New progress in targeted therapy for atopic dermatitis

doi:10.3760/cma.j.issn.1007-1245.2023.24.005

Abstract

Abstract:

Atopic dermatitis is a common chronic, recurrent, and inflammatory skin disease, and seriously affects children's growth and development and adults' quality of life. Traditional therapeutic drugs often have many limitations and are not effective for patients with moderate to severe atopic dermatitis. In recent years, the emergence of new targeted drugs such as biologicals and small molecule inhibitors has brought good news to patients with moderate to severe atopic dermatitis.

Key words:

Atopic dermatitis, Biologicals, Small molecule inhibitors, Progress

摘要：

特应性皮炎（AD）是一种常见的慢性、复发性、炎症性皮肤病，严重影响患儿的成长发育和成人的生活质量。传统的治疗药物通常存在许多局限性，且往往对中重度AD患者的疗效欠佳。近年来，生物制剂和小分子抑制剂等新型靶向药物的出现，为中重度AD患者带来了福音。

关键词:

特应性皮炎, 生物制剂, 小分子抑制剂, 进展

Fang Xiangfang, Huang Yujie, Li Yanfeng, Wang Zhongyong.

New progress in targeted therapy for atopic dermatitis [J]. International Medicine and Health Guidance News, 2023, 29(24): 3546-3550.

房祥芳黄钰洁李岩峰王忠永.

特应性皮炎的靶向治疗新进展 [J]. 国际医药卫生导报, 2023, 29(24): 3546-3550.

References

[1] Silverberg JI. Public health burden and epidemiology of atopic dermatitis[J]. Dermatol Clin,2017,35(3):283-289.DOI: 10.1016/j.det.2017.02.002.
[2] Salvati L, Cosmi L, Annunziato F. From emollients to biologicals: targeting atopic dermatitis[J]. Int J Mol Sci, 2021,22(19):10381.DOI: 10.3390/ijms221910381.
[3] Drucker AM, Ellis A, Jabbar-Lopez Z,et al. Systemic immunomodulatory treatments for atopic dermatitis: protocol for a systematic review with network meta-analysis[J]. BMJ Open,2018,8(8):e023061.DOI: 10.1136/bmjopen-2018-023061.
[4] Na CH, Baghoomian W, Simpson EL. A therapeutic renaissance - emerging treatments for atopic dermatitis[J]. Acta Derm Venereol, 2020,100(12):adv00165.DOI: 10.2340/00015555-3515.
[5] Hamilton JD, Harel S, Swanson BN,et al. Dupilumab suppresses type 2 inflammatory biomarkers across multiple atopic, allergic diseases[J]. Clin Exp Allergy,2021,51(7):915-931.DOI: 10.1111/cea.13954.
[6] Le Floc'h A, Allinne J, Nagashima K,et al. Dual blockade of IL-4 and IL-13 with dupilumab, an IL-4Rα antibody, is required to broadly inhibit type 2 inflammation[J]. Allergy,2020,75(5):1188-1204.DOI: 10.1111/all.14151.
[7] 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[J]. JAMA Dermatol,2020,156(1):44-56.DOI: 10.1001/jamadermatol.2019.3336.
[8] Junttila IS. Tuning the cytokine responses: an update on interleukin (IL)-4 and IL-13 receptor complexes[J]. Front Immunol,2018,9:888.DOI: 10.3389/fimmu.2018.00888.
[9] Simpson EL, Akinlade B, Ardeleanu M. Two phase 3 trials of dupilumab versus placebo in atopic dermatitis[J]. N Engl J Med,2017,376(11):1090-1091.DOI: 10.1056/NEJMc1700366.
[10] Wang Y, Jorizzo JL. Retrospective analysis of adverse events with dupilumab reported to the united states food and drug administration[J]. J Am Acad Dermatol, 2021,84(4):1010-1014.DOI: 10.1016/j.jaad.2020.11.042.
[11] Beck LA, Thaçi D, Hamilton JD,et al. Dupilumab treatment in adults with moderate-to-severe atopic dermatitis[J]. N Engl J Med,2014,371(2):130-139.DOI: 10.1056/NEJMoa1314768.
[12] Tsoi LC, Rodriguez E, Degenhardt F,et al. Atopic dermatitis is an IL-13-dominant disease with greater molecular heterogeneity compared to psoriasis[J]. J Invest Dermatol,2019,139(7):1480-1489.DOI: 10.1016/j.jid.2018.12.018.
[13] Leyva-Castillo JM, Galand C, Mashiko S,et al. ILC2 activation by keratinocyte-derived IL-25 drives IL-13 production at sites of allergic skin inflammation[J]. J Allergy Clin Immunol, 2020,145(6):1606-1614.e4. DOI: 10.1016/j.jaci.2020.02.026.
[14] Bieber T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis[J]. Allergy,2020,75(1):54-62.DOI: 10.1111/all.13954.
[15] Zhang Y, Cheng J, Li Y,et al. The safety and efficacy of anti-IL-13 treatment with tralokinumab (CAT-354) in moderate to severe asthma: a systematic review and meta-analysis[J]. J Allergy Clin Immunol Pract,2019,7(8):2661-2671.e3.DOI: 10.1016/j.jaip.2019.05.030.
[16] Moyle M, Cevikbas F, Harden JL,et al. Understanding the immune landscape in atopic dermatitis: The era of biologics and emerging therapeutic approaches[J]. Exp Dermatol,2019,28(7):756-768.DOI: 10.1111/exd.13911.
[17] Guttman-Yassky E, Blauvelt A, Eichenfield LF,et al. Efficacy and safety of lebrikizumab, a high-affinity interleukin 13 inhibitor, in adults with moderate to severe atopic dermatitis: a phase 2b randomized clinical trial[J]. JAMA Dermatol,2020,156(4):411-420.DOI: 10.1001/jamadermatol.2020.0079.
[18] 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)[J]. Br J Dermatol,2021,184(3):437-449.DOI: 10.1111/bjd.19574.
[19] Jin M, Yoon J. From bench to clinic: the potential of therapeutic targeting of the IL-22 signaling pathway in atopic dermatitis[J]. Immune Netw,2018,18(6):e42.DOI: 10.4110/in.2018.18.e42.
[20] Ratchataswan T, Banzon TM, Thyssen JP,et al. Biologics for treatment of atopic dermatitis: current status and future prospect[J]. J Allergy Clin Immunol Pract,2021,9(3):1053-1065.DOI: 10.1016/j.jaip.2020.11.034.
[21] Gittler JK, Shemer A, Suárez-Fariñas M,et al. Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis[J]. J Allergy Clin Immunol,2012,130(6):1344-1354.DOI: 10.1016/j.jaci.2012.07.012.
[22] 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]. J Am Acad Dermatol,2018,78(5):872-881.e6.DOI: 10.1016/j.jaad.2018.01.016.
[23] Gibbs BF, Patsinakidis N, Raap U. Role of the pruritic cytokine IL-31 in autoimmune skin diseases[J]. Front Immunol,2019,10:1383.DOI: 10.3389/fimmu.2019.01383.
[24] Borgia F, Custurone P, Li Pomi F,et al. IL-31: state of the art for an inflammation-oriented interleukin[J]. Int J Mol Sci,2022,23(12):6507. DOI: 10.3390/ijms23126507.
[25] Furue M, Furue M. Interleukin-31 and pruritic skin[J]. J Clin Med,2021,28;10(9):1906.DOI: 10.3390/jcm10091906.
[26] Silverberg JI, Pinter A, Pulka G,et al. Phase 2B randomized study of nemolizumab in adults with moderate-to-severe atopic dermatitis and severe pruritus[J]. J Allergy Clin Immunol, 2020,145(1):173-182.DOI: 10.1016/j.jaci.2019.08.013.
[27] 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[J]. Br J Dermatol,2022,186(4):642-651.DOI: 10.1111/bjd.20873.
[28] Parnes JR, Sullivan JT, Chen L, et al. Pharmacokinetics, safety, and tolerability of tezepelumab (AMG 157) in healthy and atopic dermatitis adult subjects[J]. Clin Pharmacol Ther,2019,106(2):441-449.DOI: 10.1002/cpt.1401.
[29] Wang SH, Zuo YG. Thymic stromal lymphopoietin in cutaneous immune-mediated diseases[J]. Front Immunol,2021,12:698522.DOI: 10.3389/fimmu.2021.698522.
[30] Simpson EL, Parnes JR, She D,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]. J Am Acad Dermatol,2019,80(4):1013-1021.DOI: 10.1016/j.jaad.2018.11.059.
[31] Hu Y, Liu S, Liu P,et al. Clinical relevance of eosinophils, basophils, serum total IgE level, allergen-specific IgE, and clinical features in atopic dermatitis[J]. J Clin Lab Anal,2020,34(6):e23214.DOI: 10.1002/jcla.23214.
[32] Balbino B, Conde E, Marichal T,et al. Approaches to target IgE antibodies in allergic diseases[J]. Pharmacol Ther,2018,191:50-64.DOI: 10.1016/j.pharmthera.2018.05.015.
[33] Eggel A, Baravalle G, Hobi G,et al. Accelerated dissociation of IgE-FcεRI complexes by disruptive inhibitors actively desensitizes allergic effector cells[J]. J Allergy Clin Immunol,2014,133(6):1709-1719.e8.DOI: 10.1016/j.jaci.2014.02.005.
[34] Chan S, Cornelius V, Cro S,et al. Treatment effect of omalizumab on severe pediatric atopic dermatitis: the ADAPT randomized clinical trial[J]. JAMA Pediatr,2020,174(1):29-37.DOI: 10.1001/jamapediatrics.2019.4476.
[35] Di Salvo E, Ventura-Spagnolo E, Casciaro M,et al. IL-33/IL-31 axis: a potential inflammatory pathway[J]. Mediators Inflamm,2018,2018:3858032.DOI: 10.1155/2018/3858032.
[36] Chan BCL, Lam CWK, Tam LS,et al. IL33: roles in allergic inflammation and therapeutic perspectives[J]. Front Immunol,2019,10:364.DOI: 10.3389/fimmu.2019.00364.
[37] 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[J]. Sci Transl Med,2019,11(515):eaax2945.DOI: 10.1126/scitranslmed.aax2945.
[38] Puar N, Chovatiya R, Paller AS. New treatments in atopic dermatitis[J]. Ann Allergy Asthma Immunol,2021,126(1):21-31.DOI: 10.1016/j.anai.2020.08.016.
[39] Vakharia PP, Silverberg JI. New therapies for atopic dermatitis: additional treatment classes[J]. J Am Acad Dermatol,2018,78(3 Suppl 1):S76-S83.DOI: 10.1016/j.jaad.2017.12.024.
[40] Ungar B, Pavel AB, Li R,et al. Phase 2 randomized, double-blind study of IL-17 targeting with secukinumab in atopic dermatitis[J]. J Allergy Clin Immunol,2021,147(1):394-397.DOI: 10.1016/j.jaci.2020.04.055.
[41] Li H, Zuo J, Tang W. Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases[J]. Front Pharmacol,2018,9:1048.DOI: 10.3389/fphar.2018.01048.
[42] Wegesser T, Coppi A, Harper T,et al. Nonclinical genotoxicity and carcinogenicity profile of apremilast, an oral selective inhibitor of PDE4[J]. Regul Toxicol Pharmacol,2021,125:104985.DOI: 10.1016/j.yrtph.2021.104985.
[43] Luger TA, Hebert AA, Zaenglein AL,et al. Subgroup analysis of crisaborole for mild-to-moderate atopic dermatitis in children aged 2 to < 18 years[J]. Paediatr Drugs,2022,24(2):175-183.DOI: 10.1007/s40272-021-00490-y.
[44] Huang IH, Chung WH, Wu PC,et al. JAK-STAT signaling pathway in the pathogenesis of atopic dermatitis: an updated review[J]. Front Immunol,2022,13:1068260.DOI: 10.3389/fimmu.2022.1068260.
[45] Nogueira M, Torres T. Janus kinase inhibitors for the treatment of atopic dermatitis: focus on abrocitinib, baricitinib, and upadacitinib[J]. Dermatol Pract Concept,2021,11(4):e2021145.DOI: 10.5826/dpc.1104a145.
[46] Simpson EL, Sinclair R, Forman S,et al. Efficacy and safety of abrocitinib in adults and adolescents with moderate-to-severe atopic dermatitis (JADE MONO-1): a multicentre, double-blind, randomised, placebo-controlled, phase 3 trial[J]. Lancet,2020,396(10246):255-266. DOI: 10.1016/S0140-6736(20)30732-7.
[47] Papp K, Szepietowski JC, Kircik L,et al. Efficacy and safety of ruxolitinib cream for the treatment of atopic dermatitis: results from 2 phase 3, randomized, double-blind studies[J]. J Am Acad Dermatol,2021,85(4):863-872.DOI: 10.1016/j.jaad.2021.04.085.
[48] Szalus K, Trzeciak M, Nowicki RJ. JAK-STAT inhibitors in atopic dermatitis from pathogenesis to clinical trials results[J]. Microorganisms,2020,8(11):1743.DOI: 10.3390/microorganisms8111743.
[49] Tsiogka A, Kyriazopoulou M, Kontochristopoulos G,et al. The JAK/STAT pathway and its selective inhibition in the treatment of atopic dermatitis: a systematic review[J]. J Clin Med,2022,11(15):4431.DOI: 10.3390/jcm11154431.