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Biologics for Allergic Dermatologic Diseases

  • Allergic Skin Diseases (L Fonacier and A Wollenberg, Section Editors)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Atopic dermatitis (AD), chronic spontaneous urticaria (CSU), and allergic contact dermatitis (ACD) represent three important allergic dermatoses with many unmet therapeutic needs. The development of biologic agents has opened the door to both new treatment options and improved understanding of the underlying pathophysiology, both shared and unique for these entities. With several FDA-approved medications available and many more in development, the biologic revolution has begun for allergic dermatoses.

Recent Findings

This is a narrative review on the current state of pathomechanisms and appropriately targeted biologic agents for these three common allergic skin conditions. The importance of Th2 inflammation and the effect of inflammatory cytokines on the skin barrier may help explain the impressive efficacy of biologic agents, while maintaining relative safety. While some of the biologic agents show efficacy across multiple allergic dermatoses, more often it seems these more targeted pathways show accordingly precise efficacy. However, in each disease, multiple agents hold promise, and may be differentiated by safety and adverse effect profile rather than simply by efficacy.

Summary

New understanding of the pathogenesis of the allergic dermatoses has ushered in a new era of biologic therapies. Competing mechanisms and molecules will continue to be developed and vetted in trials with hopes of continuously refined precision therapies with optimized safety and efficacy profiles.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. • Chiesa Fuxench ZC, Block JK, Boguniewicz M, Boyle J, Fonacier L, Gelfand JM, et al. Atopic dermatitis in America study: a cross-sectional study examining the prevalence and disease burden of atopic dermatitis in the US adult population. J Invest Dermatol. 2019;139:583–90 Very up to date disease prevalence and burden study of atopic dermatitis.

    Article  CAS  PubMed  Google Scholar 

  2. Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema prevalence in the United States: data from the 2003 National Survey of Children’s Health. J Invest Dermatol. 2011;131:67–73.

    Article  CAS  PubMed  Google Scholar 

  3. Rønnstad ATM, Halling-Overgaard A-S, Hamann CR, Skov L, Egeberg A, Thyssen JP. Association of atopic dermatitis with depression, anxiety, and suicidal ideation in children and adults: a systematic review and meta-analysis. J Am Acad Dermatol. 2018;79:448–56.e30.

    Article  PubMed  Google Scholar 

  4. Bickers DR, Lim HW, Margolis D, Weinstock MA, Goodman C, Faulkner E, et al. The burden of skin diseases: 2004 a joint project of the American Academy of Dermatology Association and the Society for Investigative Dermatology. J Am Acad Dermatol. 2006;55:490–500.

    Article  PubMed  Google Scholar 

  5. David Boothe W, Tarbox JA, Tarbox MB. Atopic dermatitis: pathophysiology. In: Fortson EA, Feldman SR, Strowd LC, editors. Management of atopic dermatitis: methods and challenges: Springer International Publishing. p. 21–37.

  6. Peng W, Novak N. Pathogenesis of atopic dermatitis. Clin Exp Allergy. 2015;45:566–74.

    Article  CAS  PubMed  Google Scholar 

  7. Furue M, Chiba T, Tsuji G, Ulzii D, Kido-Nakahara M, Nakahara T, et al. Atopic dermatitis: immune deviation, barrier dysfunction, IgE autoreactivity and new therapies. Allergol Int. 2017;66:398–403.

    Article  CAS  PubMed  Google Scholar 

  8. Furue M, Tsuji G, Mitoma C, Nakahara T, Chiba T, Morino-Koga S, et al. Gene regulation of filaggrin and other skin barrier proteins via aryl hydrocarbon receptor. J Dermatol Sci. 2015;80:83–8.

    Article  CAS  PubMed  Google Scholar 

  9. Lio PA. Atopic dermatitis and food allergies: true, true and related? Arch Dis Child Educ Pract Ed. 2007;92(2):ep56–60.

    Article  PubMed  Google Scholar 

  10. Krasteva M, Kehren J, Horand F, Akiba H, Choquet G, Ducluzeau MT, et al. Dual role of dendritic cells in the induction and down-regulation of antigen-specific cutaneous inflammation. J Immunol. 1998;160:1181–90.

    CAS  PubMed  Google Scholar 

  11. • Fonacier LS, Aquino MR. The role of contact allergy in atopic dermatitis. Immunol Allergy Clin North Am. 2010;30:337–50 An exploration of the connections between contact allergy and atopic dermatitis.

    Article  PubMed  Google Scholar 

  12. Tan C-H, Rasool S, Johnston GA. Contact dermatitis: allergic and irritant. Clin Dermatol. 2014;32:116–24.

    Article  PubMed  Google Scholar 

  13. Developing dermal policy based on laboratory and field studies: a new National Institute for Occupational Safety and Health (NIOSH) research program in response to the National Occupational Research Agenda (NORA) [Internet]. National Institute for Occupational Safety and Health (NIOSH). ; Available from: https://www.cdc.gov/niosh/docs/2000-142/pdfs/2000-142.pdf

  14. Cashman MW, Reutemann PA, Ehrlich A. Contact dermatitis in the United States: epidemiology, economic impact, and workplace prevention. Dermatol Clin. 2012;30:87–98 viii.

    Article  CAS  PubMed  Google Scholar 

  15. Zuberbier T, Aberer W, Asero R, Abdul Latiff AH, Baker D, Ballmer-Weber B, et al. The EAACI/GA2LEN/EDF/WAO guideline for the definition, classification, diagnosis and management of urticaria. Allergy. 2018;73:1393–414.

    Article  CAS  PubMed  Google Scholar 

  16. • Kolkhir P, Church MK, Weller K, Metz M, Schmetzer O, Maurer M. Autoimmune chronic spontaneous urticaria: What we know and what we do not know. J Allergy Clin Immunol. 2017;139:1772–81.e1 Detailed review of chronic spontaneous urticaria.

    Article  CAS  PubMed  Google Scholar 

  17. Kaplan AP, Horáková Z, Katz SI. Assessment of tissue fluid histamine levels in patients with urticaria. J Allergy Clin Immunol. 1978;61:350–4.

    Article  CAS  PubMed  Google Scholar 

  18. Pasaoglu G, Bavbek S, Tugcu H, Abadoglu O, Misirligil Z. Psychological status of patients with chronic urticaria. J Dermatol. 2006;33:765–71.

    Article  PubMed  Google Scholar 

  19. Schneider L, Tilles S, Lio P, Boguniewicz M, Beck L, LeBovidge J, et al. Atopic dermatitis: a practice parameter update 2012. J Allergy Clin Immunol. 2013;131:295–9.e1–27.

    Article  PubMed  Google Scholar 

  20. Wilkin JK, DuComb D, Castrow FF. Scarification treatment of granuloma annulare. Arch Dermatol. jamanetwork.com. 1982;118:68–9.

    Article  CAS  PubMed  Google Scholar 

  21. Lawrence MG, Steinke JW, Borish L. Cytokine-targeting biologics for allergic diseases. Ann Allergy Asthma Immunol. 2018;120:376–81.

    Article  CAS  PubMed  Google Scholar 

  22. Rubbert-Roth A, Atzeni F, Masala IF, Caporali R, Montecucco C, Sarzi-Puttini P. TNF inhibitors in rheumatoid arthritis and spondyloarthritis: Are they the same? Autoimmun Rev. 2018;17:24–8.

    Article  CAS  PubMed  Google Scholar 

  23. Lonberg N. Fully human antibodies from transgenic mouse and phage display platforms. Curr Opin Immunol. 2008;20:450–9.

    Article  CAS  PubMed  Google Scholar 

  24. Hwang WYK, Foote J. Immunogenicity of engineered antibodies. Methods. 2005;36:3–10.

    Article  CAS  PubMed  Google Scholar 

  25. Galli SJ, Tsai M. IgE and mast cells in allergic disease. Nat Med. nature.com. 2012;18:693–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Guttman-Yassky E, Dhingra N, Leung DYM. New era of biologic therapeutics in atopic dermatitis. Expert Opin Biol Ther. 2013;13:549–61.

    Article  CAS  PubMed  Google Scholar 

  27. Wang H-H, Li Y-C, Huang Y-C. Efficacy of omalizumab in patients with atopic dermatitis: A systematic review and meta-analysis. J Allergy Clin Immunol. search.proquest.com. 2016;138:1719–22.e1.

    Article  CAS  PubMed  Google Scholar 

  28. Krathen RA, Hsu S. Failure of omalizumab for treatment of severe adult atopic dermatitis. J Am Acad Dermatol. Elsevier. 2005;53:338–40.

    Article  Google Scholar 

  29. Iyengar SR, Hoyte EG, Loza A, Bonaccorso S, Chiang D, Umetsu DT, et al. Immunologic effects of omalizumab in children with severe refractory atopic dermatitis: a randomized, placebo-controlled clinical trial. Int Arch Allergy Immunol. karger.com. 2013;162:89–93.

    Article  CAS  PubMed  Google Scholar 

  30. Lane JE, Cheyney JM, Lane TN, Kent DE, Cohen DJ. Treatment of recalcitrant atopic dermatitis with omalizumab. J Am Acad Dermatol. Elsevier. 2006;54:68–72.

    Article  Google Scholar 

  31. Mur Gimeno P, Martín Iglesias A, Lombardero Vega M, Bautista Martínez P, Ventura LP. Occupational wheat contact dermatitis and treatment with omalizumab. J Investig Allergol Clin Immunol. 2013;23:287–8.

    CAS  PubMed  Google Scholar 

  32. • Kolkhir P, Altrichter S, Munoz M, Hawro T, Maurer M. New treatments for chronic urticaria. Ann Allergy Asthma Immunol. 2020;124:2–12 Overview of new therapies for urticaria.

    Article  CAS  PubMed  Google Scholar 

  33. Arm JP, Bottoli I, Skerjanec A, Floch D, Groenewegen A, Maahs S, et al. Pharmacokinetics, pharmacodynamics and safety of QGE031 (ligelizumab), a novel high-affinity anti-IgE antibody, in atopic subjects. Clin Exp Allergy. 2014;44:1371–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Maurer M, Giménez-Arnau AM, Sussman G, Metz M, Baker DR, Bauer A, et al. Ligelizumab for Chronic Spontaneous Urticaria. N Engl J Med. 2019;381:1321–32.

    Article  CAS  PubMed  Google Scholar 

  35. Simon D, Wittwer J, Kostylina G, Buettiker U, Simon H-U, Yawalkar N. Alefacept (lymphocyte function-associated molecule 3/IgG fusion protein) treatment for atopic eczema. J Allergy Clin Immunol. 2008;122:423–4.

    Article  CAS  PubMed  Google Scholar 

  36. Hassan AS, Kaelin U, Braathen LR, Yawalkar N. Clinical and immunopathologic findings during treatment of recalcitrant atopic eczema with efalizumab. J Am Acad Dermatol. 2007;56:217–21.

    Article  PubMed  Google Scholar 

  37. Mauri C. Regulation of immunity and autoimmunity by B cells. Curr Opin Immunol. 2010;22:761–7.

    Article  CAS  PubMed  Google Scholar 

  38. Simon D, Hösli S, Kostylina G, Yawalkar N, Simon H-U. Anti-CD20 (rituximab) treatment improves atopic eczema. J Allergy Clin Immunol. 2008;121:122–8.

    Article  CAS  PubMed  Google Scholar 

  39. Combalia A, Losno RA. Prieto-González S, Mascaró JM. Rituximab in refractory chronic spontaneous urticaria: an encouraging therapeutic approach. Skin Pharmacol Physiol. 2018;31.

  40. Czarnowicki T, Krueger JG, Guttman-Yassky E. Skin barrier and immune dysregulation in atopic dermatitis: an evolving story with important clinical implications. J Allergy Clin Immunol Pract. 2014;2:371–9 quiz 380–1.

    Article  PubMed  Google Scholar 

  41. Brunner PM, Guttman-Yassky E, Leung DYM. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139:S65–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis--part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011;127:1420–32.

    Article  CAS  PubMed  Google Scholar 

  43. Spergel JM, Mizoguchi E, Oettgen H, Bhan AK, Geha RS. Roles of TH1 and TH2 cytokines in a murine model of allergic dermatitis. J Clin Invest. 1999;103:1103–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Leckie MJ, ten Brinke A, Khan J, Diamant Z, O’Connor BJ, Walls CM, et al. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000;356:2144–8.

    Article  CAS  PubMed  Google Scholar 

  45. Oldhoff JM, Darsow U, Werfel T, Katzer K, Wulf A, Laifaoui J, et al. Anti-IL-5 recombinant humanized monoclonal antibody (mepolizumab) for the treatment of atopic dermatitis. Allergy. 2005;60:693–6.

    Article  CAS  PubMed  Google Scholar 

  46. Kang EG, Narayana PK, Pouliquen IJ, Lopez MC, Ferreira-Cornwell MC, Getsy JA. Efficacy and safety of mepolizumab administered subcutaneously for moderate to severe atopic dermatitis. Allergy [Internet]. 2019; Available from: https://doi.org/10.1111/all.14050.

  47. Corren J. Anti-interleukin-5 antibody therapy in asthma and allergies. Curr Opin Allergy Clin Immunol. 2011;11:565–70.

    Article  CAS  PubMed  Google Scholar 

  48. Magerl M, Terhorst D, Metz M, Altrichter S, Zuberbier T, Maurer M, et al. Benefit of mepolizumab treatment in a patient with chronic spontaneous urticaria. J Dtsch Dermatol Ges. 2018;16:477–8.

    Article  PubMed  Google Scholar 

  49. Maurer M, Altrichter S, Metz M, Zuberbier T, Church MK, Bergmann K-C. Benefit from reslizumab treatment in a patient with chronic spontaneous urticaria and cold urticaria. J Eur Acad Dermatol Venereol. 2018;32:e112–3.

    Article  CAS  PubMed  Google Scholar 

  50. Bergmann KC, Altrichter S, Maurer M. Benefit of benralizumab treatment in a patient with chronic symptomatic dermographism. J Eur Acad Dermatol Venereol. 2019;33:e413–5.

    Article  CAS  PubMed  Google Scholar 

  51. Dillon SR, Sprecher C, Hammond A, Bilsborough J, Rosenfeld-Franklin M, Presnell SR, et al. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat Immunol. 2004;5:752–60.

    Article  CAS  PubMed  Google Scholar 

  52. Cornelissen C, Lüscher-Firzlaff J, Baron JM, Lüscher B. Signaling by IL-31 and functional consequences. Eur J Cell Biol. 2012;91:552–66.

    Article  CAS  PubMed  Google Scholar 

  53. Sonkoly E, Muller A, Lauerma AI, Pivarcsi A, Soto H, Kemeny L, et al. IL-31: a new link between T cells and pruritus in atopic skin inflammation. J Allergy Clin Immunol. 2006;117:411–7.

    Article  CAS  PubMed  Google Scholar 

  54. Raap U, Wichmann K, Bruder M, Ständer S, Wedi B, Kapp A, et al. Correlation of IL-31 serum levels with severity of atopic dermatitis. J Allergy Clin Immunol. 2008;122:421–3.

    Article  CAS  PubMed  Google Scholar 

  55. 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;25:334–9.

    Article  CAS  PubMed  Google Scholar 

  56. Cornelissen C, Marquardt Y, Czaja K, Wenzel J, Frank J, Lüscher-Firzlaff J, et al. IL-31 regulates differentiation and filaggrin expression in human organotypic skin models. J Allergy Clin Immunol. 2012;129:426–33 433.e1–8.

    Article  CAS  PubMed  Google Scholar 

  57. Ruzicka T, Hanifin JM, Furue M, Pulka G, Mlynarczyk I, Wollenberg A, et al. Anti-interleukin-31 receptor A antibody for atopic dermatitis. N Engl J Med. 2017;376:826–35.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  59. • Ständer S, Yosipovitch G, Legat FJ, Lacour J-P, Paul C, Narbutt J, et al. Trial of nemolizumab in moderate-to-severe prurigo Nodularis. N Engl J Med. 2020;382:706–16 Study of nemolizumab for prurigo nodularis.

    Article  PubMed  Google Scholar 

  60. Petronelli M. Breakthrough therapy designation granted to nemolizumab for pruritus. Dermatology Times [Internet]. 2020;41. Available from: https://www.dermatologytimes.com/biologics/breakthrough-therapy-designation-granted-nemolizumab-pruritus

  61. Raap U, Wieczorek D, Gehring M, Pauls I, Ständer S, Kapp A, et al. Increased levels of serum IL-31 in chronic spontaneous urticaria. Exp Dermatol. Wiley Online Library. 2010;19:464–6.

    CAS  Google Scholar 

  62. Neis MM, Peters B, Dreuw A, Wenzel J, Bieber T, Mauch C, 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. Elsevier. 2006;118:930–7.

    Article  CAS  Google Scholar 

  63. 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;78:872–81.e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Lou H, Lu J, Choi EB, Oh MH, Jeong M, Barmettler S, et al. Expression of IL-22 in the skin causes Th2-biased immunity, epidermal barrier dysfunction, and pruritus via stimulating epithelial Th2 cytokines and the GRP pathway. The Journal of Immunology. American Association of Immunologists. 2017;198:2543–55.

    CAS  Google Scholar 

  65. Palmer MT, Weaver CT. Autoimmunity: increasing suspects in the CD4+ T cell lineup. Nat Immunol. 2010;11:36–40.

    Article  CAS  PubMed  Google Scholar 

  66. Fernández-Antón Martínez MC, Alfageme Roldán F, Ciudad Blanco C, Suárez FR. Ustekinumab in the treatment of severe atopic dermatitis: a preliminary report of our experience with 4 patients. Actas Dermosifiliogr. 2014;105:312–3.

    Article  PubMed  Google Scholar 

  67. 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. Br J Dermatol. 2017;177:419–27.

    Article  CAS  PubMed  Google Scholar 

  68. Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol [Internet]. 2011;2. Available from: 10.4172/2155-9899.1000110.

  69. Tazawa T, Sugiura H, Sugiura Y, Uehara M. Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res. 2004;295:459–64.

    Article  CAS  PubMed  Google Scholar 

  70. Howell MD, Kim BE, Gao P, Grant AV, Boguniewicz M, DeBenedetto A, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2009;124:R7–12.

    Article  CAS  PubMed  Google Scholar 

  71. Kim BE, Leung DYM, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008;126:332–7.

    Article  CAS  PubMed  Google Scholar 

  72. Totté JEE, van der Feltz WT, Hennekam M, van Belkum A, van Zuuren EJ, Pasmans SGMA. Prevalence and odds of Staphylococcus aureus carriage in atopic dermatitis: a systematic review and meta-analysis. Br J Dermatol. 2016;175:687–95.

    Article  PubMed  Google Scholar 

  73. Kisich KO, Carspecken CW, Fiéve S, Boguniewicz M, Leung DYM. Defective killing of Staphylococcus aureus in atopic dermatitis is associated with reduced mobilization of human beta-defensin-3. J Allergy Clin Immunol. 2008;122:62–8.

    Article  CAS  PubMed  Google Scholar 

  74. Shirakawa I, Deichmann KA, Izuhara I, Mao I, Adra CN, Hopkin JM. Atopy and asthma: genetic variants of IL-4 and IL-13 signalling. Immunol Today. 2000;21:60–4.

    Article  CAS  PubMed  Google Scholar 

  75. Gauchat JF, Henchoz S, Mazzei G, Aubry JP, Brunner T, Blasey H, et al. Induction of human IgE synthesis in B cells by mast cells and basophils. Nature. 1993;365:340–3.

    Article  CAS  PubMed  Google Scholar 

  76. Stott B, Lavender P, Lehmann S, Pennino D, Durham S, Schmidt-Weber CB. Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation. J Allergy Clin Immunol. 2013;132:446–54.e5.

    Article  CAS  PubMed  Google Scholar 

  77. Silverberg JI, Kantor R. The Role of Interleukins 4 and/or 13 in the Pathophysiology and Treatment of Atopic Dermatitis. Dermatol Clin. Elsevier Inc. 2017;35:327–34.

    Article  CAS  Google Scholar 

  78. Tanaka Y, Hamano S, Gotoh K, Murata Y, Kunisaki Y, Nishikimi A, et al. T helper type 2 differentiation and intracellular trafficking of the interleukin 4 receptor-alpha subunit controlled by the Rac activator Dock2. Nat Immunol. 2007;8:1067–75.

    Article  CAS  PubMed  Google Scholar 

  79. Kotowicz K, Callard RE, Friedrich K, Matthews DJ, Klein N. Biological activity of IL-4 and IL-13 on human endothelial cells: functional evidence that both cytokines act through the same receptor. Int Immunol. 1996;8:1915–25.

    Article  CAS  PubMed  Google Scholar 

  80. •• 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;375:2335–48 Phase 3 study results of dupilumab showing safety and efficacy data in atopic dermatitis.

    Article  CAS  PubMed  Google Scholar 

  81. Blauvelt A, de Bruin-Weller M, Gooderham M, Cather JC, Weisman J, Pariser D, 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;389:2287–303.

    Article  CAS  PubMed  Google Scholar 

  82. •• 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 [Internet]. 2019; Available from: 10.1111/bjd.18434 COMMENT: Analysis of laboratory safety of 3 Phase 3 studies of dupilumab in atopic dermatitis.

  83. Wenzel S, Castro M, Corren J, Maspero J, Wang L, Zhang B, et al. Dupilumab efficacy and safety in adults with uncontrolled persistent asthma despite use of medium-to-high-dose inhaled corticosteroids plus a long-acting β2 agonist: a randomised double-blind placebo-controlled pivotal phase 2b dose-ranging trial. Lancet. Elsevier. 2016;388:31–44.

    Article  CAS  Google Scholar 

  84. Bachert C, Mannent L, Naclerio RM, Mullol J, Ferguson BJ, Gevaert P, et al. Effect of subcutaneous dupilumab on nasal polyp burden in patients with chronic sinusitis and nasal polyposis: a randomized clinical trial. JAMA. 2016;315:469–79.

    Article  CAS  PubMed  Google Scholar 

  85. Cork MJ, Thaçi 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;182:85–96.

    Article  CAS  PubMed  Google Scholar 

  86. Thiel B, Eichenfield LF. FDA approval of Dupixent for AD in teens’ changes the game plan'. Infectious Diseases in Children. SLACK INCORPORATED. 2019;32:16–7.

    Google Scholar 

  87. Dupixent® (dupilumab) Showed Positive Topline Results in Phase 3 Trial of Children Aged 6 to 11 Years with Severe Atopic Dermatitis | Regeneron Pharmaceuticals Inc [Internet]. Regeneron Pharmaceuticals Inc. [cited 2020 Feb 16]. Available from: https://newsroom.regeneron.com/news-releases/news-release-details/dupixentr-dupilumab-showed-positive-topline-results-phase-3

  88. Nessler J. FDA grants priority review to dupilumab for Atopic Dermatitis In Children. Pharm Times. 2020 Jan;28.

  89. Safety, Pharmacokinetics and Efficacy of Dupilumab in Patients ≥6 Months to <6 Years With Severe Atopic Dermatitis (Liberty AD PRESCHOOL) [Internet]. ClinicalTrials.gov. [cited 2020 Feb 1]. Available from: https://clinicaltrials.gov/ct2/show/NCT03346434

  90. Treister AD, Lio PA. Long-term off-label dupilumab in pediatric atopic dermatitis: a case series. Pediatr Dermatol. 2019;36:85–8.

    Article  PubMed  Google Scholar 

  91. Igelman S, Kurta AO, Sheikh U, McWilliams A, Armbrecht E, Jackson Cullison SR, et al. Off-label use of dupilumab for pediatric patients with atopic dermatitis: a multicenter retrospective review. J Am Acad Dermatol. Elsevier. 2020;82:407–11.

    Article  Google Scholar 

  92. Chipalkatti N, Lee N, Zancanaro P, Dumont N, Donovan C, Rosmarin D. Dupilumab as a treatment for allergic contact dermatitis. Dermatitis. 2018;29:347–8.

    Article  CAS  PubMed  Google Scholar 

  93. Raffi J, Suresh R, Botto N, Murase JE. The impact of dupilumab on patch testing and the prevalence of comorbid allergic contact dermatitis in recalcitrant atopic dermatitis: a retrospective chart review. J Am Acad Dermatol. Elsevier. 2020;82:132–8.

    Article  CAS  Google Scholar 

  94. Raffi J, Botto N. Patch testing and allergen-specific inhibition in a patient taking dupilumab. JAMA Dermatol. jamanetwork.com. 2019;155:120–1.

    Article  PubMed  Google Scholar 

  95. Lee JK, Simpson RS. Dupilumab as a novel therapy for difficult to treat chronic spontaneous urticaria. J Allergy Clin Immunol Pract. 2019;7:1659–61.e1.

    Article  PubMed  Google Scholar 

  96. Khattri S, Shemer A, Rozenblit M, Dhingra N, Czarnowicki T, Finney R, et al. Cyclosporine in patients with atopic dermatitis modulates activated inflammatory pathways and reverses epidermal pathology. J Allergy Clin Immunol. 2014;133:1626–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Corren J, Lemanske RF, Hanania NA, Korenblat PE, Parsey MV, Arron JR, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088–98.

    Article  CAS  PubMed  Google Scholar 

  98. •• Simpson EL, Flohr C, Eichenfield LF, Bieber T, Sofen H, Taïeb A, et al. Efficacy and safety of lebrikizumab (an anti-IL-13 monoclonal antibody) in adults with moderate-to-severe atopic dermatitis inadequately controlled by topical corticosteroids: A randomized, placebo-controlled phase II trial (TREBLE). J Am Acad Dermatol. 2018;78:863–71.e11 Phase 2 study results of lebrikizumab showing safety and efficacy data.

    Article  CAS  PubMed  Google Scholar 

  99. Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Birrell C, Kell C, et al. A phase 2b dose-ranging efficacy and safety study of tralokinumab in adult patients with moderate to severe atopic dermatitis (AD). J Am Acad Dermatol. Ludwig-Maximilians-Universität München. 2017:AB20.

  100. •• Wollenberg A, Howell MD, Guttman-Yassky E, Silverberg JI, Kell C, Ranade K, et al. Treatment of atopic dermatitis with tralokinumab, an anti–IL-13 mAb. J Allergy Clin Immunol. Elsevier. 2019;143:135–41 Phase 2b study results of tralokinumab showing safety and efficacy data.

    Article  CAS  Google Scholar 

  101. Liu Y-J. Thymic stromal lymphopoietin and OX40 ligand pathway in the initiation of dendritic cell–mediated allergic inflammation. J Allergy Clin Immunol. 2007;120:238–44.

    Article  CAS  PubMed  Google Scholar 

  102. Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol. 2002;3:673–80.

    Article  CAS  PubMed  Google Scholar 

  103. 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;80:1013–21.

    Article  CAS  PubMed  Google Scholar 

  104. Kay AB, Clark P, Maurer M, Ying S. Elevations in T-helper-2-initiating cytokines (interleukin-33, interleukin-25 and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous (’idiopathic') urticaria. Br J Dermatol. 2015;172:1294–302.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Northwestern University Feinberg School of Medicine, 363 W. Erie Street, Suite 350, Chicago, IL, 60616, USA

    Sara N. Bilimoria & Peter A. Lio

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  1. Sara N. Bilimoria
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  2. Peter A. Lio
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Correspondence to Peter A. Lio.

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Conflict of Interest

Dr. Bilimoria reports a grant from the National Eczema Association during the conduct of the study. Dr. Lio reports personal fees from UCB, personal fees from Dermavant, grants and personal fees from Regeneron/Sanofi Genzyme, personal fees from Dermira, personal fees from Pfizer, personal fees from LEO Pharmaceuticals, grants and personal fees from AbbVie, personal fees from Kiniksa, personal fees from Eli Lilly, during the conduct of the study; personal fees from La Roche Posay/L’Oreal, personal fees from Pierre-Fabre, personal fees from Johnson & Johnson, personal fees from Unilever, personal fees from Menlo Therapeutics, personal fees from Theraplex, personal fees from IntraDerm, personal fees from Exeltis, grants and personal fees from AOBiome, personal fees from Realm Therapetuics, personal fees and other from Franklin Bioscience/Altus Labs, personal fees from Verrica, personal fees from TopMD, personal fees from Arbonne, personal fees from Burt’s Bees, grants from the National Eczema Association, outside the submitted work. In addition, Dr. Lio has a patent Theraplex Product with royalties paid and Board member and Scientific Advisory Committee Member of the National Eczema Association.

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This article is part of the Topical Collection on Allergic Skin Diseases

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Bilimoria, S.N., Lio, P.A. Biologics for Allergic Dermatologic Diseases. Curr Allergy Asthma Rep 20, 35 (2020). https://doi.org/10.1007/s11882-020-00923-7

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