allerg Clin Immunol. 2019;144(2):482-93.

Guttman-Yassky E, Simpson EL, Reich K, Kabashima K, Igawa K, Suzuki T, et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: A multicentre, double-blind, placebo-controlled phase 2b study. Br J Dermatol. 2023;401(10372): 204-14.

Weidinger S, Bieber T, Cork MJ, Reich A, Wilson R, Quaratino S, et al. Safety and efficacy of amlitelimab, a fully human, non-depleting, non-cytotoxic anti-OX40Ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomised placebo-controlled trial. Br J Dermatol. 2023 Oct 25;189(5):531-9.

Londei M, Kenney B, Los G, Marino MH. A phase 1 study of ANB020, an anti-IL-33 monoclonal antibody, in healthy volunteers. J Am Acad Dermatol. 2017;76(6):20.

Guttman-Yassky E, Brunner PM, Neumann AU, Khattri S, Pavel AB, Malik K, et al. Efficacy and safety of fezakinumab (an IL-22 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by conventional treatments: A randomized, double-blind, phase 2a trial. J Am Acad Dermatol. 2018;78(5):872-881.e6.

Saeki H, Kabashima K, Tokura Y, Murata Y, Shiraishi A, Tamamura R, et al. Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: A randomized, double-blind, placebo-controlled, phase II study. British Journal of Dermatology 2017 Aug;177(2):419-27.

Sugaya M. The role of Th17-related cytokines in atopic dermatitis. Internat J Mole Sci. 2020;21(4):1314.

Bieber T. Atopic dermatitis: An expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022;21:21–40.

Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017;76(4):736-44.

Shawky AM, Almalki FA, Abdalla AN, Abdelazeem AH, Gouda AM. A comprehensive overview of globally approved JAK Inhibitors. Pharmaceutics 2022 May 6;14(5):1001.

Chovatiya R, Paller AS. JAK inhibitors in the treatment of atopic dermatitis. J Allerg Clin Immunol. 2021;148(4):927–40.

Schaper-Gerhardt K, Rossbach K, Nikolouli E, Werfel T, Gutzmer R, Mommert S. The role of the histamine H4 receptor in atopic dermatitis and psoriasis. Br J Pharmacol. 2020;177(3):490-502.

Simpson EL, Gooderham M, Wollenberg A, Weidinger S, Armstrong A, Soung J, et al. Efficacy and safety of lebrikizumab in combination with topical corticosteroids in adolescents and adults with moderate-to-severe atopic dermatitis: A randomized clinical trial (Adhere). JAMA Dermatol. 2023;159(2):182–91.

Katoh N, Ohya Y, Ikeda M, Ebihara T, Katayama I, Saeki H, et al. Clinical practice guidelines for the management of atopic dermatitis 2018. J Dermatol. 2019;46:1053-101.

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Published

01-07-2024

How to Cite

Putra, M. A. R., Wangsaputra, V. K., & Penantian, R. M. (2024). Current Updates on Moderate to Severe Atopic Dermatitis Management: From Pathogenesis to Breakthrough Treatment. Cermin Dunia Kedokteran, 51(7), 400–408. https://doi.org/10.55175/cdk.v51i7.1096