Interleukin antagonists for atopic dermatitis: a new era of therapy

REFERENCES

• Bylund S, Von Kobyletzki LB, Svalstedt M, et al. Prevalence and incidence of atopic dermatitis: a systematic review. Acta Derm Venereol. 2020;100(12):320–329. doi: 10.2340/00015555-3510
   Google Scholar
• Wollenberg A, Barbarot S, Bieber T, 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):657–682. doi: 10.1111/jdv.14891
   PubMed Web of Science ®Google Scholar
• Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014;71(2):327–349. doi: 10.1016/j.jaad.2014.03.030
   PubMed Web of Science ®Google Scholar
• Zhou S, Qi F, Gong Y, et al.. Biological Therapies for Atopic Dermatitis: A Systematic Review. Dermatology. 2021;237(4):542–552. doi: 10.1159/000514535
   PubMed Web of Science ®Google Scholar
• Ferrucci SM, Tavecchio S, Marzano AV, et al. Emerging systemic treatments for atopic dermatitis. Dermatol Ther (Heidelb). 2023;13(5):1071–1081. doi: 10.1007/s13555-023-00920-4
   PubMed Web of Science ®Google Scholar
• Bieber T Atopic dermatitis: an expanding therapeutic pipeline for a complex disease. Nat Rev Drug Discov. 2022 Jan;21(1):21–40. 10.1038/s41573-021-00266-6
   PubMed Web of Science ®Google Scholar
• Dubin C, Del Duca E, Guttman-Yassky E The IL-4, IL-13 and IL-31 pathways in atopic dermatitis. Expert Rev Clin Immunol. 2021;17(8):835–852. 10.1080/1744666X.2021.1940962
   PubMed Web of Science ®Google Scholar
• Makowska K, Nowaczyk J, Blicharz L, et al. Immunopathogenesis of atopic dermatitis: focus on Interleukins as disease drivers and therapeutic targets for novel treatments. Int J Mol Sci. 2023;24(1):781. doi: 10.3390/ijms24010781.
   PubMed Web of Science ®Google Scholar
• Tsoi LC, Rodriguez E, Degenhardt F, et al. Atopic Dermatitis Is an IL-13-Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis. J Invest Dermatol. 2019;139(7):1480–9.
   PubMed Web of Science ®Google Scholar
• Szegedi K, Lutter R, Res PC, et al. Cytokine profiles in interstitial fluid from chronic atopic dermatitis skin. J Eur Acad Dermatol Venereol [Internet]. 2015;29(11):2136–2144.10.1111/jdv.13160
   PubMed Web of Science ®Google Scholar
• Vollenweider S, Saurat JH, Röcken M, et al. Evidence suggesting involvement of interleukin-4 (IL-4) production in spontaneous in vitro IgE synthesis in patients with atopic dermatitis. J Allergy Clin Immunol. 1991;87(6):1088–95.
   PubMed Web of Science ®Google Scholar
• Fish SC, Donaldson DD, Goldman SJ, et al. IgE generation and mast cell effector function in mice deficient in IL-4 and IL-13. J Immunol. 2005;174(12):7716–7724. doi: 10.4049/jimmunol.174.12.7716
   PubMed Web of Science ®Google Scholar
• Khurana Hershey GK. IL-13 receptors and signaling pathways: An evolving web. J Allergy Clin Immunol. 2003;111(4):677–90.
   PubMed Web of Science ®Google Scholar
• Puri RK. Structure and function of interleukin-4 and its receptor. Cancer Treat Res. 1995;80:143–85.
   PubMedGoogle Scholar
• Omori-Miyake M, Yamashita M, Tsunemi Y, et al. In vitro assessment of IL-4- or IL-13-mediated changes in the structural components of keratinocytes in mice and humans. J Invest Dermatol. 2014;134(5):1342–1350. doi: 10.1038/jid.2013.503
   PubMed Web of Science ®Google Scholar
• Berdyshev E, Goleva E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3(4):e98006. doi: 10.1172/jci.insight.98006
   PubMed Web of Science ®Google Scholar
• Leung DYM. Clinical implications of new mechanistic insights into atopic dermatitis. Curr Opin Pediatr. 2016;28(4):456–462. doi: 10.1097/MOP.0000000000000374
   PubMed Web of Science ®Google Scholar
• Novak N, Leung DYM. Advances in atopic dermatitis. Curr Opin Immunol. 2011;23(6):778–783. doi: 10.1016/j.coi.2011.09.007
   PubMed Web of Science ®Google Scholar
• Kim BE, Leung DY, Boguniewicz M, et al. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008;126(3):332–7.
   PubMed Web of Science ®Google Scholar
• Howell MD, Fairchild HR, Kim BE, et al. Th2 cytokines act on S100/A11 to downregulate keratinocyte differentiation. J Invest Dermatol. 2008;128(9):2248–2258. doi: 10.1038/jid.2008.74
   PubMed Web of Science ®Google Scholar
• Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2007;120(1):150–155. doi: 10.1016/j.jaci.2007.04.031
   PubMed Web of Science ®Google Scholar
• Nguyen JK, Austin E, Huang A, et al. The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets. Arch Dermatol Res. 2020;312(2):81–92. doi: 10.1007/s00403-019-01972-3
   PubMed Web of Science ®Google Scholar
• Oh M-H, Oh SY, Yu J, et al. IL-13 induces skin fibrosis in atopic dermatitis by thymic stromal lymphopoietin. J Immunol. 2011;186(12):7232–7242. doi: 10.4049/jimmunol.1100504
   PubMed Web of Science ®Google Scholar
• Yoshikawa M, Nakajima T, Tsukidate T, et al. TNF-α and IL-4 regulate expression of IL-13 receptor α2 on human fibroblasts. Biochem Biophys Res Commun. 2003;312(4):1248–1255. doi: 10.1016/j.bbrc.2003.11.077
   PubMed Web of Science ®Google Scholar
• Oiso N, Fukai K, Ishii M. Interleukin 4 receptor alpha chain polymorphism Gln551Arg is associated with adult atopic dermatitis in Japan. Br J Dermatol. 2000;142(5):1003–6.
   PubMed Web of Science ®Google Scholar
• Shang H, Cao XL, Wan YJ, et al. IL-4 Gene Polymorphism May Contribute to an Increased Risk of Atopic Dermatitis in Children. Dis Markers. 2016;2016:1021942.
   PubMed Web of Science ®Google Scholar
• Hummelshoj T, Bodtger U, Datta P, et al. Association between an interleukin-13 promoter polymorphism and atopy. Eur J Immunogenet. 2003;30(5):355–9.
   PubMedGoogle Scholar
• Lesiak A, Kuna P, Zakrzewski M, et al. Combined occurrence of filaggrin mutations and IL-10 or IL-13 polymorphisms predisposes to atopic dermatitis. Exp Dermatol. 2011;20(6):491–495. doi: 10.1111/j.1600-0625.2010.01243.x
   PubMed Web of Science ®Google Scholar
• Namkung JH, Lee JE, Kim E, et al. Association of polymorphisms in genes encoding IL-4, IL-13 and their receptors with atopic dermatitis in a Korean population. Exp Dermatol. 2011;20(11):915–919. doi: 10.1111/j.1600-0625.2011.01357.x
   PubMed Web of Science ®Google Scholar
• Bağci IS, Ruzicka T. IL-31: a new key player in dermatology and beyond. J Allergy Clin Immunol. 2018;141(3):858–866. doi: 10.1016/j.jaci.2017.10.045
   PubMed Web of Science ®Google Scholar
• Sonkoly E, Muller A, Lauerma AI, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117(2):411–417. doi: 10.1016/j.jaci.2005.10.033
   PubMed Web of Science ®Google Scholar
• Rabenhorst A, Hartmann K. Interleukin-31: a novel diagnostic marker of allergic diseases. Curr Allergy Asthma Rep. 2014;14(4):423. doi: 10.1007/s11882-014-0423-y
   PubMed Web of Science ®Google Scholar
• Furue M, Yamamura K, Kido-Nakahara M, et al.. Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis. Allergy. 2018;73(1):29–36. doi: 10.1111/all.13239
   PubMed Web of Science ®Google Scholar
• Arai I, Tsuji M, Takeda H, et al. A single dose of interleukin-31 (IL-31) causes continuous itch-associated scratching behaviour in mice. Exp Dermatol. 2013;22(10):669–671. doi: 10.1111/exd.12222
   PubMed Web of Science ®Google Scholar
• Bilsborough J, Leung DYM, Maurer M, et al. IL-31 is associated with cutaneous lymphocyte antigen-positive skin homing T cells in patients with atopic dermatitis. J Allergy Clin Immunol. 2006;117(2):418–25.
   PubMed Web of Science ®Google Scholar
• Feld M, Garcia R, Buddenkotte J, et al. The pruritus- and TH2-associated cytokine IL-31 promotes growth of sensory nerves. J Allergy Clin Immunol. 2016;138(2):500–8.e24. doi: 10.1016/j.jaci.2016.02.020
   PubMed Web of Science ®Google Scholar
• Kasraie S, Niebuhr M, Baumert K, et al.. Functional effects of interleukin 31 in human primary keratinocytes. Allergy. 2011;66(7):845–852. doi: 10.1111/j.1398-9995.2011.02545.x
   PubMed Web of Science ®Google Scholar
• Steinhoff M, Bienenstock J, Schmelz M, et al. Neurophysiological, neuroimmunological, and neuroendocrine basis of pruritus. J Invest Dermatol. 2006;126(8):1705–1718. doi: 10.1038/sj.jid.5700231
   PubMed Web of Science ®Google Scholar
• Takamori A, Nambu A, Sato K, et al. IL-31 is crucial for induction of pruritus, but not inflammation, in contact hypersensitivity. Sci Rep. 2018;8(1):6639. doi: 10.1038/s41598-018-25094-4
   PubMedGoogle Scholar
• Oyama S, Kitamura H, Kuramochi T, et al. Cynomolgus monkey model of interleukin-31-induced scratching depicts blockade of human interleukin-31 receptor a by a humanized monoclonal antibody. Exp Dermatol. 2018;27(1):14–21. doi: 10.1111/exd.13236
   PubMed Web of Science ®Google Scholar
• Ezzat MHM, Hasan ZE, Shaheen KYA. Serum measurement of interleukin-31 (IL-31) in paediatric atopic dermatitis: elevated levels correlate with severity scoring. J Eur Acad Dermatol Venereol. 2011;25(3):334–339. doi: 10.1111/j.1468-3083.2010.03794.x
   PubMed Web of Science ®Google Scholar
• Raap U, Wichmann K, Bruder M, et al. Correlation of IL-31 serum levels with severity of atopic dermatitis. J Allergy Clin Immunol. 2008;122(2):421–423. doi: 10.1016/j.jaci.2008.05.047
   PubMed Web of Science ®Google Scholar
• Neis MM, Peters B, Dreuw A, et al. Enhanced expression levels of IL-31 correlate with IL-4 and IL-13 in atopic and allergic contact dermatitis. J Allergy Clin Immunol. 2006;118(4):930–937. doi: 10.1016/j.jaci.2006.07.015
   PubMed Web of Science ®Google Scholar
• Hayashida S, Uchi H, Takeuchi S, et al. Significant correlation of serum IL-22 levels with CCL17 levels in atopic dermatitis. J Dermatol Sci. 2011;61(1):78–79. doi: 10.1016/j.jdermsci.2010.08.013
   PubMed Web of Science ®Google Scholar
• Jin M, Yoon J. From bench to clinic: The potential of therapeutic targeting of the IL-22 signaling pathway in atopic dermatitis. Immune Netw. 2018;18(6):1–11. doi: 10.4110/in.2018.18.e42
   Web of Science ®Google Scholar
• Scriba TJ, Kalsdorf B, Abrahams D-A, et al. Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol. 2008;180(3):1962–1970. doi: 10.4049/jimmunol.180.3.1962
   PubMed Web of Science ®Google Scholar
• Eyerich S, Eyerich K, Pennino D, et al. Th22 cells represent a distinct human T cell subset involved in epidermal immunity and remodeling. J Clin Invest. 2009;119(12):3573–3585. doi: 10.1172/JCI40202
   PubMed Web of Science ®Google Scholar
• Akdis M, Palomares O, Van De Veen W, et al. TH17 and TH22 cells: a confusion of antimicrobial response with tissue inflammation versus protection. J Allergy Clin Immunol. 2012;129(6):1438–1449. doi: 10.1016/j.jaci.2012.05.003
   PubMed Web of Science ®Google Scholar
• Nograles KE, Zaba LC, Guttman-Yassky E, et al. Th17 cytokines interleukin (IL)-17 and IL-22 modulate distinct inflammatory and keratinocyte-response pathways. Br J Dermatol. 2008;159(5):1092–102.
   PubMed Web of Science ®Google Scholar
• Nograles KE, Zaba LC, Shemer A, et al. IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells. J Allergy Clin Immunol. 2009;123(6): 1244–52.e2.
   PubMed Web of Science ®Google Scholar
• Tamagawa-Mineoka R, Okuzawa Y, Masuda K, et al. Increased serum levels of interleukin 33 in patients with atopic dermatitis. J Am Acad Dermatol. 2014;70(5):882–888. doi: 10.1016/j.jaad.2014.01.867
   PubMed Web of Science ®Google Scholar
• Salimi M, Barlow JL, Saunders SP, et al. A role for IL-25 and IL-33-driven type-2 innate lymphoid cells in atopic dermatitis. J Exp Med. 2013;210(13):2939–50.
   PubMed Web of Science ®Google Scholar
• Imai Y, Yasuda K, Sakaguchi Y, et al. Skin-specific expression of IL-33 activates group 2 innate lymphoid cells and elicits atopic dermatitis-like inflammation in mice. Proc Natl Acad Sci, USA. 2013;110(34):13921–13926. doi: 10.1073/pnas.1307321110
   PubMed Web of Science ®Google Scholar
• Imai Y. ILC2s in skin disorders. Allergol Int. 2023;72(2):201–206. doi: 10.1016/j.alit.2023.01.002
   PubMed Web of Science ®Google Scholar
• Noda S, Suárez- FariñFariñAs M, Ungar B, et al. The Asian atopic dermatitis phenotype combines features of atopic dermatitis and psoriasis with increased TH17 polarization. J Allergy Clin Immunol. 2015;136(5):1254–1264. doi: 10.1016/j.jaci.2015.08.015
   PubMed Web of Science ®Google Scholar
• Czarnowicki T, He H, Canter T, et al. Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. J Allergy Clin Immunol. 2020;145(1):215–228. doi: 10.1016/j.jaci.2019.09.031
   PubMed Web of Science ®Google Scholar
• Suárez- FariñFariñAs M, Dhingra N, Gittler J, et al. Intrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis. J Allergy Clin Immunol. 2013;132(2):361–370. doi: 10.1016/j.jaci.2013.04.046
   PubMed Web of Science ®Google Scholar
• Tokura Y, Hayano S. Subtypes of atopic dermatitis: from phenotype to endotype. Allergol Int. 2022;71(1):14–24. doi: 10.1016/j.alit.2021.07.003
   PubMed Web of Science ®Google Scholar
• Gutowska-Owsiak D, Schaupp AL, Salimi M, et al. IL-17 downregulates filaggrin and affects keratinocyte expression of genes associated with cellular adhesion. Exp Dermatol. 2012;21(2):104–110. doi: 10.1111/j.1600-0625.2011.01412.x
   PubMed Web of Science ®Google Scholar
• Ungar B, Pavel AB, Li R, et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis. J Allergy Clin Immunol. 2021;147(1):394–397. doi: 10.1016/j.jaci.2020.04.055
   PubMed Web of Science ®Google Scholar
• Khattri S, Brunner PM, Garcet S, et al. Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017;26(1):28–35. doi: 10.1111/exd.13112
   PubMed Web of Science ®Google Scholar
• Saeki H, Kabashima K, Tokura Y, et al. Efficacy and safety of ustekinumab in Japanese patients with severe atopic dermatitis: a randomized, double-blind, placebo-controlled, phase II study. Br J Dermatol. 2017;177(2):419–427. doi: 10.1111/bjd.15493
   PubMed Web of Science ®Google Scholar
• Tyring SK, Rich P, Tada Y, et al. Risankizumab in patients with moderate-to-severe atopic dermatitis: a phase 2, randomized, double-blind, placebo-controlled study. Dermatol Ther (Heidelb). 2023;13(2):595–608. doi: 10.1007/s13555-022-00876-x
   PubMed Web of Science ®Google Scholar
• Sedimbi SK, Hägglöf T, Karlsson MCI. IL-18 in inflammatory and autoimmune disease. Cell Mol Life Sci. 2013;70(24):4795–4808. doi: 10.1007/s00018-013-1425-y
   PubMed Web of Science ®Google Scholar
• Konishi H, Tsutsui H, Murakami T, et al. IL-18 contributes to the spontaneous development of atopic dermatitis-like inflammatory skin lesion independently of IgE/stat6 under specific pathogen-free conditions. Proc Natl Acad Sci, USA. 2002;99(17):11340–11345. doi: 10.1073/pnas.152337799
   PubMed Web of Science ®Google Scholar
• Chen JL, Niu XL, Gao YL, et al. IL‑18 knockout alleviates atopic dermatitis‑like skin lesions induced by MC903 in a mouse model. Int J Mol Med. 2020;46(2):880–888. doi: 10.3892/ijmm.2020.4630
   PubMed Web of Science ®Google Scholar
• Inoue Y, Aihara M, Kirino M, et al. Interleukin-18 is elevated in the horny layer in patients with atopic dermatitis and is associated with Staphylococcus aureus colonization. Br J Dermatol. 2011;164(3):560–7.
   PubMed Web of Science ®Google Scholar
• Simpson EL, Bieber T, Guttman-Yassky E, et al. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med. 2016;375(24):2335–2348. doi: 10.1056/NEJMoa1610020
   PubMed Web of Science ®Google Scholar
• Thaçi D, L. Simpson E, Deleuran M, et al. Efficacy and safety of dupilumab monotherapy in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). J Dermatol Sci. 2019;94(2):266–75.
   PubMed Web of Science ®Google Scholar
• Blauvelt A, de Bruin-Weller M, Gooderham M, et al. Long-term management of moderate-to-severe 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):2287–2303. doi: 10.1016/S0140-6736(17)31191-1
   PubMed Web of Science ®Google Scholar
• de Bruin-Weller M, Thaçi D, Smith CH, et al. Dupilumab with concomitant topical corticosteroid treatment in adults with atopic dermatitis with an inadequate response or intolerance to ciclosporin A or when this treatment is medically inadvisable: a placebo-controlled, randomized phase III clinical trial (LIBERTY AD CAFÉ). Br J Dermatol. 2018;178(5):1083–101.
   PubMed Web of Science ®Google Scholar
• Wollenberg A, Beck LA, Blauvelt A, 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):1120–1135. doi: 10.1111/bjd.18434
   PubMed Web of Science ®Google Scholar
• Worm M, Simpson EL, Thaçi D, et al.. Efficacy and Safety of Multiple Dupilumab Dose Regimens after Initial Successful Treatment in Patients with Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020;156(2):131–143. doi: 10.1001/jamadermatol.2019.3617
   PubMed Web of Science ®Google Scholar
• Beck LA, Deleuran M, Bissonnette R, et al. Dupilumab provides acceptable safety and sustained efficacy for up to 4 years in an Open-Label Study of Adults with moderate-to-severe atopic dermatitis. Am J Clin Dermatol. 2022;23(3):393–408. doi: 10.1007/s40257-022-00685-0
   PubMed Web of Science ®Google Scholar
• Paller AS, Siegfried EC, Thaçi D, et al. Efficacy and safety of dupilumab with concomitant topical corticosteroids in children 6 to 11 years old with severe atopic dermatitis: a randomized, double-blinded, placebo-controlled phase 3 trial. J Am Acad Dermatol. 2020;83(5):1282–1293. doi: 10.1016/j.jaad.2020.06.054
   PubMed Web of Science ®Google Scholar
• Simpson EL, Paller AS, Siegfried EC, et al.. Efficacy and Safety of Dupilumab in Adolescents with Uncontrolled Moderate to Severe Atopic Dermatitis: A Phase 3 Randomized Clinical Trial. JAMA Dermatol. 2020;156(1):44–56. doi: 10.1001/jamadermatol.2019.3336
   PubMed Web of Science ®Google Scholar
• Paller AS, Beck LA, Blauvelt A, et al. Infections in children and adolescents treated with dupilumab in pediatric clinical trials for atopic dermatitis—A pooled analysis of trial data. Pediatr Dermatol. 2022;39(2):187–196. doi: 10.1111/pde.14909
   PubMed Web of Science ®Google Scholar
• Paller AS, Paller AS, Simpson EL, 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. Lancet (London, England). 2022;400(10356):908–19.
   Google Scholar
• Martinez-Cabriales S, Marcoux D, Liy-Wong C, et al. Multicenter Canadian case series of pediatric patients less than 12 years of age with moderate-to-severe atopic dermatitis treated with dupilumab. Pediatr Dermatol. 2023. doi: 10.1111/pde.15418. Online ahead of print.
   PubMed Web of Science ®Google Scholar
• Armario-Hita JC, Pereyra-Rodriguez J, Silvestre JF, et al. Treatment of moderate-to-severe atopic dermatitis with dupilumab in real clinical practice: a multicentre, retrospective case series. Br J Dermatol. 2019;181(5):1072–1074. doi: 10.1111/bjd.18041
   PubMed Web of Science ®Google Scholar
• Napolitano M, Fabbrocini G, Potestio L, et al. A 24-weeks real-world experience of dupilumab in adolescents with moderate-to-severe atopic dermatitis. Dermatol Ther. 2022;35(8):e15588. doi: 10.1111/dth.15588
   PubMed Web of Science ®Google Scholar
• Torres T, Paiva-Lopes MJ, Gonçalo M, et al. Dupilumab for atopic dermatitis: a real-world Portuguese multicenter retrospective study. J DermatolTreat. 2022;33(5):2554–2559. doi: 10.1080/09546634.2022.2035309
   Google Scholar
• Halling AS, Loft N, Silverberg JI, et al. Real-world evidence of dupilumab efficacy and risk of adverse events: a systematic review and meta-analysis. J Am Acad Dermatol. 2021;84(1):139–147. doi: 10.1016/j.jaad.2020.08.051
   PubMed Web of Science ®Google Scholar
• Geba GP, Li D, Xu M, et al. Attenuating the atopic march: meta-analysis of the dupilumab atopic dermatitis database for incident allergic events. J Allergy Clin Immunol. 2023;151(3):756–766. doi: 10.1016/j.jaci.2022.08.026
   PubMed Web of Science ®Google Scholar
• Wollenberg A, Blauvelt A, Guttman-Yassky E, et al. Tralokinumab for moderate-to-severe atopic dermatitis: results from two 52-week, randomized, double-blind, multicentre, placebo-controlled phase III trials (ECZTRA 1 and ECZTRA 2). Br J Dermatol. 2021;184(3):437–449. doi: 10.1111/bjd.19574
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Toth D, Bieber T, et al. Tralokinumab plus topical corticosteroids for the treatment of moderate-to-severe atopic dermatitis: results from the double-blind, randomized, multicentre, placebo-controlled phase III ECZTRA 3 trial. Br J Dermatol. 2021;184(3):450–463. doi: 10.1111/bjd.19573
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Adam DN, Zirwas M, et al. Tralokinumab plus topical corticosteroids as needed provides progressive and sustained efficacy in adults with moderate-to-severe atopic dermatitis over a 32-week period: an ECZTRA 3 Post Hoc Analysis. Am J Clin Dermatol. 2022;23(4):547–559. doi: 10.1007/s40257-022-00702-2
   PubMed Web of Science ®Google Scholar
• Gutermuth J, Pink AE, Worm M, et al. Tralokinumab plus topical corticosteroids in adults with severe atopic dermatitis and inadequate response to or intolerance of ciclosporin A: a placebo-controlled, randomized, phase III clinical trial (ECZTRA 7). Br J Dermatol. 2022;186(3):440–452. doi: 10.1111/bjd.20832
   PubMed Web of Science ®Google Scholar
• Paller AS, Flohr C, Cork M, et al.. Efficacy and Safety of Tralokinumab in Adolescents with Moderate to Severe Atopic Dermatitis: The Phase 3 ECZTRA 6 Randomized Clinical Trial. JAMA Dermatology. 2023;159(6):596–605. doi: 10.1001/jamadermatol.2023.0627
   PubMed Web of Science ®Google Scholar
• Wollenberg A, Howell MD, Guttman-Yassky E, et al. Treatment of atopic dermatitis with tralokinumab, an anti–IL-13 mAb. J Allergy Clin Immunol. 2019;143(1):135–141. doi: 10.1016/j.jaci.2018.05.029
   PubMed Web of Science ®Google Scholar
• Merola JF, Bagel J, Almgren P, et al. Tralokinumab does not impact vaccine-induced immune responses: results from a 30-week, randomized, placebo-controlled trial in adults with moderate-to-severe atopic dermatitis. J Am Acad Dermatol. 2021;85(1):71–78. doi: 10.1016/j.jaad.2021.03.032
   PubMed Web of Science ®Google Scholar
• Simpson EL, Merola JF, Silverberg JI, 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(6):888–899. doi: 10.1111/bjd.21867
   PubMed Web of Science ®Google Scholar
• Blauvelt A, Langley RG, Lacour JP, et al. Long-term 2-year safety and efficacy of tralokinumab in adults with moderate-to-severe atopic dermatitis: interim analysis of the ECZTEND open-label extension trial. J Am Acad Dermatol. 2022;87(4):815–824. doi: 10.1016/j.jaad.2022.07.019
   PubMed Web of Science ®Google Scholar
• Gargiulo L, Ibba L, Vignoli CA, et al. Tralokinumab rapidly improves subjective symptoms and quality of life in patients with moderate-to-severe atopic dermatitis: a real-life 16-week experience. J DermatolTreat. 2023;34(1):2216815. doi: 10.1080/09546634.2023.2216815
   Google Scholar
• Pezzolo E, Schena D, Gambardella A, et al. Survival, efficacy and safety of tralokinumab after 32 and 52 weeks of treatment for moderate-to-severe atopic dermatitis in adults: a multicentre real-world study. J Eur Acad Dermatol Venereol. 2024;38(1):e11–e13. doi: 10.1111/jdv.19382
   PubMedGoogle Scholar
• Ferrucci S, Barei F, Tavecchio S, et al. Assessment of patient-reported outcomes at 24 weeks of treatment with tralokinumab for atopic dermatitis: a multicentric real-life experience. J DermatolTreat. 2023;34(1):2285243. doi: 10.1080/09546634.2023.2285243
   Google Scholar
• De Greef A, Ghislain PD, Bulinckx A, et al. Real-life experience of tralokinumab for the treatment of adult patients with severe atopic dermatitis: a multicentric prospective study. Clin Drug Investig. 2023;43(4):299–306. doi: 10.1007/s40261-023-01258-7
   PubMed Web of Science ®Google Scholar
• Schlösser AR, Shareef M, Olydam J, et al. Tralokinumab treatment for patients with moderate-to-severe atopic dermatitis in daily practice. Clin Exp Dermatol. 2023;48(5):510–517. doi: 10.1093/ced/llad038
   PubMed Web of Science ®Google Scholar
• Moyle M, Cevikbas F, Harden JL, et al. Understanding the immune landscape in atopic dermatitis: the era of biologics and emerging therapeutic approaches. Exp Dermatol. 2019;28(7):756–768. doi: 10.1111/exd.13911
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Guttman-Yassky E, Thaçi D, et al. Two phase 3 trials of lebrikizumab for moderate-to-severe atopic dermatitis. N Engl J Med. 2023;388(12):1080–1091. doi: 10.1056/NEJMoa2206714
   PubMed Web of Science ®Google Scholar
• Blauvelt A, Thyssen JP, Guttman-Yassky E, et al. Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials. Br J Dermatol. 2023;188(6):740–748. doi: 10.1093/bjd/ljad022
   PubMed Web of Science ®Google Scholar
• Simpson EL, Gooderham M, Wollenberg A, 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 Dermatology. 2023;159(2):182–191. doi: 10.1001/jamadermatol.2022.5534
   PubMed Web of Science ®Google Scholar
• Stein Gold L, Thaçi D, Thyssen JP, et al. Safety of Lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis: an integrated analysis of eight clinical trials. Am J Clin Dermatol. 2023;24(4):595–607. doi: 10.1007/s40257-023-00792-6
   PubMed Web of Science ®Google Scholar
• Kabashima K, Matsumura T, Komazaki H, et al. Trial of Nemolizumab and topical agents for atopic dermatitis with pruritus. N Engl J Med. 2020;383(2):141–150. doi: 10.1056/NEJMoa1917006
   PubMed Web of Science ®Google Scholar
• Kabashima K, Matsumura T, Komazaki H, et al. Nemolizumab plus topical agents in patients with atopic dermatitis (AD) and moderate-to-severe pruritus provide improvement in pruritus and signs of AD for up to 68 weeks: results from two phase III, long-term studies. Br J Dermatol. 2022;186(4):642–651. doi: 10.1111/bjd.20873
   PubMed Web of Science ®Google Scholar
• Kabashima K, Matsumura T, Komazaki H, et al. Nemolizumab improves patient-reported symptoms of atopic dermatitis with pruritus: Post Hoc Analysis of a Japanese phase III randomized controlled trial. Dermatol Ther (Heidelb). 2023;13(4):997–1011. doi: 10.1007/s13555-023-00901-7
   PubMed Web of Science ®Google Scholar
• Igarashi A, Katsunuma T, Matsumura T, et al. Efficacy and safety of nemolizumab in paediatric patients aged 6-12 years with atopic dermatitis with moderate-to-severe pruritus: Results from a phase III, randomised, double-blind, placebo-controlled, multicentre study. Br J Dermatol. 2023;190(1):20–8.
   PubMed Web of Science ®Google Scholar
• Guttman-Yassky E, Brunner PM, Neumann AU, 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):872–81.e6. doi: 10.1016/j.jaad.2018.01.016
   PubMed Web of Science ®Google Scholar
• Morita A, Strober B, Burden AD, et al. Efficacy and safety of subcutaneous spesolimab for the prevention of generalised pustular psoriasis flares (Effisayil 2): an international, multicentre, randomised, placebo-controlled trial. Lancet (London, England). 2023;402(10412):1541–51.
   Google Scholar
• Bissonnette R, Abramovits W, Saint-Cyr Proulx É, et al. Spesolimab, an anti-interleukin-36 receptor antibody, in patients with moderate-to-severe atopic dermatitis: results from a multicentre, randomized, double-blind, placebo-controlled, phase IIa study. J Eur Acad Dermatol Venereol. 2023;37(3):549–557. doi: 10.1111/jdv.18727
   PubMed Web of Science ®Google Scholar
• Chen YL, Gutowska-Owsiak D, Hardman CS, et al. Proof-of-concept clinical trial of etokimab shows a key role for IL-33 in atopic dermatitis pathogenesis. Sci Transl Med. 2019;11(515):eaax2945. doi: 10.1126/scitranslmed.aax2945
   PubMed Web of Science ®Google Scholar
• Zhao Y, Zhang J, Yang B, et al. Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis: A multicenter, randomized, double-blind, placebo-controlled phase 2b trial. Chin Med J (Engl). 2023. doi: 10.1097/CM9.0000000000002747. Online ahead of print.
   Google Scholar
• Wang J, White J, Sansone KJ, et al. Rademikibart (CBP-201), a next-generation monoclonal antibody targeting human IL-4Rα: two phase I randomized trials, in healthy individuals and patients with atopic dermatitis. Clin Transl Sci. 2023;16(12):2614–2627. doi: 10.1111/cts.13656
   PubMed Web of Science ®Google Scholar
• A Dose Finding Study to Investigate the Safety and Effectiveness of GSK1070806 in Adult Participants With Moderate to Severe Atopic Dermatitis. ClinicalTrials.gov. Accessed March 2, 2024. https://clinicaltrials.gov/study/NCT05999799
   Google Scholar
• A Two-Part. Phase 1, Single-Dose Study of IL-31 mAb (Anti-Interleukin 31 Monoclonal Antibody); in Healthy Subjects and Adults With Atopic Dermatitis. ClinicalTrials.gov. Accessed March 2, 2024. https://clinicaltrials.gov/study/NCT01614756
   Google Scholar
• Picone V, Vallone Y, Patruno C, et al. An overview of new and emerging antibody therapies for moderate-severe atopic dermatitis inadults. Expert Rev Clin Pharmacol. 2023;16(12):1239–1248 10.1080/17512433.2023.2292615
   PubMed Web of Science ®Google Scholar
• Baffa ME, Pipitò C, Montefusco F, et al. Tralokinumab efficacy in a case of dupilumab-resistant severe atopic dermatitis complicated by eczema herpeticum. J Eur Acad Dermatol Venereol. 2023;37(8):e1028–e1030. doi: 10.1111/jdv.19091. Online ahead of print.
   PubMed Web of Science ®Google Scholar
• Quattrini L, Caldarola G, Falco GM,et al. Successful treatment with tralokinumab in patients with atopic dermatitis and dupilumab-induced psoriasis. J Eur Acad Dermatol Venereol. 2023;37(12):e1432–e1434.
   PubMed Web of Science ®Google Scholar
• Licata G, Gambardella A, Tancredi V, et al. Face atopic dermatitis resistant to dupilumab: a case series of three patients successfully treated with upadacitinib. J Eur Acad Dermatol Venereol. 2022;36(2):e150–e152. doi: 10.1111/jdv.17705
   PubMed Web of Science ®Google Scholar
• Achten R, Dekkers C, Bakker D, et al. Switching from dupilumab to tralokinumab in atopic dermatitis patients with ocular surface disease: preliminary case series. Clin Exp Allergy. 2023;53(5):586–589. doi: 10.1111/cea.14305
   PubMed Web of Science ®Google Scholar
• Blauvelt A, Teixeira HD, Simpson EL, et al.. Efficacy and Safety of Upadacitinib vs Dupilumab in Adults With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA dermatology. 2021;157(9):1047–1055. doi: 10.1001/jamadermatol.2021.3023
   PubMed Web of Science ®Google Scholar
• Bieber T, Simpson EL, Silverberg JI, et al. Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis. N Engl J Med. 2021 Mar;384(12):1101–1112.10.1056/NEJMoa2019380
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Thyssen JP, Fahrbach K, et al. Comparative efficacy and safety of systemic therapies used in moderate-to-severe atopic dermatitis: a systematic literature review and network meta-analysis. J Eur Acad Dermatol Venereol. 2021;35(9):1797–1810. doi: 10.1111/jdv.17351.
   PubMed Web of Science ®Google Scholar
• Silverberg JI, Jacob HCH. Comparative Efficacy of Targeted Systemic Therapies for Moderate to Severe Atopic Dermatitis without Topical Corticosteroids : Systematic Review and Network Meta-analysis. Dermatol Ther (Heidelb). 2022;1181–96.
   PubMed Web of Science ®Google Scholar
• Drucker AM, Morra DE, Prieto-Merino D, et al.. Systemic Immunomodulatory Treatments for Atopic Dermatitis: Update of a Living Systematic Review and Network Meta-analysis. JAMA dermatology. 2022;158(5):523–532. doi: 10.1001/jamadermatol.2022.0455
   PubMed Web of Science ®Google Scholar
• Drucker AM, Lam M, Elsawi R, et al. Comparing binary efficacy outcomes for systemic immunomodulatory treatments for atopic dermatitis in a living systematic review and network meta-analysis. Br J Dermatol. 2023:ljad393.
   Google Scholar
• Reich K, Thyssen JP, Blauvelt A, et al.. Comparing how well abrocitinib and dupilumab treat atopic dermatitis signs and symptoms: a plain language summary. Immunotherapy. 2023;15(13):975–980. doi: 10.2217/imt-2022-0306
   PubMed Web of Science ®Google Scholar
• Bieber T. Disease modification in inflammatory skin disorders: opportunities and challenges. Nat Rev Drug Discov. 2023;22(8):662–680. doi: 10.1038/s41573-023-00735-0
   PubMed Web of Science ®Google Scholar
• Shi VY, Bhutani T, Fonacier L, et al. Phase 3 efficacy and safety of abrocitinib in adults with moderate-to-severe atopic dermatitis after switching from dupilumab (JADE EXTEND). J Am Acad Dermatol. 2022;87(2):351–358. doi: 10.1016/j.jaad.2022.04.009
   PubMed Web of Science ®Google Scholar
• Cork MJ, Thaçi D, Eichenfield LF, et al. Dupilumab Safety and Efficacy in a Phase III Open-Label Extension Trial in Children 6-11 Years of Age with Severe Atopic Dermatitis. Dermatol Ther (Heidelb). 2023;13(11):2697–719.
   PubMedGoogle Scholar
• Guttman-Yassky E, Simpson EL, Reich K, et al. An anti-OX40 antibody to treat moderate-to-severe atopic dermatitis: a multicentre, double-blind, placebo-controlled phase 2b study. Lancet (London, England). 2023;401(10372):204–14.
   Google Scholar
• Weidinger S, Bieber T, Cork MJ, et al. Safety and efficacy of amlitelimab, a fully human nondepleting, noncytotoxic anti-OX40 ligand monoclonal antibody, in atopic dermatitis: results of a phase IIa randomized placebo-controlled trial. Br J Dermatol. 2023;189(5):531–539. doi: 10.1093/bjd/ljad240
   PubMed Web of Science ®Google Scholar