TARGETED BIOLOGICS IN CHILDHOOD ATOPIC DERMATITIS: A COMPREHENSIVE REVIEW OF IMPACT AND INNOVATION
Abstract
Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease in children that significantly impairs their quality of life and can be linked to other allergic disorders. Current treatments for paediatric AD are not always effective, but biologics hold promise as they work on the key factors behind inflammation.
Dupilumab, a fully human monoclonal antibody that inhibits IL-4 and IL-13 signalling by binding to the IL-4 Rα subunit, has shown good efficacy and an acceptable safety profile in treating infants and children with moderate-to-severe AD. It is now registered for the treatment of moderate-to-severe AD in paediatric patients, including young children and infants as young as six months in some regions.
Researchers are continuing to look at how safe and effective dupilumab is for children of different ages with atopic dermatitis, and whether starting treatment early can change how the disease develops over time. Other biologic treatments such as tralokinumab (which blocks IL-13), lebrikizumab, nemolizumab, tezepelumab, and JAK inhibitors are also being studied, and some have already been approved for use in children. Together, these therapies are expanding the options available for managing paediatric AD. In this review, we highlight the latest evidence on biologics in children, focusing on how they work, how well they control disease, and what is known about their safety, to help support treatment decisions in practice.
Aim of Study: We aim to review current understanding of atopic dermatitis and the latest developments in targeted therapies, including biologics and small-molecule inhibitors, based on clinical trial findings.
References
Al-Naqeeb J, Danner S, Fagnan LJ, et al. The burden of child-hood atopic dermatitis in the primary care setting: a report from the Meta-LARC Consortium. J Am Board Fam Med. 2019;32(2):191–200. https:// doi.org/ 10.3122/ jabfm. 2019. 02. 180225.
Alexander T, Maxim E, Cardwell LA, Chawla A, Feldman SR. Prescriptions for atopic dermatitis: oral corticosteroids remain commonplace. J Dermatolog Treat. 2018;29(3):238–40. doi: 10.1080/09546634.2017.1365112
Alexis Tracy, SafiyyahBhatti, Lawrence F. Eichenfield. Update on Pediatric Atopic Dermatitis, Cutis. 2020 Sep;106(3):143-146. DOI: 10.12788/cutis.0077
Amy S. Palle, Elaine C. Siegfried, Eric L. Simpson, Michael J. Cork, Robert Sidbury, Iris H. Chen, Faisal A. Khokha, Jing Xiao, Ariane DubostBrama, Ashish Bansal. Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 OpenLabel Extension Study. American Journal of Clinical Dermatology (2024) 25:655–668. https://doi.org/10.1007/s40257-024-00859-y
Annie George, Rafael Paolo Lansang, BHS, PerlaLansang and Melinda Gooderham. A Practical Guide to Using Biologics in Pediatric Dermatology. Journal of Cutaneous Medicine and Surgery 2024, Vol. 28(1) 59–67. DOI:10.1177/12034754231222415 jcms.sagepub.com
Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis.JAKSTAT. 2013;2(3):e24137. https:// doi.org/ 10.4161/ jkst. 24137.
Barbara Klasa, Ewa Cichocka-Jarosz. ATOPIC DERMATITIS – CURRENT STATE OF RESEARCH ON BIOLOGICAL TREATMENT. Journal of Mother and Child 24(1) 2020 53-66. doi: 10.34763/jmotherandchild.2020241.2003.0000010
Barrett J. Fda approves dupilumab for atopic dermatitis in children. drug topics; 2020 Available from: https://www.drugtopics.com/autoimmune-diseases/fda-approves-dupilumab-atopic-dermatitis-children [2020, May 27].
Beck LA, Thaçi D, Hamilton Jd, Graham nM, Bieber t, rocklin r, et al. dupilumab treatment in adults with moderate-to-severe atopic dermatitis. nengl J Med 2014;371:130–9.
Bin L, Leung DY. Genetic and epigenetic studies of atopic der-matitis. Allergy Asthma ClinImmunol. 2016;12:52. https:// doi.org/ 10.1186/ s13223- 016- 0158-5.
Boguniewicz M, Fonacier L, Guttman-Yassky E, Ong PY, Silver-berg J, Farrar JR. Atopic dermatitis yardstick: Practical recom-mendations for an evolving therapeutic landscape. Ann Allergy Asthma Immunol. 2018;120(1):10-22.e2. https:// doi.org/ 10.1016/j. anai. 2017. 10. 039.
Bylund S, von Kobyletzki LB, Svalstedt M, Svensson A. Preva-lence and incidence of atopic dermatitis: a systematic review. ActaDermVenereol. 2020;100(12):adv00160. https:// doi.org/ 10.2340/ 00015 555- 3510.
Camille Rothenberg-Lausell, Jonathan Bar, Dante Dahabreh, Yael Renert-Yuval, Ester Del Duca and Emma Guttman-Yassky. Biologic and small-molecule therapy for treating moderate to severe atopic dermatitis: Mechanistic considerations. J Allergy ClinImmunol. 2024 Jul;154(1):20-30. DOI: 10.1016/j.jaci.2024.04.009
Zhou B, Peng C, Cao Q, Wang J, Chen X, Li J. Dupilumab therapy in children aged 2-12 years with uncontrolled moderate-to-severe atopic dermatitis: a Chinese real-world study. J EurAcadDermatolVenereol. 2023;38(1):e35–e38. doi:10.1111/jdv.19409
Chung J, Simpson EL. The socioeconomics of atopic dermatitis.Ann Allergy Asthma Immunol. 2019;122(4):360–6. https:// doi.org/ 10.1016/j. anai. 2018. 12. 017.
Cork MJ, Danby SG, Ogg GS. Atopic dermatitis epidemiol-ogy and unmet need in the United Kingdom.J Dermatol Treat. 2019;8:801–9. https:// doi.org/ 10.1080/ 09546 634. 2019. 16551 37.
Cork MJ, Thaçi D, Eichenfield LF, 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;182:85‐96.
Drucker AM, Wang AR, Li WQ, Sevetson E, Block JK, Qureshi AA. The burden of atopic dermatitis: summary of a report for the National Eczema Association. J InvestigDermatol. 2017;137(1):26–30. https:// doi.org/ 10.1016/j. jid. 2016. 07. 012.
Eichenfield LF, Tom WL, Chamlin SL, et al. Guidelines of care for the management of atopic dermatitis: section 1. Diagnosis and assessment of atopic dermatitis. J Am AcadDermatol. 2014;70(2):338–51. https:// doi.org/ 10.1016/j. jaad. 2013. 10. 010.
European Medicines Agency (EMA). DUPIXENT® (dupilumab). Summary of opinion (post-authorisation).2023. https:// www.ema. europa. eu/ en/ documents/ smop/ chmp- post- authorisat ion- summa ry- posit ive- opini on- dupixent- ii- 60_ en. pdf. Accessed 27 Feb 2023.
Frazier W, Bhardwaj N. Atopic dermatitis: diagnosis and treatment. Am Fam Physician. 2020;101(10):590–8.
Futamura M, Leshem YA, Thomas KS, Nankervis H, Williams HC, Simpson EL. A systematic review of Investigator Global Assessment (IGA) in atopic dermatitis (AD) trials: many options, no standards. J Am AcadDermatol. 2016;74(2):288–94. https:// doi.org/10.1016/j.jaad.2015.09.062.
Thaçi D, Simpson EL, Beck LA, Bieber T, Blauvelt A, Papp K, et al. Efficacy and safety of dupilumab in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical treatments: a randomised, placebo-controlled, dose-ranging phase 2b trial. Lancet 2016;387:40–52.
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. [PubMed: 31407311]
Guttman-Yassky E, Thaçi D, Pangan AL, Hong HC, Papp KA, Reich K, et al. Upadacitinib in adults with moderate to severe atopic dermatitis: 16-week results from a randomized, placebocontrolled trial. J Allergy ClinImmunol. 2020;145(3):877–84. doi: 10.1016/j.jaci.2019.11.025.
Halling AS, Loft ND, Silverberg JI, Guttman-Yassky E, Thyssen JP. Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis. J Am AcadDermatol. 2020.
Le-Floc’h A, Allinne J, Nagashima K, Scott G, Birchard D, Asrat S, et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflamma-tion. Allergy. 2020;75(5):1188–204. https:// doi.org/ 10.1111/ all. 14151.
Nakagawa H, Nemoto O, Igarashi A, et al. Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis. J Allergy ClinImmunol. 2019;144:1575‐1583.
Paller AS, Simpson EL, Siegfried EC, Cork MJ, Wollenberg A, Arkwright PD, et al. Dupilumab in children aged 6 months to younger than 6 years with uncontrolled atopic dermatitis: a randomised, double-blind, placebo-controlled, phase 3 trial. Lan-cet. 2022;400(10356):908–19. https:// doi.org/ 10.1016/ S0140- 6736(22) 01539-2.
Patruno C, Fabbrocini G, Lauletta G, et al. A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years. J Dermatol Treatment. 2023;34(1):2246602. doi:10.1080/09546634.2023.2246602
Popovic B, Breed J, Rees DG, Gardener MJ, Vinall LM, Kemp B, et al. Structural Characterisation Reveals Mechanism of IL-13-Neutralising Monoclonal Antibody Tralokinumab as Inhibition of Binding to IL-13Rα1 and IL-13Rα2. J Mol Biol. 2017;429(2):208–19. [PubMed: 27956146]
Radi G, Simonetti O, Rizzetto G, Diotallevi F, Molinelli E, Offidani A. Baricitinib: The First Jak Inhibitor Approved in Europe for the Treatment of Moderate to Severe Atopic Dermatitis in Adult Patients. Healthcare (Basel). 2021;9(11)
Riccardo Castagnoli, Maria de Filippo, Martina Votto, AlessiaMarseglia, LorenzaMontagna, Gian Luigi Marseglia, Amelia Licari. An update on biological therapies for pediatric allergic diseases. Minerva Pediatrica 2020 October;72(5):364-71. DOI: 10.23736/S0026-4946.20.05993-9
Safety, pharmacokinetics and efficacy of dupilumab in patients ≥6 months to <6 Years With Moderate-to-Severe Atopic Dermatitis (liberty AD preschool). Clinical Trials; 2017 [InterneAvailable from: https://clinicaltrials.gov/ct2/show/NCT03346434 [ 2020, Jan 19]
Sarıcaoğlu H, Yazici S, Zorlu Ö, BülbülBaşkan E, Aydoğan K. Cyclosporine-A for severe childhood atopic dermatitis: clinical experience on efficacy and safety profile. Turk J Med Sci. 2018;48(5):933–8. doi: 10.3906/sag-1711-7
Silverberg JI, Barbarot S, Gadkari A, et al. Epidemiology of atopic dermatitis in children aged 6–11 years: a cross-sectional study in the United States (US), Canada, Europe, and Japan. Paper presented at: American Academy of Dermatology Annual Meeting; March 20-24, 2020; Denver, CO.
Silverberg JI, Guttman-Yassky E, Thaçi D, Irvine AD, Stein Gold L, Blauvelt A, et al. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis.N Engl J Med 2023;388:1080-91.
Simpson E L, Pallera S, Siegfried E C, Boguniewicz M, Sher L, Gooderham MJ, et al. Efficacy and Safety of Dupil-umab in adolescents With Uncontrolled Moderate to Severe atopic dermatitis: a Phase 3 randomized clinical trial. JaMadermatol 2019;156:44–56.
Simpson EL, PalleraS, Siegfried EC, Boguniewicz M, Sher L, Gooderham MJ, et al. Efficacy and Safety of Dupil-umab in adolescents With Uncontrolled Moderate to Severe atopic dermatitis: a Phase 3 randomized clinical trial. JaMadermatol 2019;156:44–56.
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 AcadDermatol 2019;80:1013-21.
Simpson EL, Sinclair R, Forman S, et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial. Lancet. 2020;396:255-266.
Sneha Butala, Leslie Castelo-Soccio, Rishi Seshadri, Eric L. Simpson, John J O’Shea, Thomas Bieber, Amy S. Paller, MS, MD. Biologic versus small molecule therapy for treating moderate to severe atopic dermatitis: clinical considerations. J Allergy ClinImmunolPract. 2023 May ; 11(5): 1361–1373. doi:10.1016/j.jaip.2023.03.011
Study to assess the long-term safety of dupilumab administered in participants ≥6 months to<18 Years of Age With Atopic Dermatitis (AD) ClinicalTrials.gov ID NCT02612454
Taieb Y, Baum S, Ben Amitai D, Barzilai A, Greenberger S. The use of methotrexate for treating childhood atopic dermatitis: A multicenter retrospective study. J Dermatolog Treat. 2019;30(3):240– 4. doi: 10.1080/09546634.2018.1508816
Thanaporn Ratchataswan, MDA, Tina M. Banzon, MDA,E, Jacob P. Thyssen, MD, PhD, DmSciB, Stephan Weidinger, MD, PhD, MaHMC, Emma Guttman-Yassky, MD, PhDD, Wanda Phipatanakul, MD, MSA,E. Biologics for Treatment of Atopic Dermatitis: Current Status and Future Prospect. J Allergy ClinImmunolPract. 2021 March ; 9(3): 1053–1065. doi:10.1016/j.jaip.2020.11.034
Copyright (c) 2025 Darya Lazitskaya, Dmytro Kowalczuk, Mykola Sobchynskyi, Andrzej Myrny, Wiktoria Kasianik, Kamil Turlej, Valeryia Milasheuskaya, Iga Kiełbaszewska, Natalia Surosz, Katsiaryna Miraniuk, Dawid Wiczkowski
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
