Table Info

Table 4.

AIT studies in AD

Study type	Allergen	Treatment duration	Number of patients enrolled	Complementary medication	Route	Global endpoints achieved	Adverse reactions reported	References
Open-label, controlled, randomized trial	HDM	12 months	60	Moisturisers, topical and systemic drugs	SL	Significant increase of allergen-specific Ig4	Oropharyngeal itching, localized lip swelling	[170]
Randomized controlled trial	HDM	36 months	440	Topical glucocorticoids, skin moisturizers, oral antihistamines	SL	Significant improvement of SCORAD	Lip swelling, numbness, pruritus	[171]
Randomized controlled trial	HDM	6 months	14	Moisturizers, antihistamine and mild-potency anti-inflammatory topical treatments	SL	Significant improvement of SCORAD and TEWL	Not available	[172]
Randomized, double-blind, placebo-controlled trial	HDM	18 months	66	Topical corticosteroids, topical immunosuppressors, and systemic immunosuppressants	SL	Significant improvement of SCORAD	Vomiting, abdominal pain, aphthous ulcer, alopecia, dyspnea	[173]
Randomized, placebo-controlled, double-blind trial	HDM	12 months	37	Oral antihistamines, topical medications	SC	Significant improvement of EASI	Mild local reaction, transient urticaria	[174]
Multi-centre, randomized, double-blind, placebo-controlled study	HDM	36 weeks	239	Mometasone furoate cream, levocetirizine hydrochloride tablets, mupirocin ointment, clarithromycin tablets	SL	Significant improvement of SCORAD and SLA	Swelling in tough and lips, throat pain, diarrhoea, itching, numb in mouth	[175]
Randomized controlled study	HDM	24 months	96	Oral levocetirizine hydrochloride tablets, topical fluticasone	SL	Significant reduction of SCORAD	Transient oral itching, gastrointestinal discomfort	[176]
Randomized controlled study	HDM	12 months	107	Oral antihistamines and topical medications	SL	Significant increase of serum-specific IgG4 level	Transient oral itching, gastrointestinal discomfort	[177]
Randomized, double-blind, placebo-controlled study	HDM	18 months	56	Short term use (3 days) of topical fluticasone propionate and/or oral hydroxyzine	SL	Significant reduction of SCORAD in mild-moderate patients	Tiredness, oral itching, headache, mouth, lips, and face swelling	[178]
Observational study	HDM; cat/dog dander	2–58 months	19	Topical treatment and/or oral antihistamines	SL	Significant improvement of IGA and EASI	Not available	[179]
Multi-centre randomized, double-blind, placebo-controlled parallel group trial	HDM	18 months	168	Topical and (as necessary) systemic medication	SC	Significant reduction of SCORAD in severe AD patients	Flare-ups of eczematous and urticarial lesions, symptoms of rhinitis, pruritus, transient headache, and asthma	[180]

AD: atopic dermatitis; AIT: allergen immunotherapy; EASI: eczema area and severity index; HDM: house dust mite; IGA: investigator global assessment; SC: subcutaneous; SL: sublingual; SLA: skin lesion area; SCORAD: scoring atopic dermatitis; TEWL: transepithelial water loss

Declarations

Author contributions

GTS: Conceptualization, Writing—original draft, Writing—review & editing. EAF and MM: Writing—original draft. KN: Writing—review & editing. SB: Conceptualization, Writing—review & editing, Supervision, Funding acquisition. All authors read and approved the submitted version.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

This research was funded by the South African Research Chairs Initiative of the Department of Science and Technology (DST) and the National Research Foundation (NRF) [47904] of South Africa. The NRF and the South African Research Chair in Cancer Biotechnology have provided bursaries to support students contributing to this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Butala S, Castelo-Soccio L, Seshadri R, Simpson EL, O’Shea JJ, Bieber T, et al. Biologic Versus Small Molecule Therapy for Treating Moderate to Severe Atopic Dermatitis: Clinical Considerations. J Allergy Clin Immunol Pract. 2023;11:1361–73. [DOI] [PubMed] [PMC]

Yepes-Nuñez JJ, Guyatt GH, Gómez-Escobar LG, Pérez-Herrera LC, Chu AWL, Ceccaci R, et al. Allergen immunotherapy for atopic dermatitis: Systematic review and meta-analysis of benefits and harms. J Allergy Clin Immunol. 2023;151:147–58. [DOI] [PubMed]

Najera J, Hao J. Recent advance in mesenchymal stem cells therapy for atopic dermatitis. J Cell Biochem. 2023;124:181–7. [DOI] [PubMed]

GBD 2019 IMID Collaborators. Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019. EClinicalMedicine. 2023;64:102193. [DOI] [PubMed] [PMC]

Zhou S, Qi F, Gong Y, Zhang J, Zhu B. Biological Therapies for Atopic Dermatitis: A Systematic Review. Dermatology. 2021;237:542–52. [DOI] [PubMed]

Müller S, Maintz L, Bieber T. Treatment of atopic dermatitis: Recently approved drugs and advanced clinical development programs. Allergy. 2024;79:1501–15. [DOI] [PubMed]

Simpson EL, Bruin-Weller M, Flohr C, Ardern-Jones MR, Barbarot S, Deleuran M, et al. When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council. J Am Acad Dermatol. 2017;77:623–33. [DOI] [PubMed]

Sidbury R, Davis DM, Cohen DE, Cordoro KM, Berger TG, Bergman JN, 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;71:327–49. [DOI] [PubMed] [PMC]

Eichenfield LF, Tom WL, Berger TG, Krol A, Paller AS, Schwarzenberger K, et al. Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116–32. [DOI] [PubMed] [PMC]

10.

Moyle M, Cevikbas F, Harden JL, Guttman-Yassky E. Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches. Exp Dermatol. 2019;28:756–68. [DOI] [PubMed] [PMC]

11.

Akinlade B, Guttman-Yassky E, de Bruin-Weller M, Simpson EL, Blauvelt A, Cork MJ, et al. Conjunctivitis in dupilumab clinical trials. Br J Dermatol. 2019;181:459–73. [DOI] [PubMed] [PMC]

12.

Rodenbeck DL, Silverberg JI, Silverberg NB. Phototherapy for atopic dermatitis. Clin Dermatol. 2016;34:607–13. [DOI] [PubMed]

13.

Shi C, Pei S, Ding Y, Tao C, Zhu Y, Peng Y, et al. Exosomes with overexpressed miR 147a suppress angiogenesis and infammatory injury in an experimental model of atopic dermatitis. Sci Rep. 2023;13:8904. [DOI] [PubMed] [PMC]

14.

Yang Z, Zeng B, Wang C, Wang H, Huang P, Pan Y. MicroRNA-124 alleviates chronic skin inflammation in atopic eczema via suppressing innate immune responses in keratinocytes. Cell Immunol. 2017;319:53–60. [DOI] [PubMed]

15.

Zeng Y, Nguyen GH, Jin H. MicroRNA-143 inhibits IL-13-induced dysregulation of the epidermal barrier-related proteins in skin keratinocytes via targeting to IL-13Rα1. Mol Cell Biochem. 2016;416:63–70. [DOI] [PubMed]

16.

Rebane A, Runnel T, Aab A, Maslovskaja J, Rückert B, Zimmermann M, et al. MicroRNA-146a alleviates chronic skin inflammation in atopic dermatitis through suppression of innate immune responses in keratinocytes. J Allergy Clin Immunol. 2014;134:836–47, e11. [DOI] [PubMed]

17.

Yan C, Ying J, Lu W, Changzhi Y, Qihong Q, Jingzhu M, et al. MiR-1294 suppresses ROS-dependent inflammatory response in atopic dermatitis via restraining STAT3/NF-κB pathway. Cell Immunol. 2022;371:104452. [DOI] [PubMed]

18.

Mitamura Y, Nunomura S, Nanri Y, Ogawa M, Yoshihara T, Masuoka M, et al. The IL-13/periostin/IL-24 pathway causes epidermal barrier dysfunction in allergic skin inflammation. Allergy. 2018;73:1881–91. [DOI] [PubMed]

19.

Chan OM, Xu W, Cheng NS, Leung ASY, Ching JYL, Fong BLY, et al. A novel infant microbiome formula (SIM03) improved eczema severity and quality of life in preschool children. Sci Rep. 2024;14:3168. [DOI] [PubMed] [PMC]

20.

Gürtler A, Rades T, Heinz A. Electrospun fibers for the treatment of skin diseases. J Control Release. 2023;363:621–40. [DOI] [PubMed]

21.

Fu Z, Li S, Han S, Shi C, Zhang Y. Antibody drug conjugate: the “biological missile” for targeted cancer therapy. Signal Transduct Target Ther. 2022;7:93. [DOI] [PubMed] [PMC]

22.

Pal LB, Bule P, Khan W, Chella N. An Overview of the Development and Preclinical Evaluation of Antibody-Drug Conjugates for Non-Oncological Applications. Pharmaceutics. 2023;15:1807. [DOI] [PubMed] [PMC]

23.

Dragovich PS. Antibody-Drug Conjugates for Immunology. J Med Chem. 2022;65:4496–9. [DOI] [PubMed]

24.

Yu S, Pearson AD, Lim RK, Rodgers DT, Li S, Parker HB, et al. Targeted Delivery of an Anti-inflammatory PDE4 Inhibitor to Immune Cells via an Antibody-drug Conjugate. Mol Ther. 2016;24:2078–89. [DOI] [PubMed] [PMC]

25.

Rodak A, Stadlbauer K, Bobbili MR, Smrzka O, Rüker F, Knopp GW. Development of a Cytotoxic Antibody-Drug Conjugate Targeting Membrane Immunoglobulin E-Positive Cells. Int J Mol Sci. 2023;24:14997. [DOI] [PubMed] [PMC]

26.

Everts M, Kok RJ, Asgeirsdóttir SA, Melgert BN, Moolenaar TJM, Koning GA, et al. Selective intracellular delivery of dexamethasone into activated endothelial cells using an E-selectin-directed immunoconjugate. J Immunol. 2002;168:883–9. [DOI] [PubMed]

27.

Graversen JH, Svendsen P, Dagnæs-Hansen F, Dal J, Anton G, Etzerodt A, et al. Targeting the hemoglobin scavenger receptor CD163 in macrophages highly increases the anti-inflammatory potency of dexamethasone. Mol Ther. 2012;20:1550–8. [DOI] [PubMed] [PMC]

28.

Barth S. Recombinant immunotoxins--the next generation. Curr Pharm Des. 2009;15:2650–1. [DOI] [PubMed]

29.

Mungra N, Jordaan S, Hlongwane P, Naran K, Chetty S, Barth S. Targeted human cytolytic fusion proteins at the cutting edge: harnessing the apoptosis-inducing properties of human enzymes for the selective elimination of tumor cells. Oncotarget. 2019;10:897–915. [DOI] [PubMed] [PMC]

30.

Akinrinmade OA, Chetty S, Daramola AK, Islam M, Thepen T, Barth S. CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases. Biomedicines. 2017;5:56. [DOI] [PubMed] [PMC]

31.

Ribbert T, Thepen T, Tur MK, Fischer R, Huhn M, Barth S. Recombinant, ETA’-based CD64 immunotoxins: improved efficacy by increased valency, both in vitro and in vivo in a chronic cutaneous inflammation model in human CD64 transgenic mice. Br J Dermatol. 2010;163:279–86. [DOI] [PubMed]

32.

Thepen T, van Vuuren AJ, Kiekens RC, Damen CA, Vooijs WC, van De Winkel JG. Resolution of cutaneous inflammation after local elimination of macrophages. Nat Biotechnol. 2000;18:48–51. [DOI] [PubMed]

33.

Hristodorov D, Mladenov R, von Felbert V, Huhn M, Fischer R, Barth S, et al. Targeting CD64 mediates elimination of M1 but not M2 macrophages in vitro and in cutaneous inflammation in mice and patient biopsies. MAbs. 2015;7:853–62. [DOI] [PubMed] [PMC]

34.

Jiemy WF, Hiew LF, Sha HX, In LLA, Hwang JS. Evaluation of Hydra HALT-1 as a toxin moiety for recombinant immunotoxin. BMC Biotechnol. 2020;20:31. [DOI] [PubMed] [PMC]

35.

Hristodorov D, Mladenov R, Fischer R, Barth S, Thepen T. Fully human MAP-fusion protein selectively targets and eliminates proliferating CD64+ M1 macrophages. Immunol Cell Biol. 2016;94:470–8. [DOI] [PubMed]

36.

El-Kadiry AE, Rafei M, Shammaa R. Cell Therapy: Types, Regulation, and Clinical Benefits. Front Med (Lausanne). 2021;8:756029. [DOI] [PubMed] [PMC]

37.

Pittenger MF, Discher DE, Péault BM, Phinney DG, Hare JM, Caplan AI. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4:22. [DOI] [PubMed] [PMC]

38.

de Oliveira Ramos F, Malard PF, Brunel HDSS, Paludo GR, de Castro MB, da Silva PHS, et al. Canine atopic dermatitis attenuated by mesenchymal stem cells. J Adv Vet Anim Res. 2020;7:554–65. [DOI] [PubMed] [PMC]

39.

Dias IE, Pinto PO, Barros LC, Viegas CA, Dias IR, Carvalho PP. Mesenchymal stem cells therapy in companion animals: useful for immune-mediated diseases? BMC Vet Res. 2019;15:358. [DOI] [PubMed] [PMC]

40.

Na K, Yoo HS, Zhang YX, Choi M, Lee K, Yi TG, et al. Bone marrow-derived clonal mesenchymal stem cells inhibit ovalbumin-induced atopic dermatitis. Cell Death Dis. 2014;5:e1345. [DOI] [PubMed] [PMC]

41.

Kim H, Yun J, Shin T, Lee S, Lee B, Yu K, et al. Human umbilical cord blood mesenchymal stem cell-derived PGE2 and TGF-β1 alleviate atopic dermatitis by reducing mast cell degranulation. Stem Cells. 2015;33:1254–66. [DOI] [PubMed]

42.

Shin T, Lee B, Choi SW, Shin J, Kang I, Lee JY, et al. Human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis via regulation of B lymphocyte maturation. Oncotarget. 2017;8:512–22. [DOI] [PubMed] [PMC]

43.

Kim M, Lee S, Kim Y, Kwon Y, Park Y, Lee H, et al. Human Adipose Tissue-Derived Mesenchymal Stem Cells Attenuate Atopic Dermatitis by Regulating the Expression of MIP-2, miR-122a-SOCS1 Axis, and Th1/Th2 Responses. Front Pharmacol. 2018;9:1175. [DOI] [PubMed] [PMC]

44.

Sah SK, Agrahari G, Nguyen CT, Kim Y, Kang K, Kim T. Enhanced therapeutic effects of human mesenchymal stem cells transduced with superoxide dismutase 3 in a murine atopic dermatitis-like skin inflammation model. Allergy. 2018;73:2364–76. [DOI] [PubMed]

45.

Lee B, Kim J, Lee JY, Kang I, Shin N, Lee S, et al. Disease-specific primed human adult stem cells effectively ameliorate experimental atopic dermatitis in mice. Theranostics. 2019;9:3608–21. [DOI] [PubMed] [PMC]

46.

Park A, Park H, Yoon J, Kang D, Kang M, Park Y, et al. Priming with Toll-like receptor 3 agonist or interferon-gamma enhances the therapeutic effects of human mesenchymal stem cells in a murine model of atopic dermatitis. Stem Cell Res Ther. 2019;10:66. [DOI] [PubMed] [PMC]

47.

Kim C, Hong S, Kim S, Yu JI, Jung S, Bang CH, et al. Skin repair and immunoregulatory effects of myeloid suppressor cells from human cord blood in atopic dermatitis. Front Immunol. 2024;14:1263646. [DOI] [PubMed] [PMC]

48.

Lee H, Lee TW, Chandrasekharan A, Sung S, Yim S, Kim S, et al. Injectable Self-Crosslinkable Thiolated Hyaluronic Acid for Stem Cell Therapy of Atopic Dermatitis. ACS Biomater Sci Eng. 2022;8:1613–22. [DOI] [PubMed]

49.

Pang QQ, Noh BW, Park HS, Kim YS, Kim JH, Cho EJ. Improvement Effect of Membrane-Free Stem Cell Extract on Atopic Dermatitis in NC/Nga Mice. Appl Sci. 2023;13:1–13. [DOI]

50.

Guan J, Li Y, Lu F, Feng J. Adipose-derived stem cells ameliorate atopic dermatitis by suppressing the IL-17 expression of Th17 cells in an ovalbumin-induced mouse model. Stem Cell Res Ther. 2022;13:98. [DOI] [PubMed] [PMC]

51.

Hua C, Liang Q, Chen S, Zhu J, Tang Y, Chen X, et al. Human umbilical cord mesenchymal stem cell treatment alleviates symptoms in an atopic dermatitis-like mouse model. Stem Cell Res Ther. 2023;14:147. [DOI] [PubMed] [PMC]

52.

Murer P, Neri D. Antibody-cytokine fusion proteins: A novel class of biopharmaceuticals for the therapy of cancer and of chronic inflammation. N Biotechnol. 2019;52:42–53. [DOI] [PubMed] [PMC]

53.

Zhang J, An J. Cytokines, inflammation, and pain. Int Anesthesiol Clin. 2007;45:27–37. [DOI] [PubMed] [PMC]

54.

Hemmerle T, Zgraggen S, Matasci M, Halin C, Detmar M, Neri D. Antibody-mediated delivery of interleukin 4 to the neo-vasculature reduces chronic skin inflammation. J Dermatol Sci. 2014;76:96–103. [DOI] [PubMed]

55.

Rybchenko VS, Aliev TK, Panina AA, Kirpichnikov MP, Dolgikh DA. Targeted Cytokine Delivery for Cancer Treatment: Engineering and Biological Effects. Pharmaceutics. 2023;15:336. [DOI] [PubMed] [PMC]

56.

Huggenberger R, Ullmann S, Proulx ST, Pytowski B, Alitalo K, Detmar M. Stimulation of lymphangiogenesis via VEGFR-3 inhibits chronic skin inflammation. J Exp Med. 2010;207:2255–69. [DOI] [PubMed] [PMC]

57.

Schwager S, Renner S, Hemmerle T, Karaman S, Proulx ST, Fetz R, et al. Antibody-mediated delivery of VEGF-C potently reduces chronic skin inflammation. JCI Insight. 2018;3:e124850. [DOI] [PubMed] [PMC]

58.

Cousin N, Bartel S, Scholl J, Tacconi C, Egger A, Thorhallsdottir G, et al. Antibody-Mediated Delivery of VEGF-C Promotes Long-Lasting Lymphatic Expansion That Reduces Recurrent Inflammation. Cells. 2022;12:172. [DOI] [PubMed] [PMC]

59.

Chiricozzi A, Krueger JG. IL-17 targeted therapies for psoriasis. Expert Opin Investig Drugs. 2013;22:993–1005. [DOI] [PubMed]

60.

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. [DOI] [PubMed]

61.

Renert-Yuval Y, Guttman-Yassky E. Monoclonal antibodies for the treatment of atopic dermatitis. Curr Opin Allergy Clin Immunol. 2018;18:356–64. [DOI] [PubMed]

62.

Zhao Y, Wu L, Lu Q, Gao X, Zhu X, Yao X, et al. The efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis: a randomized, double-blind, placebo-controlled study. Br J Dermatol. 2022;186:633–41. [DOI] [PubMed] [PMC]

63.

Popovic B, Breed J, Rees DG, Gardener MJ, Vinall LMK, 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;429:208–19. [DOI] [PubMed]

64.

Ultsch M, Bevers J, Nakamura G, Vandlen R, Kelley RF, Wu LC, et al. Structural basis of signaling blockade by anti-IL-13 antibody Lebrikizumab. J Mol Biol. 2013;425:1330–9. [DOI] [PubMed]

65.

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. [DOI] [PubMed]

66.

Gittler JK, Shemer A, Suárez-Fariñas M, Fuentes-Duculan J, Gulewicz KJ, Wang CQF, et al. Progressive activation of Th2/Th22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130:1344–54. [DOI] [PubMed] [PMC]

67.

Nograles KE, Zaba LC, Shemer A, Fuentes-Duculan J, Cardinale I, Kikuchi T, 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;123:1244–52, e2. [DOI] [PubMed] [PMC]

68.

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. [DOI] [PubMed] [PMC]

69.

Zheng Y, Danilenko DM, Valdez P, Kasman I, Eastham-Anderson J, Wu J, et al. Interleukin-22, a T_H17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis. Nature. 2007;445:648–51. [DOI] [PubMed]

70.

Vakharia PP, Silverberg JI. Monoclonal Antibodies for Atopic Dermatitis: Progress and Potential. BioDrugs. 2017;31:409–22. [DOI] [PubMed]

71.

Khattri S, Brunner PM, Garcet S, Finney R, Cohen SR, Oliva M, et al. Efficacy and safety of ustekinumab treatment in adults with moderate-to-severe atopic dermatitis. Exp Dermatol. 2017;26:28–35. [DOI] [PubMed] [PMC]

72.

Silverberg JI, Strober B, Feinstein B, Xu J, Guttman-Yassky E, Simpson EL, et al. Efficacy and safety of rademikibart (CBP-201), a next-generation mAb targeting IL-4Rα, in adults with moderate to severe atopic dermatitis: A phase 2 randomized trial (CBP-201-WW001). J Allergy Clin Immunol. 2024;153:1040–9, e12. [DOI] [PubMed]

73.

Wynne CJ, Cole A, Lemech C, Wang G, Zhang Y, Chen B, et al. Safety, Pharmacokinetics and Preliminary Efficacy of IL4-Rα Monoclonal Antibody AK120 in Both Healthy and Atopic Dermatitis Subjects: A Phase I, Randomized, Two-Part, Double-Blind, Placebo-Controlled, Dose-Escalation, First-In-Human Clinical Study. Dermatol Ther (Heidelb). 2023;13:2357–73. [DOI] [PubMed] [PMC]

74.

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. Lancet. 2022;400:908–19. [DOI] [PubMed]

75.

Beck LA, Thaçi D, Hamilton JD, Graham NM, Bieber T, Rocklin R, et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis. N Engl J Med. 2014;371:130–9. [DOI] [PubMed]

76.

Simpson EL, Bieber T, Guttman-Yassky E, Beck LA, Blauvelt A, Cork MJ, et al.; SOLO 1 and SOLO 2 Investigators. Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis. N Engl J Med. 2016;375:2335–48. [DOI] [PubMed]

77.

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. [DOI] [PubMed]

78.

Wu JJ, Spelman L, Tan JL, Etoh T, Zhang H, Shumel B, et al. Dupilumab Maintains Long-Term Disease Control in Adults with Moderate-to-Severe Atopic Dermatitis as Measured by Well-Controlled Weeks: Results From the LIBERTY AD CHRONOS Clinical Trial. Dermatol Ther (Heidelb). 2021;11:327–30. [DOI] [PubMed] [PMC]

79.

de Bruin-Weller M, Thaçi D, Smith CH, Reich K, Cork MJ, Radin A, 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;178:1083–101. [DOI] [PubMed]

80.

Silverberg JI, Adam DN, Zirwas M, Kalia S, Gutermuth J, Pinter A, 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;23:547–59. [DOI] [PubMed] [PMC]

81.

Simpson EL, Blauvelt A, Silverberg JI, Cork MJ, Katoh N, Mark T, et al. Tralokinumab Provides Clinically Meaningful Responses at Week 16 in Adults with Moderate-to-Severe Atopic Dermatitis Who Do Not Achieve IGA 0/1. Am J Clin Dermatol. 2024;25:139–48. [DOI] [PubMed] [PMC]

82.

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;159:596–605. [DOI] [PubMed] [PMC]

83.

Paller AS, Flohr C, Eichenfield LF, Irvine AD, Weisman J, Soung J, et al. Safety and Efficacy of Lebrikizumab in Adolescent Patients with Moderate-to-Severe Atopic Dermatitis: A 52-Week, Open-Label, Phase 3 Study. Dermatol Ther (Heidelb). 2023;13:1517–34. [DOI] [PubMed] [PMC]

84.

Blauvelt A, Thyssen JP, Guttman-Yassky E, Bieber T, Serra-Baldrich E, Simpson 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;188:740–48. [DOI] [PubMed]

85.

Ungar B, Pavel AB, Li R, Kimmel G, Nia J, Hashim P, et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis. J Allergy Clin Immunol. 2021;147:394–97. [DOI] [PubMed]

86.

Tyring SK, Rich P, Tada Y, Beeck S, Messina I, Liu J, et al. Risankizumab in Patients with Moderate-to-Severe Atopic Dermatitis: A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study. Dermatol Ther (Heidelb). 2023;13:595–608. [DOI] [PubMed] [PMC]

87.

Kabashima K, Matsumura T, Komazaki H, Kawashima M; Nemolizumab JP01 and JP02 Study Group. 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;186:642–51. [DOI] [PubMed] [PMC]

88.

Kabashima K, Matsumura T, Komazaki H, Kawashima M; Group NS; Abe M, et al.; Nemolizumab-JP01 Study Group. Trial of Nemolizumab and Topical Agents for Atopic Dermatitis with Pruritus. N Engl J Med. 2020;383:141–50. [DOI] [PubMed]

89.

Ruzicka T, Hanifin JM, Furue M, Pulka G, Mlynarczyk I, Wollenberg A, et al.; XCIMA Study Group. Anti-Interleukin-31 Receptor A Antibody for Atopic Dermatitis. N Engl J Med. 2017;376:826–35. [DOI] [PubMed]

90.

Silverberg JI, Pinter A, Alavi A, Lynde C, Bouaziz J, Wollenberg A, et al. Nemolizumab is associated with a rapid improvement in atopic dermatitis signs and symptoms: subpopulation (EASI ≥ 16) analysis of randomized phase 2B study. J Eur Acad Dermatol Venereol. 2021;35:1562–68. [DOI] [PubMed]

91.

Igarashi A, Katsunuma T, Matsumura T, Komazaki H; Group NS; Takahashi H, et al.; Nemolizumab-JP04 Study Group. 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, randomized, double-blind, placebo-controlled, multicentre study. Br J Dermatol. 2023;190:20–8. [DOI] [PubMed]

92.

Maurer M, Cheung DS, Theess W, Yang X, Dolton M, Guttman A, et al. Phase 2 randomized clinical trial of astegolimab in patients with moderate to severe atopic dermatitis. J Allergy Clin Immunol. 2022;150:1517–24. [DOI] [PubMed]

93.

Chen Y, Gutowska-Owsiak D, Hardman CS, Westmoreland M, MacKenzie T, Cifuentes L, 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:eaax2945. [DOI] [PubMed]

94.

Bissonnette R, Abramovits W, Proulx C, Lee P, Yassky EG, Zovko E, 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 II a study. J Eur Acad Dermatology Venereol. 2023;37:549–57. [DOI] [PubMed]

95.

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 Allergy Clin Immunol. 2019;144:482–93, e7. [DOI] [PubMed]

96.

Late-breaking amlitelimab Phase 2b data presented at EADV show potential best-in-class profile in atopic dermatitis [Internet]. Sanofi; c2004–2024 [cited 2023 Oct 13]. Available from: https://www.sanofi.com/en/media-room/press-releases/2023/2023-10-13-14-00-00-2760021/

97.

Weidinger S, Bieber T, Cork MJ, Reich A, Wilson R, Quaratino S, 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;189:531–9. [DOI] [PubMed]

98.

Iannelli M, Caminiti L, Vaccaro M, Marafioti I, Spinuzza A, Panasiti I, et al. Omalizumab for treatment of refractory severe atopic dermatitis. A pediatric perspective. Dermatol Ther. 2020;33:e13519. [DOI] [PubMed]

99.

Chan S, Cornelius V, Cro S, Harper JI, Lack G. Treatment Effect of Omalizumab on Severe Pediatric Atopic Dermatitis: The ADAPT Randomized Clinical Trial. JAMA Pediatr. 2020;174:29–37. [DOI] [PubMed] [PMC]

100.

Chan S, Cornelius V, Chen T, Radulovic S, Wan M, Jahan R, et al. Atopic Dermatitis Anti-IgE Paediatric Trial (ADAPT): the role of anti-IgE in severe paediatric eczema: study protocol for a randomised controlled trial. Trials. 2017;18:136. [DOI] [PubMed] [PMC]

101.

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. [DOI] [PubMed]

102.

Worm M, Francuzik W, Kraft M, Alexiou A. Modern therapies in atopic dermatitis: biologics and small molecule drugs. J Dtsch Dermatol Ges. 2020;18:1085–92. [DOI] [PubMed]

103.

Bao L, Zhang H, Chan LS. The involvement of the JAK-STAT signaling pathway in chronic inflammatory skin disease atopic dermatitis. JAKSTAT. 2013;2:e24137. [DOI] [PubMed] [PMC]

104.

Guttman-Yassky E, Hanifin JM, Boguniewicz M, Wollenberg A, Bissonnette R, Purohit V, et al. The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition. Exp Dermatol. 2019;28:3–10. [DOI] [PubMed]

105.

Raker VK, Becker C, Steinbrink K. The cAMP Pathway as Therapeutic Target in Autoimmune and Inflammatory Diseases. Front Immunol. 2016;7:123. [DOI] [PubMed] [PMC]

106.

Schafer PH, Truzzi F, Parton A, Wu L, Kosek J, Zhang L, et al. Phosphodiesterase 4 in inflammatory diseases: Effects of apremilast in psoriatic blood and in dermal myofibroblasts through the PDE4/CD271 complex. Cell Signal. 2016;28:753–63. [DOI] [PubMed]

107.

Wittmann M, Helliwell PS. Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases. Dermatol Ther (Heidelb). 2013;3:1–15. [DOI] [PubMed] [PMC]

108.

Benedetto AD, Yoshida T, Fridy S, Park JS, Kuo I, Beck LA. Histamine and Skin Barrier: Are Histamine Antagonists Useful for the Prevention or Treatment of Atopic Dermatitis? J Clin Med. 2015;4:741–55. [DOI] [PubMed] [PMC]

109.

Rathinasamy A, Czeloth N, Pabst O, Förster R, Bernhardt G. The origin and maturity of dendritic cells determine the pattern of sphingosine 1-phosphate receptors expressed and required for efficient migration. J Immunol. 2010;185:4072–81. [DOI] [PubMed]

110.

Silverberg JI, Bissonnette R, Kircik L, Murrell DF, Selfridge A, Liu K, et al. Efficacy and safety of etrasimod, a sphingosine 1-phosphate receptor modulator, in adults with moderate-to-severe atopic dermatitis (ADVISE). J Eur Acad Dermatol Venereol. 2023;37:1366–74. [DOI] [PubMed]

111.

Silverberg JI, de Bruin-Weller M, Bieber T, Soong W, Kabashima K, Costanzo A, et al. Upadacitinib plus topical corticosteroids in atopic dermatitis: Week 52 AD Up study results. J Allergy Clin Immunol. 2022;149:977–87, e14. [DOI] [PubMed]

112.

Guttman-Yassky E, Teixeira HD, Simpson EL, Papp KA, Pangan AL, Blauvelt A, 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;397:2151–68. [DOI] [PubMed]

113.

Reich K, Teixeira HD, de Bruin-Weller M, Bieber T, Soong W, Kabashima K, 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;397:2169–81. [DOI] [PubMed]

114.

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, placebo-controlled trial. J Allergy Clin Immunol. 2020;145:877–84. [DOI] [PubMed]

115.

Shi VY, Bhutani T, Fonacier L, Deleuran M, Shumack S, Valdez H, 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;87:351–8. [DOI] [PubMed]

116.

Simpson EL, Silverberg JI, Thyssen JP, Viguier M, Thaçi D, de Bruin-Weller M, et al. Efficacy and Safety of Abrocitinib in Patients with Severe and/or Difficult-to-Treat Atopic Dermatitis: A Post Hoc Analysis of the Randomized Phase 3 JADE COMPARE Trial. Am J Clin Dermatol. 2023;24:609–21. [DOI] [PubMed] [PMC]

117.

Bieber T, Simpson EL, Silverberg JI, Thaçi D, Paul C, Pink AE, et al.; JADE COMPARE Investigators. Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis. N Engl J Med. 2021;384:1101–12. [DOI] [PubMed]

118.

Silverberg JI, Simpson EL, Thyssen JP, Gooderham M, Chan G, Feeney C, et al. Efficacy and Safety of Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020;156:863–73. [DOI] [PubMed] [PMC]

119.

Simpson EL, Sinclair R, Forman S, Wollenberg A, Aschoff R, Cork M, 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;396:255–66. [DOI] [PubMed]

120.

Gooderham MJ, Forman SB, Bissonnette R, Beebe JS, Zhang W, Banfield C, et al. Efficacy and Safety of Oral Janus Kinase 1 Inhibitor Abrocitinib for Patients With Atopic Dermatitis: A Phase 2 Randomized Clinical Trial. JAMA Dermatol. 2019;155:1371–79. [DOI] [PubMed] [PMC]

121.

Zhao Y, Zhang L, Ding Y, Tao X, Ji C, Dong X, et al. Efficacy and Safety of SHR0302, a Highly Selective Janus Kinase 1 Inhibitor, in Patients with Moderate to Severe Atopic Dermatitis: A Phase II Randomized Clinical Trial. Am J Clin Dermatol. 2021;22:877–89. [DOI] [PubMed] [PMC]

122.

Simpson EL, Forman S, Silverberg JI, Zirwas M, Maverakis E, Han G, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis: Results from a randomized monotherapy phase 3 trial in the United States and Canada (BREEZE-AD5). J Am Acad Dermatol. 2021;85:62–70. [DOI] [PubMed]

123.

Simpson EL, Lacour J, Spelman L, Galimberti R, Eichenfield LF, Bissonnette R, et al. Baricitinib in patients with moderate-to-severe atopic dermatitis and inadequate response to topical corticosteroids: results from two randomized monotherapy phase III trials. Br J Dermatol. 2020;183:242–55. [DOI] [PubMed]

124.

Guttman-Yassky E, Silverberg JI, Nemoto O, Forman SB, Wilke A, Prescilla R, et al. Baricitinib in adult patients with moderate-to-severe atopic dermatitis: A phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study. J Am Acad Dermatol. 2019;80:913–21, e9. [DOI] [PubMed]

125.

King B, Maari C, Lain E, Silverberg JI, Issa M, Holzwarth K, et al. Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials. Am J Clin Dermatol. 2021;22:395–405. [DOI] [PubMed] [PMC]

126.

Wollenberg A, Nakahara T, Maari C, Peris K, Lio P, Augustin M, et al. Impact of baricitinib in combination with topical steroids on atopic dermatitis symptoms, quality of life and functioning in adult patients with moderate-to-severe atopic dermatitis from the BREEZE-AD7 Phase 3 randomized trial. J Eur Acad Dermatol Venereol. 2021;35:1543–52. [DOI] [PubMed] [PMC]

127.

Reich K, Kabashima K, Peris K, Silverberg JI, Eichenfield LF, Bieber T, et al. Efficacy and Safety of Baricitinib Combined With Topical Corticosteroids for Treatment of Moderate to Severe Atopic Dermatitis: A Randomized Clinical Trial. JAMA Dermatol. 2020;156:1333–43. [DOI] [PubMed] [PMC]

128.

Silverberg JI, Simpson EL, Wollenberg A, Bissonnette R, Kabashima K, DeLozier AM, et al. Long-term Efficacy of Baricitinib in Adults With Moderate to Severe Atopic Dermatitis Who Were Treatment Responders or Partial Responders: An Extension Study of 2 Randomized Clinical Trials. JAMA Dermatol. 2021;157:691–9. [DOI] [PubMed] [PMC]

129.

Papp K, Szepietowski JC, Kircik L, Toth D, Eichenfield LF, Leung DYM, et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: Results from 2 phase 3, randomized, double-blind studies. J Am Acad Dermatol. 2021;85:863–72. [DOI] [PubMed]

130.

Kim BS, Sun K, Papp K, Venturanza M, Nasir A, Kuligowski ME. Effects of ruxolitinib cream on pruritus and quality of life in atopic dermatitis: Results from a phase 2, randomized, dose-ranging, vehicle-and active-controlled study. J Am Acad Dermatol. 2020;82:1305–13. [DOI] [PubMed]

131.

Kim BS, Howell MD, Sun K, Papp K, Nasir A, Kuligowski ME, et al.; INCB 18424-206 Study Investigators. Treatment of atopic dermatitis with ruxolitinib cream (JAK1/JAK2 inhibitor) or triamcinolone cream. J Allergy Clin Immunol. 2020;145:572–82. [DOI] [PubMed]

132.

Bissonnette R, Papp KA, Poulin Y, Gooderham M, Raman M, Mallbris L, et al. Topical tofacitinib for atopic dermatitis: a phase IIa randomized trial. Br J Dermatol. 2016;175:902–11. [DOI] [PubMed]

133.

Changelian P, Xu C, Mnich S, Hope H, Kostecki K, Hirsch J, et al. ATI-1777, a Topical Jak1/3 Inhibitor, May Benefit Atopic Dermatitis without Systemic Drug Exposure: Results from Preclinical Development and Phase 2a Randomized Control Study ATI-1777-AD-201. JID Innov. 2023;4:100251. [DOI] [PubMed] [PMC]

134.

Smith S, Bhatia N, Shanler SD, Demoor R, Schnyder J. 16089 Safety of ATI-502, a novel topical JAK1/3 inhibitor, in adults with moderate to severe atopic dermatitis: Results from a phase 2a open-label trial. J Am Acad Dermatol. 2020;83:AB170. [DOI]

135.

Landis MN, Arya M, Smith S, Draelos Z, Usdan L, Tarabar S, et al. Efficacy and safety of topical brepocitinib for the treatment of mild-to-moderate atopic dermatitis: a phase IIb, randomized, double-blind, vehicle-controlled, dose-ranging and parallel-group study. Br J Dermatol. 2022;187:878–87. [DOI] [PubMed] [PMC]

136.

Nakagawa H, Nemoto O, Yamada H, Nagata T, Ninomiya N. Phase 1 studies to assess the safety, tolerability and pharmacokinetics of JTE-052 (a novel Janus kinase inhibitor) ointment in Japanese healthy volunteers and patients with atopic dermatitis. J Dermatol. 2018;45:701–09. [DOI] [PubMed] [PMC]

137.

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Kaino H, Nagata T. Delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with moderate to severe atopic dermatitis: A phase 3, randomized, double-blind, vehicle-controlled study and an open-label, long-term extension study. J Am Acad Dermatol. 2020;82:823–31. [DOI] [PubMed]

138.

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Oda M, Kabashima K, et al. Phase 2 clinical study of delgocitinib ointment in pediatric patients with atopic dermatitis. J Allergy Clin Immunol. 2019;144:1575–83. [DOI] [PubMed]

139.

Nakagawa H, Nemoto O, Igarashi A, Nagata T. Efficacy and safety of topical JTE-052, a Janus kinase inhibitor, in Japanese adult patients with moderate-to-severe atopic dermatitis: a phase II, multicentre, randomized, vehicle-controlled clinical study. Br J Dermatol. 2018;178:424–32. [DOI] [PubMed]

140.

Nakagawa H, Nemoto O, Igarashi A, Saeki H, Murata R, Kaino H, et al. Long-term safety and efficacy of delgocitinib ointment, a topical Janus kinase inhibitor, in adult patients with atopic dermatitis. J Dermatol. 2020;47:114–20. [DOI] [PubMed] [PMC]

141.

Callender VD, Alexis AF, Gold LFS, Lebwohl MG, Paller AS, Desai SR, et al. Efficacy and Safety of Crisaborole Ointment, 2%, for the Treatment of Mild-to-Moderate Atopic Dermatitis Across Racial and Ethnic Groups. Am J Clin Dermatol. 2019;20:711–23. [DOI] [PubMed] [PMC]

142.

Eichenfield LF, Gower RG, Xu J, Alam MS, Su JC, Myers DE, et al. Once-Daily Crisaborole Ointment, 2%, as a Long-Term Maintenance Treatment in Patients Aged ≥ 3 Months with Mild-to-Moderate Atopic Dermatitis: A 52-Week Clinical Study. Am J Clin Dermatol. 2023;24:623–35. [DOI] [PubMed] [PMC]

143.

Paller AS, Tom WL, Lebwohl MG, Blumenthal RL, Boguniewicz M, Call RS, et al. Efficacy and safety of crisaborole ointment, a novel, nonsteroidal phosphodiesterase 4 (PDE4) inhibitor for the topical treatment of atopic dermatitis (AD) in children and adults. J Am Acad Dermatol. 2016;75:494–503, e6. [DOI] [PubMed]

144.

Saeki H, Imamura T, Yokota D, Tsubouchi H. Difamilast Ointment in Japanese Adult and Pediatric Patients with Atopic Dermatitis: A Phase III, Long-Term, Open-Label Study. Dermatol Ther (Heidelb). 2022;12:1589–601. [DOI] [PubMed] [PMC]

145.

Saeki H, Baba N, Ito K, Yokota D, Tsubouchi H. Difamilast, a selective phosphodiesterase 4 inhibitor, ointment in paediatric patients with atopic dermatitis: a phase III randomized double-blind, vehicle-controlled trial. Br J Dermatol. 2022;186:40–9. [DOI] [PubMed] [PMC]

146.

Saeki H, Ito K, Yokota D, Tsubouchi H. Difamilast ointment in adult patients with atopic dermatitis: A phase 3 randomized, double-blind, vehicle-controlled trial. J Am Acad Dermatol. 2022;86:607–14. [DOI] [PubMed]

147.

Eichenfield L, Boguniewicz M, Simpson E, Blauvelt A, Gooderham M, Lain E, et al. Once-daily roflumilast cream 0.15% for atopic dermatitis: pooled results: from Integument-1/2 phase 3 trials. Ann Allergy, Asthma Immunol. 2023;131:S91. [DOI]

148.

Welsh SE, Xiao C, Kaden AR, Brzezynski JL, Mohrman MA, Wang J, et al. Neurokinin-1 receptor antagonist tradipitant has mixed effects on itch in atopic dermatitis: results from EPIONE, a randomized clinical trial. J Eur Acad Dermatol Venereol. 2021;35:e338–40. [DOI] [PubMed] [PMC]

149.

Guttman-Yassky E, Facheris P, Rosa JCD, Rothenberg-Lausell C, Duca ED, David E, et al. Oral difelikefalin reduces moderate to severe pruritus and expression of pruritic and inflammatory biomarkers in subjects with atopic dermatitis. J Allergy Clin Immunol. 2023;152:916–26. [DOI] [PubMed]

150.

Werfel T, Layton G, Yeadon M, Whitlock L, Osterloh I, Jimenez P, et al. Efficacy and safety of the histamine H₄ receptor antagonist ZPL-3893787 in patients with atopic dermatitis. J Allergy Clin Immunol. 2019;143:1830–37, e4. [DOI] [PubMed]

151.

Czarnowicki T, Dohlman AB, Malik K, Antonini D, Bissonnette R, Chan TC, et al. Effect of short-term liver X receptor activation on epidermal barrier features in mild to moderate atopic dermatitis: A randomized controlled trial. Ann Allergy Asthma Immunol. 2018;120:631–40, e11. [DOI] [PubMed]

152.

Ra JC, Kang SK, Shin IS, Park HG, Joo SA, Kim JG, et al. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells. J Transl Med. 2011;9:181. [DOI] [PubMed] [PMC]

153.

Kim H, Lee JH, Roh K, Jun HJ, Kang K, Kim T. Clinical Trial of Human Umbilical Cord Blood-Derived Stem Cells for the Treatment of Moderate-to-Severe Atopic Dermatitis: Phase I/IIa Studies. Stem Cells. 2017;35:248–55. [DOI] [PubMed]

154.

Kim Y, Ahn H, Lee S, Lee M, Kang K. Effects of conditioned media from human umbilical cord blood-derived mesenchymal stem cells in the skin immune response. Biomed Pharmacother. 2020;131:110789. [DOI] [PubMed]

155.

Shin H, Lee SH, Yoon HS, Heo JH, Lee SB, Byun JW, et al. Long-term efficacy and safety of intravenous injection of clonal mesenchymal stem cells derived from bone marrow in five adults with moderate to severe atopic dermatitis. J Dermatol. 2021;48:1236–42. [DOI] [PubMed]

156.

Hillier A, Griffin CE. The ACVD task force on canine atopic dermatitis (I): incidence and prevalence. Vet Immunol Immunopathol. 2001;81:147–51. [DOI] [PubMed]

157.

Villatoro AJ, Hermida-Prieto M, Fernández V, Fariñas F, Alcoholado C, Rodríguez-García MI, et al. Allogeneic adipose-derived mesenchymal stem cell therapy in dogs with refractory atopic dermatitis: clinical efficacy and safety. Vet Rec. 2018;183:654. [DOI] [PubMed]

158.

Enciso N, Amiel J, Pando J, Enciso J. Multidose intramuscular allogeneic adipose stem cells decrease the severity of canine atopic dermatitis: A pilot study. Vet World. 2019;12:1747–54. [DOI] [PubMed] [PMC]

159.

Kaur G, Ramirez A, Xie C, Clark D, Dong C, Maki C, et al. A double-blinded placebo-controlled evaluation of adipose-derived mesenchymal stem cells in treatment of canine atopic dermatitis. Vet Res Commun. 2022;46:251–60. [DOI] [PubMed]

160.

Black L, Zacharias S, Hughes M, Bautista R, Taechangam N, Sand T. The effect of uterine-derived mesenchymal stromal cells for the treatment of canine atopic dermatitis: A pilot study. Front Vet Sci. 2022;9:1011174. [DOI] [PubMed] [PMC]

161.

Kim S, Lim K, Cho S, Ryu B, Kim C, Park SY, et al. Efficacy of Allogeneic and Xenogeneic Exosomes for the Treatment of Canine Atopic Dermatitis: A Pilot Study. Animals (Basel). 2024;14:282. [DOI] [PubMed] [PMC]

162.

Rostaher A, Fischer NM, Vigani A, Steblaj B, Martini F, Brem S, et al. Hymenoptera Venom Immunotherapy in Dogs: Safety and Clinical Efficacy. Animals (Basel). 2023;13:3002. [DOI] [PubMed] [PMC]

163.

Fritzsching B, Contoli M, Porsbjerg C, Buchs S, Larsen JR, Elliott L, et al. Long-term real-world effectiveness of allergy immunotherapy in patients with allergic rhinitis and asthma: Results from the REACT study, a retrospective cohort study. Lancet Reg Health Eur. 2021;13:100275. [DOI] [PubMed] [PMC]

164.

Darsow U. Allergen-specific immunotherapy for atopic eczema: updated. Curr Opin Allergy Clin Immunol. 2012;12:665–9. [DOI] [PubMed]

165.

Shah D, Hales J, Cooper D, Camp R. Recognition of pathogenically relevant house dust mite hypersensitivity in adults with atopic dermatitis: a new approach? J Allergy Clin Immunol. 2002;109:1012–8. [DOI] [PubMed]

166.

Guo B, Wu K, Chen C, Lin W, Chang Y, Lin M, et al. Advancements in Allergen Immunotherapy for the Treatment of Atopic Dermatitis. Int J Mol Sci. 2024;25:1316. [DOI] [PubMed] [PMC]

167.

Satitsuksanoa P, Angelina A, Palomares O, Akdis M. Mechanisms in AIT: Insights 2021. Allergol Select. 2022;6:259–66. [DOI] [PubMed] [PMC]

168.

Rizk P, Rodenas M, Benedetto AD. Allergen Immunotherapy and Atopic Dermatitis: the Good, the Bad, and the Unknown. Curr Allergy Asthma Rep. 2019;19:57. [DOI] [PubMed]

169.

James C, Bernstein DI. Allergen immunotherapy: an updated review of safety. Curr Opin Allergy Clin Immunol. 2017;17:55–9. [DOI] [PubMed] [PMC]

170.

Kim M, Lee E, Yoon J, Jung S, Song KB, Choi EJ, et al. Sublingual immunotherapy may be effective in reducing house dust mite allergies in children with atopic dermatitis. Acta Paediatr. 2022;111:2142–8. [DOI] [PubMed]

171.

Huang C, Tang J. Sublingual immunotherapy with Dermatophagoides farinae drops for pediatric atopic dermatitis. Int J Dermatol. 2022;61:246–51. [DOI] [PubMed]

172.

Hajdu K, Kapitány A, Dajnoki Z, Soltész L, Baráth S, Hendrik Z, et al. Improvement of clinical and immunological parameters after allergen-specific immunotherapy in atopic dermatitis. J Eur Acad Dermatol Venereol. 2021;35:1357–61. [DOI] [PubMed]

173.

Langer SS, Cardili RN, Melo JML, Ferriani MPL, Moreno AS, Dias MM, et al. Efficacy of House Dust Mite Sublingual Immunotherapy in Patients with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial. J Allergy Clin Immunol Pract. 2022;10:539–49, e7. [DOI] [PubMed]

174.

Bogacz-Piaseczyńska A, Bożek A. The Effectiveness of Allergen Immunotherapy in Adult Patients with Atopic Dermatitis Allergic to House Dust Mites. Medicina (Kaunas). 2022;59:15. [DOI] [PubMed] [PMC]

175.

Liu L, Chen J, Xu J, Yang Q, Gu C, Ni C, et al. Sublingual immunotherapy of atopic dermatitis in mite-sensitized patients: a multi-centre, randomized, double-blind, placebo-controlled study. Artif Cells Nanomed Biotechnol. 2019;47:3540–47. [DOI] [PubMed]

176.

Yu N, Luo H, Liang D, Lu N. Sublingual immunotherapy in mite-sensitized patients with atopic dermatitis: a randomized controlled study. Postepy Dermatol Alergol. 2021;38:69–74. [DOI] [PubMed] [PMC]

177.

Qin Y, Mao J, Sang Y, Li W. Clinical efficacy and compliance of sublingual immunotherapy with Dermatophagoides farinae drops in patients with atopic dermatitis. Int J Dermatol. 2014;53:650–5. [DOI] [PubMed]

178.

Pajno GB, Caminiti L, Vita D, Barberio G, Salzano G, Lombardo F, et al. Sublingual immunotherapy in mite-sensitized children with atopic dermatitis: a randomized, double-blind, placebo-controlled study. J Allergy Clin Immunol. 2007;120:164–70. [DOI] [PubMed]

179.

Chu H, Park KH, Kim SM, Lee J, Park J, Lee KH, et al. Allergen-specific immunotherapy for patients with atopic dermatitis sensitized to animal dander. Immun Inflamm Dis. 2020;8:165–9. [DOI] [PubMed] [PMC]

180.

Novak N, Bieber T, Hoffmann M, Fölster-Holst R, Homey B, Werfel T, et al. Efficacy and safety of subcutaneous allergen-specific immunotherapy with depigmented polymerized mite extract in atopic dermatitis. J Allergy Clin Immunol. 2012;130:925–31, e4. [DOI] [PubMed]

181.

Paiva-Santos AC, Gama M, Peixoto D, Sousa-Oliveira I, Ferreira-Faria I, Zeinali M, et al. Nanocarrier-based dermopharmaceutical formulations for the topical management of atopic dermatitis. Int J Pharm. 2022;618:121656. [DOI] [PubMed]

182.

Garrós N, Bustos-Salgados P, Domènech Ò, Rodríguez-Lagunas MJ, Beirampour N, Mohammadi-Meyabadi R, et al. Baricitinib Lipid-Based Nanosystems as a Topical Alternative for Atopic Dermatitis Treatment. Pharmaceuticals (Basel). 2023;16:1–17. [DOI] [PubMed] [PMC]

183.

Campos EVR, Proença PLDF, Doretto-Silva L, Andrade-Oliveira V, Fraceto LF, de Araujo DR. Trends in nanoformulations for atopic dermatitis treatment. Expert Opin Drug Deliv. 2020;17:1615–30. [DOI] [PubMed]

184.

Brunner PM, Pavel AB, Khattri S, Leonard A, Malik K, Rose S, et al. Baseline IL-22 expression in patients with atopic dermatitis stratifies tissue responses to fezakinumab. J Allergy Clin Immunol. 2019;143:142–54. [DOI] [PubMed]

185.

Leung DYM. Evolving atopic dermatitis toward precision medicine. Ann Allergy Asthma Immunol. 2024;132:107–8. [DOI] [PubMed]

186.

Ghosh D, Ding L, Sivaprasad U, Geh E, Myers JB, Bernstein JA, et al. Multiple Transcriptome Data Analysis Reveals Biologically Relevant Atopic Dermatitis Signature Genes and Pathways. PLoS One. 2015;10:e0144316. [DOI] [PubMed] [PMC]

187.

Yamamoto-Hanada K, Kawakami E, Saito-Abe M, Sato M, Mitsubuchi H, Oda M, et al. Exploratory analysis of plasma cytokine/chemokine levels in 6-year-old children from a birth cohort study. Cytokine. 2020;130:155051. [DOI] [PubMed]

188.

Pomi FL, Papa V, Borgia F, Vaccaro M, Pioggia G, Gangemi S. Artificial Intelligence: A Snapshot of Its Application in Chronic Inflammatory and Autoimmune Skin Diseases. Life (Basel). 2024;14:516. [DOI] [PubMed] [PMC]