Janus激酶-信号转导及转录激活因子信号通路抑制剂在白癜风治疗中的新进展

doi:10.35541/cjd.20230173

Abstract

Abstract: 【Abstract】 In recent years, with the in-depth research on the pathogenesis of vitiligo, the Janus kinase （JAK）-signal transducer and activator of transcription （STAT） pathway has attracted more and more attention. This review summarizes the role of the JAK-STAT signaling pathway in the development of vitiligo, as well as JAK-STAT inhibitors that are currently being studied or have been used in the treatment of vitiligo.

Key words: Vitiligo, Janus kinases, STAT transcription factors, JAK-STAT inhibitor, Treatment

Guliziba·Tuersun, Qu Yuanyuan. New advances in the treatment of vitiligo with JAK-STAT inhibitors[J]. Chinese Journal of Dermatology, 2024, 57(1): 71-75.doi:10.35541/cjd.20230173

References ［40］

［1］	Ciechanowicz P, Rakowska A, Sikora M, et al. JAK⁃inhibitors in dermatology: current evidence and future applications［J］. J Dermatolog Treat, 2019,30（7）:648⁃658. doi: 10.1080/09546634. 2018.1546043.
［2］	Rosmarin D, Passeron T, Pandya AG, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo［J］. N Engl J Med, 2022,387（16）:1445⁃1455. doi: 10.1056/NEJMoa 2118828.
［3］	Zhang J, Qi F, Dong J, et al. Application of baricitinib in dermatology［J］. J Inflamm Res, 2022,15:1935⁃1941. doi: 10. 2147/JIR.S356316.
［4］	Komnitski M, Komnitski A, Komnitski Junior A, et al. Partial repigmentation of vitiligo with tofacitinib, without exposure to ultraviolet radiation［J］. An Bras Dermatol, 2020,95（4）:473⁃476. doi: 10.1016/j.abd.2019.08.032.
［5］	Olamiju B, Craiglow BG. Tofacitinib cream plus narrowband ultraviolet B phototherapy for segmental vitiligo in a child［J］. Pediatr Dermatol, 2020,37（4）:754⁃755. doi: 10.1111/pde.14159.
［6］	Qi F, Liu F, Gao L. Janus kinase inhibitors in the treatment of vitiligo: a review［J］. Front Immunol, 2021,12:790125. doi: 10. 3389/fimmu.2021.790125.
［7］	Favoino E, Prete M, Catacchio G, et al. Working and safety profiles of JAK/STAT signaling inhibitors. Are these small molecules also smart?［J］. Autoimmun Rev, 2021,20（3）:102750. doi: 10.1016/j.autrev.2021.102750.
［8］	Niu C, Xie H, Aisa HA. Janus kinase inhibitors: a review of their application in the vitiligo［J］. Mini Rev Med Chem, 2021,21（20）:3203⁃3218. doi: 10.2174/1389557521666210325120233.
［9］	Sheikh A, Rafique W, Owais R, et al. FDA approves ruxolitinib （opzelura） for vitiligo therapy: a breakthrough in the field of dermatology［J］. Ann Med Surg （Lond）, 2022,81:104499. doi: 10.1016/j.amsu.2022.104499.
［10］	Pandya AG, Harris JE, Lebwohl M, et al. Addition of narrow⁃band UVB phototherapy to ruxolitinib cream in patients with vitiligo［J］. J Invest Dermatol, 2022,142（12）:3352⁃3355. doi: 10.1016/j.jid.2022.05.1093.
［11］	Craiglow BG, King BA. Tofacitinib citrate for the treatment of vitiligo: a pathogenesis⁃directed therapy［J］. JAMA Dermatol, 2015,151（10）:1110⁃1112. doi: 10.1001/jamadermatol.2015.1520.
［12］	Moore AY, Maberry S. 26966 Tofacitinib treats unresponsive vitiligo and elevated thyroid peroxidase antibodies［J］. J Am Acad Dermatol, 2021,85（3 suppl）:AB124. doi:10.1016/j.jaad. 2021.06.515.
［13］	Scheinberg M, Ferreira SB, Santos D. Tofacitinib⁃induced remission simultaneously in arthritis and vitiligo［J］. Eur J Rheumatol, 2021,8（1）:55⁃56. doi: 10.5152/eurjrheum.2020. 20007.
［14］	Liu LY, Strassner JP, Refat MA, et al. Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure［J］. J Am Acad Dermatol, 2017,77（4）:675⁃682.e1. doi: 10.1016/j.jaad.2017.05.043.
［15］	Liang J, Yu Y, Li C, et al. Tofacitinib combined with melanocyte protector α⁃MSH to treat vitiligo through dextran based hydrogel microneedles［J］. Carbohydr Polym, 2023,305:120549. doi: 10.1016/j.carbpol.2023.120549.
［16］	Yagi K, Ishida Y, Otsuka A, et al. Two cases of vitiligo vulgaris treated with topical Janus kinase inhibitor delgocitinib［J］. Australas J Dermatol, 2021,62（3）:433⁃434. doi: 10.1111/ajd. 13572.
［17］	Jin R, Zhou M, Lin F, et al. Pathogenic Th2 cytokine profile skewing by IFN⁃γ⁃responding vitiligo fibroblasts via CCL2/CCL8［J］. Cells, 2023,12（2）:217. doi: 10.3390/cells12020217.
［18］	Dong J, Huang X, Ma LP, et al. Baricitinib is effective in treating progressing vitiligo in vivo and in vitro［J］. Dose Response, 2022,20（2）:15593258 221105370. doi: 10.1177/15593258221105370.
［19］	Mumford BP, Gibson A, Chong AH. Repigmentation of vitiligo with oral baricitinib［J］. Australas J Dermatol, 2020,61（4）:374⁃376. doi: 10.1111/ajd.13348.
［20］	李子航, 王睿, 张昕. 巴瑞替尼治疗进展期白癜风疗效分析［J］. 中国麻风皮肤病杂志, 2023,39（2）:102⁃105. doi: 10.12144/ zgmfskin202302102.
［21］	Aclaris Therapeutics, Inc. A study of ATI⁃50002 topical solution for the treatment of vitiligo［EB/OL］. （2020⁃11⁃30）［2023⁃11⁃28］. https://clinicaltrials.gov/ct2/show/NCT03468855.
［22］	Su X, Luo R, Ruan S, et al. Efficacy and tolerability of oral upadacitinib monotherapy in patients with recalcitrant vitiligo［J］. J Am Acad Dermatol, 2023,89（6）:1257⁃1259. doi: 10.1016/j.jaad.2023.07.1016.
［23］	Pan T, Mu Y, Shi X, et al. Concurrent vitiligo and atopic dermatitis successfully treated with upadacitinib: a case report［J］. J Dermatolog Treat, 2023,34（1）:2200873. doi: 10.1080/09546634.2023.2200873.
［24］	Ezzedine K, Peeva E, Yamaguchi Y, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial［J］. J Am Acad Dermatol, 2023,88（2）:395⁃403. doi: 10.1016/j.jaad.2022.11.005.
［25］	Guttman⁃Yassky E, Del Duca E, Da Rosa JC, et al. Improvements in immune/melanocyte biomarkers with JAK3/TEC family kinase inhibitor ritlecitinib in vitiligo［J］. J Allergy Clin Immunol, 2023:S0091⁃6749（23）01202⁃01202. doi: 10.1016/j.jaci.2023. 09.021.
［26］	Huang X, Ding X. Jak inhibitors in vitiligo: a meta analysis［J/OL］. Chin Med J （Engl）, 2023,136（23）:2897⁃2898. doi: 10.1097/CM9. 0000000000002581.
［27］	Phan K, Phan S, Shumack S, et al. Repigmentation in vitiligo using janus kinase （JAK） inhibitors with phototherapy: systematic review and meta⁃analysis［J］. J Dermatolog Treat, 2022,33（1）:173⁃177. doi: 10.1080/09546634.2020.1735615.
［28］	Narla S, Oska S, Lyons AB, et al. Association of myalgias with compounded topical Janus kinase inhibitor use in vitiligo［J］. JAAD Case Rep, 2020,6（7）:637⁃639. doi: 10.1016/j.jdcr.2020. 05.002.
［29］	Ytterberg SR, Bhatt DL, Connell CA. Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis. reply［J］. N Engl J Med, 2022,386（18）:1768. doi: 10.1056/NEJMc2202778.
［30］	Sardana K, Muddebihal A, Khurana A. JAK inhibitors in vitiligo: what they hit and what they miss⁃an immunopathogenesis based exposition of existing evidence［J］. Expert Rev Clin Pharmacol, 2023:1⁃7. doi: 10.1080/17512433.2023.2285011.
［31］	Noël M, Gagné C, Bergeron J, et al. Positive pleiotropic effects of HMG⁃CoA reductase inhibitor on vitiligo［J］. Lipids Health Dis, 2004,3:7. doi: 10.1186/1476⁃511X⁃3⁃7.
［32］	Shaker E, Allam SH, Mabrouk MM, et al. Simvastatin and non⁃segmental vitiligo: a new potential treatment option?［J］. Dermatol Ther, 2022,35（12）:e15969. doi: 10.1111/dth.15969.
［33］	Zhang S, Zdravković TP, Wang T, et al. Efficacy and safety of oral simvastatin in the treatment of patients with vitiligo［J］. J Investig Med, 2021,69（2）:393⁃396. doi: 10.1136/jim⁃2020⁃001390.
［34］	Verma D, Hussain K, Namiq KS, et al. Vitiligo: the association with metabolic syndrome and the role of simvastatin as an immunomodulator［J］. Cureus, 2021,13（3）:e14029. doi: 10.7759/ cureus.14029.
［35］	Agarwal P, Rashighi M, Essien KI, et al. Simvastatin prevents and reverses depigmentation in a mouse model of vitiligo［J］. J Invest Dermatol, 2015,135（4）:1080⁃1088. doi: 10.1038/jid.2014. 529.
［36］	Vanderweil SG, Amano S, Ko WC, et al. A double⁃blind, placebo⁃controlled, phase⁃Ⅱ clinical trial to evaluate oral simvastatin as a treatment for vitiligo［J］. J Am Acad Dermatol, 2017,76（1）:150⁃151.e3. doi: 10.1016/j.jaad.2016.06.015.
［37］	Chang Y, Li S, Guo W, et al. Simvastatin protects human melanocytes from H2O2⁃induced oxidative stress by activating Nrf2［J］. J Invest Dermatol, 2017,137（6）:1286⁃1296. doi: 10. 1016/j.jid.2017.01.020.
［38］	Jian Z, Tang L, Yi X, et al. Aspirin induces Nrf2⁃mediated transcriptional activation of haem oxygenase⁃1 in protection of human melanocytes from H2O2⁃induced oxidative stress［J］. J Cell Mol Med, 2016,20（7）:1307⁃1318. doi: 10.1111/jcmm.12812.
［39］	Rodrigues JL, Rodrigues LR. Biosynthesis and heterologous production of furanocoumarins: perspectives and current challenges［J］. Nat Prod Rep, 2021,38（5）:869⁃879. doi: 10. 1039/d0np00074d.
［40］	Niu C, Zang D, Aisa HA. Study of novel furocoumarin derivatives on anti⁃vitiligo activity, molecular docking and mechanism of action［J］. Int J Mol Sci, 2022,23（14）:7959. doi: 10.3390/ijms23147959.

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[2]	. [J]. Chinese Journal of Dermatology, 2005, 38(12): 762 -763 .
[3]	李芃, 涂亚庭, 陈小强. [J]. Chinese Journal of Dermatology, 2005, 38(12): 764 .
[4]	. [J]. Chinese Journal of Dermatology, 2005, 38(12): 774 .
[5]	李靖华, 周晓鸿. [J]. Chinese Journal of Dermatology, 2005, 38(12): 775 .
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[10]	. [J]. Chinese Journal of Dermatology, 2005, 38(11): 705 .

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New advances in the treatment of vitiligo with JAK-STAT inhibitors

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