系统小分子药物和生物制剂治疗斑秃的临床研究进展

doi:10.35541/cjd.20240247

Abstract

Abstract: 【Abstract】 Alopecia areata （AA） is an autoimmune-mediated, hair follicle-targeting, inflammatory, non-scarring hair loss. The treatment of severe AA has long been a focus and challenge. Currently, novel therapeutic agents, such as Janus kinase （JAK） inhibitors, have been increasingly employed in the treatment of severe AA. This review provides an overview of new small-molecule targeted drugs and biologics for AA.

Key words: Alopecia areata, Janus kinase inhibitors, Molecular targeted therapy, Biologics

Li Xiangqian, Zhang Jianzhong, Zhou Cheng. Advances in the clinical research on systemic small-molecule drugs and biologics for the treatment of alopecia areata[J]. Chinese Journal of Dermatology,2025,e20240247. doi:10.35541/cjd.20240247

References ［42］

［1］	Zhou C, Li X, Wang C, et al. Alopecia areata: an update on etiopathogenesis, diagnosis, and management［J］. Clin Rev Allergy Immunol, 2021,61（3）:403⁃423. doi: 10.1007/s12016⁃021⁃08883⁃0.
［2］	Fatani M, Alkhalifah A, Alruwaili A, et al. Diagnosis and management of alopecia areata: a Saudi expert consensus statement （2023）［J］. Dermatol Ther （Heidelb）, 2023,13（10）:2129⁃2151. doi: 10.1007/s13555⁃023⁃00991⁃3.
［3］	Harel S, Higgins CA, Cerise JE, et al. Pharmacologic inhibition of JAK⁃STAT signaling promotes hair growth［J］. Sci Adv, 2015,1（9）:e1500973. doi: 10.1126/sciadv.1500973.
［4］	King B, Ohyama M, Kwon O, et al. Two phase 3 trials of baricitinib for alopecia areata［J］. N Engl J Med, 2022,386（18）:1687⁃1699. doi: 10.1056/NEJMoa2110343.
［5］	Senna M, Mostaghimi A, Ohyama M, et al. Long⁃term efficacy and safety of baricitinib in patients with severe alopecia areata: 104⁃week results from BRAVE⁃AA1 and BRAVE⁃AA2［J］. J Eur Acad Dermatol Venereol, 2024,38（3）:583⁃593. doi: 10. 1111/jdv.19665.
［6］	King B, Guttman⁃Yassky E, Peeva E, et al. A phase 2a randomized, placebo⁃controlled study to evaluate the efficacy and safety of the oral Janus kinase inhibitors ritlecitinib and brepocitinib in alopecia areata: 24⁃week results［J］. J Am Acad Dermatol, 2021,85（2）:379⁃387. doi: 10.1016/j.jaad.2021.03.050.
［7］	King B, Zhang X, Harcha WG, et al. Efficacy and safety of ritlecitinib in adults and adolescents with alopecia areata: a randomised, double⁃blind, multicentre, phase 2b⁃3 trial［J］. Lancet, 2023,401（10387）:1518⁃1529. doi: 10.1016/S0140⁃6736（23）00222⁃2.
［8］	Peeva E, Guttman⁃Yassky E, Banerjee A, et al. Maintenance, withdrawal, and re⁃treatment with ritlecitinib and brepocitinib in patients with alopecia areata in a single⁃blind extension of a phase 2a randomized clinical trial［J］. J Am Acad Dermatol, 2022,87（2）:390⁃393. doi: 10.1016/j.jaad.2021.12.008.
［9］	King B, Soung J, Tziotzios C, et al. Integrated safety analysis of ritlecitinib, an oral JAK3/TEC family kinase inhibitor, for the treatment of alopecia areata from the ALLEGRO clinical trial program［J］. Am J Clin Dermatol, 2024,25（2）:299⁃314. doi: 10.1007/s40257⁃024⁃00846⁃3.
［10］	Guo L, Feng S, Sun B, et al. Benefit and risk profile of tofacitinib for the treatment of alopecia areata: a systemic review and meta⁃analysis［J］. J Eur Acad Dermatol Venereol, 2020,34（1）:192⁃201. doi: 10.1111/jdv.15937.
［11］	King B, Mesinkovska N, Mirmirani P, et al. Phase 2 randomized, dose⁃ranging trial of CTP⁃543, a selective Janus kinase inhibitor, in moderate⁃to⁃severe alopecia areata［J］. J Am Acad Dermatol, 2022,87（2）:306⁃313. doi: 10.1016/j.jaad.2022.03.045.
［12］	Zhou C, Yang X, Yang B, et al. A randomized, double⁃blind, placebo⁃controlled phaseⅡ study to evaluate the efficacy and safety of ivarmacitinib （SHR0302） in adult patients with moderate⁃to⁃severe alopecia areata［J］. J Am Acad Dermatol, 2023,89（5）:911⁃919. doi: 10.1016/j.jaad.2023.02.063.
［13］	Zhang Y, Zhou H, Jiang Z, et al. Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor⁃naïve patients with myelofibrosis: results of a phaseⅡ trial［J］. Am J Hematol, 2022,97（12）:1510⁃1519. doi: 10.1002/ajh.26709.
［14］	Wrobleski ST, Moslin R, Lin S, et al. Highly selective inhibition of tyrosine kinase 2 （TYK2） for the treatment of autoimmune diseases: discovery of the allosteric inhibitor BMS⁃986165［J］. J Med Chem, 2019,62（20）:8973⁃8995. doi: 10.1021/acs.jmedchem.9b00444.
［15］	Oliel S, Moussa S, Stanciu M, et al. Rapid hair regrowth in an alopecia universalis patient with deucravacitinib: a case report［J］. SAGE Open Med Case Rep, 2023,11:2050313X231213135. doi: 10.1177/2050313X231213135.
［16］	Wei D, Chen Y, Shen Y, et al. Efficacy and safety of different JAK inhibitors in the treatment of alopecia areata: a network meta⁃analysis［J］. Front Immunol, 2023,14:1152513. doi: 10. 3389/fimmu.2023.1152513.
［17］	Papierzewska M, Waśkiel⁃Burnat A, Rudnicka L. Safety of Janus kinase inhibitors in patients with alopecia areata: a systematic review［J］. Clin Drug Investig, 2023,43（5）:325⁃334. doi: 10. 1007/s40261⁃023⁃01260⁃z.
［18］	Chen Y, Zhu H, Shen Y, et al. Efficacy and safety of JAK inhibitors in the treatment of alopecia areata in children: a systematic review and meta⁃analysis［J］. J Dermatolog Treat, 2022,33（8）:3143⁃3149. doi: 10.1080/09546634.2022.2133956.
［19］	Sechi A, Song J, Dell'Antonia M, et al. Adverse events in patients treated with Jak⁃inhibitors for alopecia areata: a systematic review［J］. J Eur Acad Dermatol Venereol, 2023. doi: 10.1111/jdv.19090.
［20］	Cohen SB, Tanaka Y, Mariette X, et al. Long⁃term safety of tofacitinib up to 9.5 years: a comprehensive integrated analysis of the rheumatoid arthritis clinical development programme［J］. RMD Open, 2020,6（3）:e001395. doi: 10.1136/rmdopen⁃2020⁃001395.
［21］	Álvaro⁃Gracia JM, García⁃Llorente JF, Valderrama M, et al. Update on the safety profile of tofacitinib in rheumatoid arthritis from clinical trials to real⁃world studies: a narrative review［J］. Rheumatol Ther, 2021,8（1）:17⁃40. doi: 10.1007/s40744⁃020⁃00258⁃9.
［22］	Corbella⁃Bagot L, Riquelme⁃McLoughlin C, Morgado⁃Carrasco D. Long⁃term safety profile and off⁃label use of JAK inhibitors in dermatological disorders［J］. Actas Dermosifiliogr, 2023,114（9）:T784⁃T801. doi: 10.1016/j.ad.2023.08.002.
［23］	Guidelli GM, Viapiana O, Luciano N, et al. Efficacy and safety of baricitinib in 446 patients with rheumatoid arthritis: a real⁃life multicentre study［J］. Clin Exp Rheumatol, 2021,39（4）:868⁃873. doi: 10.55563/clinexprheumatol/pudtpo.
［24］	Ytterberg SR, Bhatt DL, Mikuls TR, et al. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis［J］. N Engl J Med, 2022,386（4）:316⁃326. doi: 10.1056/NEJMoa2109927.
［25］	Rudnicka L, Arenbergerova M, Grimalt R, et al. European expert consensus statement on the systemic treatment of alopecia areata［J］. J Eur Acad Dermatol Venereol, 2024,38（4）:687⁃694. doi: 10.1111/jdv.19768.
［26］	Barati Sedeh F, Michaelsdóttir TE, Henning M, et al. Comparative efficacy and safety of janus kinase inhibitors used in alopecia areata: a systematic review and meta⁃analysis［J］. Acta Derm Venereol, 2023,103:adv00855. doi: 10.2340/actadv.v103.4536.
［27］	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］. J Am Acad Dermatol, 2021,84（1）:139⁃147. doi: 10.1016/j.jaad.2020.08.051.
［28］	Czarnowicki T, He HY, Wen HC, et al. Alopecia areata is characterized by expansion of circulating Th2/Tc2/Th22, within the skin⁃homing and systemic T⁃cell populations［J］. Allergy, 2018,73（3）:713⁃723. doi: 10.1111/all.13346.
［29］	Guttman⁃Yassky E, Renert⁃Yuval Y, Bares J, et al. Phase 2a randomized clinical trial of dupilumab （anti⁃IL⁃4Rα） for alopecia areata patients［J］. Allergy, 2022,77（3）:897⁃906. doi: 10.1111/all.15071.
［30］	章星琪. 国内外斑秃诊疗共识、指南的解读与启示［J］. 皮肤性病诊疗学杂志, 2021,28（6）:431⁃436. doi: 10.3969/j.issn. 1674⁃8468.2021.06.001.
［31］	Sachdeva M, Witol A, Mufti A, et al. Alopecia areata related paradoxical reactions in patients on dupilumab therapy: a systematic review［J］. J Cutan Med Surg, 2021,25（4）:451⁃452. doi: 10.1177/1203475421995186.
［32］	Napolitano M, Fabbrocini G, Patruno C. Dupilumab⁃associated cutaneous adverse events among adult patients with atopic dermatitis: a retrospective study［J］. J Dermatol, 2023,50（7）:880⁃887. doi: 10.1111/1346⁃8138.16764.
［33］	Saadoun D, Rosenzwajg M, Joly F, et al. Regulatory T⁃cell responses to low⁃dose interleukin⁃2 in HCV⁃induced vasculitis［J］. N Engl J Med, 2011,365（22）:2067⁃2077. doi: 10.1056/NEJMoa1105143.
［34］	Sharabi A, Tsokos MG, Ding Y, et al. Regulatory T cells in the treatment of disease［J］. Nat Rev Drug Discov, 2018,17（11）:823⁃844. doi: 10.1038/nrd.2018.148.
［35］	Boardman DA, Levings MK. Emerging strategies for treating autoimmune disorders with genetically modified Treg cells［J］. J Allergy Clin Immunol, 2022,149（1）:1⁃11. doi: 10.1016/j.jaci. 2021.11.007.
［36］	Le Duff F, Bouaziz JD, Fontas E, et al. Low⁃dose IL⁃2 for treating moderate to severe alopecia areata: a 52⁃week multicenter prospective placebo⁃controlled study assessing its impact on t regulatory cell and NK cell populations［J］. J Invest Dermatol, 2021,141（4）:933⁃936.e6. doi: 10.1016/j.jid.2020.08.015.
［37］	Castela E, Le Duff F, Butori C, et al. Effects of low⁃dose recombinant interleukin 2 to promote T⁃regulatory cells in alopecia areata［J］. JAMA Dermatol, 2014,150（7）:748⁃751. doi: 10.1001/jamadermatol.2014.504.
［38］	Dahabreh D, Jung S, Renert⁃Yuval Y, et al. Alopecia areata: current treatments and new directions［J］. Am J Clin Dermatol, 2023,24（6）:895⁃912. doi: 10.1007/s40257⁃023⁃00808⁃1.
［39］	Ramírez⁃Marín HA, Tosti A. Emerging drugs for the treatment of alopecia areata［J］. Expert Opin Emerg Drugs, 2022,27（4）:379⁃387. doi: 10.1080/14728214.2022.2149735.
［40］	Passeron T, King B, Seneschal J, et al. Inhibition of T⁃cell activity in alopecia areata: recent developments and new directions［J］. Front Immunol, 2023,14:1243556. doi: 10.3389/fimmu.2023.1243556.
［41］	Stepanovska B, Huwiler A. Targeting the S1P receptor signaling pathways as a promising approach for treatment of autoimmune and inflammatory diseases［J］. Pharmacol Res, 2020,154:104170. doi: 10.1016/j.phrs.2019.02.009.
［42］	Cranwell WC, Lai VW, Photiou L, et al. Treatment of alopecia areata: an Australian expert consensus statement［J］. Australas J Dermatol, 2019,60（2）:163⁃170. doi: 10.1111/ajd.12941.

[1]	Sui Changlin, Chang Xiao, Zhao Qi, Zhu Wei. Psoriasis induced by anti-tumor targeted therapy and immunotherapy [J]. Chinese Journal of Dermatology, 2024, 57(6): 570-574.
[2]	Yan Rufan, Liao Jieyue, Guo Ziyu, Yao Nan, Zhou Wenyu, Luo Shuaihantian, Zhang Guiying, Zhao Ming. Pathogenesis and targeted therapy of pemphigus [J]. Chinese Journal of Dermatology, 2024, 57(4): 374-378.
[3]	Gao Jinping, Zhang Xuejun, . Clinical application of baricitinib in dermatology [J]. Chinese Journal of Dermatology, 2024, 0(3): 20230528-e20230528.
[4]	Wei Ran, Li Qinfeng. Novel targeted drugs for the treatment of pediatric alopecia areata [J]. Chinese Journal of Dermatology, 2024, 0(3): 20230660-e20230660.
[5]	China Dermatologist Association, Chinese Society of Dermatology, Dermatology Branch of China International Exchange and Promotive Association for Medical and Health Care, State Key Laboratory of Complex Severe and Rare Diseases, National Clinical Research Center for Dermatologic and Immunologic Diseases. Expert consensus on the application and management of therapeutic drugs for atopic dermatitis （2024） [J]. Chinese Journal of Dermatology, 2024, 57(2): 97-108.
[6]	Pan Ting, Mu Yuzhu, Shi Xin, Chen Lingling. Upadacitinib for the successful treatment of an adolescent with severe alopecia areata complicated by atopic dermatitis [J]. Chinese Journal of Dermatology, 2024, 57(12): 1138-1140.
[7]	Wang Gang. Challenges and strategies for the treatment of bullous pemphigoid [J]. Chinese Journal of Dermatology, 2024, 57(10): 887-890.
[8]	Liu Yuanxiang, Liang Yuan, Zhao Xinrong, Sun Yujuan, Ma Lin, Xu Zigang. Janus kinase inhibitors for the treatment of five children with severe alopecia areata [J]. Chinese Journal of Dermatology, 2023, 56(9): 849-852.
[9]	Wang Yuqian, Qiao Jianjun, Fang Hong. Comparison of the latest Chinese and international guidelines/consensus on diagnosis and treatment of alopecia areata [J]. Chinese Journal of Dermatology, 2023, 56(9): 885-888.
[10]	Song Zhiqiang, Chen Qiquan, Ge Lan. Insights into the progress in targeted therapy of atopic dermatitis from the perspective of its pathogenesis [J]. Chinese Journal of Dermatology, 2023, 56(8): 718-723.
[11]	Sun Jiayi, Song Xiuzu. Autophagy in hair physiology and pathology [J]. Chinese Journal of Dermatology, 2023, 0(2): 20220036-e20220036.
[12]	Wang Guanyu, Wang Yimeng, Li Weiwei, Zhang Chunlei. Novel non-chemotherapeutic treatment options for relapsed/refractory cutaneous T-cell lymphomas [J]. Chinese Journal of Dermatology, 2023, 56(12): 1170-1173.
[13]	Cao Meng, Hong Anlan, Wang Yan, Fang Fang. Clinical progress in pediatric melanoma [J]. Chinese Journal of Dermatology, 2023, 56(11): 1074-1078.
[14]	Zhao Peng, Qin Xiaowei, Qin Junxia, Liang Lili, Zhang Xinzhong, Gao Jie. Regulatory effect of interleukin-18 on natural killer cell activity in patients with alopecia areata [J]. Chinese Journal of Dermatology, 2022, 55(9): 778-783.
[15]	Yu Chen, Wang Gang. Small-molecule targeted agents: new choices for the treatment of psoriasis [J]. Chinese Journal of Dermatology, 2022, 55(9): 747-751.

Advances in the clinical research on systemic small-molecule drugs and biologics for the treatment of alopecia areata

PDF

PDF (Mobile)

Knowledge

Abstract

Cite this article

share this article

References ［42］

Related Articles 15

Metrics

Comments

Recommended 10