阿普米司特在多种炎症性皮肤病应用中的探索

doi:10.35541/cjd.20240133

中华皮肤科杂志 ›› 2024, e20240133.doi: 10.35541/cjd.20240133

阿普米司特在多种炎症性皮肤病应用中的探索

韩冰王虹刘鹤松李珊山

吉林大学第一医院皮肤科，长春 130021

收稿日期:2024-03-13 修回日期:2024-10-24 发布日期:2024-12-03
通讯作者: 李珊山 E-mail:lishans@jlu.edu.cn
基金资助:
吉林省医疗卫生人才专项（JLSCZD2019-024）；吉林大学第一医院院设临床研究项目（JDYYLCYJ-20240002）

Exploration of the application of apremilast in various inflammatory skin diseases

Han Bing, Wang Hong, Liu Hesong, Li Shanshan

Department of Dermatology, the First Hospital of Jilin University, Changchun 130021, China

Received:2024-03-13 Revised:2024-10-24 Published:2024-12-03
Contact: Li Shanshan E-mail:lishans@jlu.edu.cn
Supported by:
Medical and Health Talents Project of Jilin Province （JLSCZD2019-024）; Clinical Research Projects of the First Hospital of Jilin University （JDYYLCYJ-20240002）

摘要/Abstract

摘要： 【摘要】阿普米司特是一种口服靶向磷酸二酯酶4的小分子抑制剂，可以增加环磷酸腺苷的水平，进而影响多种细胞因子的表达。该药已被美国食品药品监督管理局批准用于治疗斑块状银屑病、银屑病关节炎和白塞病的口腔溃疡。本文综述阿普米司特在多种免疫性、炎症性皮肤病中的应用。

关键词: 皮肤疾病, 磷酸二酯酶4抑制剂, 阿普米司特

Abstract: 【Abstract】 Apremilast is an orally administered small molecule inhibitor targeting phosphodiesterase-4, which can increase cyclic adenosine monophosphate levels and thereby affect the expression of various cytokines. This medicine has been approved by the U.S. Food and Drug Administration for the treatment of plaque psoriasis, psoriatic arthritis, and oral ulcers in Beh?et's disease. This review summarizes the application of apremilast in various immune and inflammatory skin diseases.

Key words: Skin diseases, Phosphodiesterase-4 inhibitors, Apremilast

韩冰王虹刘鹤松李珊山. 阿普米司特在多种炎症性皮肤病应用中的探索[J]. 中华皮肤科杂志, 2024,e20240133. doi:10.35541/cjd.20240133

Han Bing, Wang Hong, Liu Hesong, Li Shanshan. Exploration of the application of apremilast in various inflammatory skin diseases[J]. Chinese Journal of Dermatology,2024,e20240133. doi:10.35541/cjd.20240133

参考文献 47

［1］	Schick MA, Schlegel N. Clinical implication of phosphodiesterase⁃ 4⁃inhibition［J］. Int J Mol Sci, 2022,23（3）:1209. doi: 10.3390/ijms23031209.
［2］	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.
［3］	Perazzio SF, Allenspach EJ, Eklund KK, et al. Behçet disease （BD） and BD⁃like clinical phenotypes: NF⁃κB pathway in mucosal ulcerating diseases［J］. Scand J Immunol, 2020,92（5）:e12973. doi: 10.1111/sji.12973.
［4］	Hatemi G, Mahr A, Ishigatsubo Y, et al. Trial of apremilast for oral ulcers in Behçet's syndrome［J］. N Engl J Med, 2019,381（20）:1918⁃1928. doi: 10.1056/NEJMoa1816594.
［5］	Hatemi G, Melikoglu M, Tunc R, et al. Apremilast for Behçet's syndrome⁃⁃a phase 2, placebo⁃controlled study［J］. N Engl J Med, 2015,372（16）:1510⁃1518. doi: 10.1056/NEJMoa1408684.
［6］	Hatemi G, Mahr A, Takeno M, et al. Apremilast for oral ulcers associated with active Behçet's syndrome over 68 weeks: long⁃term results from a phase 3 randomised clinical trial［J］. Clin Exp Rheumatol, 2021,39 Suppl 132（5）:80⁃87. doi: 10.55563/clinexprheumatol/ra8ize.
［7］	Hatemi G, Mahr A, Takeno M, et al. Impact of apremilast on quality of life in Behçet's syndrome: analysis of the phase 3 RELIEF study［J］. RMD Open, 2022,8（2）:e002235. doi: 10. 1136/rmdopen⁃2022⁃002235.
［8］	Takeno M, Dobashi H, Tanaka Y, et al. Apremilast in a Japanese subgroup with Behçet's syndrome: results from a Phase 3, randomised, double⁃blind, placebo⁃controlled study［J］. Mod Rheumatol, 2022,32（2）:413⁃421. doi: 10.1093/mr/roab008.
［9］	Frew JW, Hawkes JE, Krueger JG. Topical, systemic and biologic therapies in hidradenitis suppurativa: pathogenic insights by examining therapeutic mechanisms［J］. Ther Adv Chronic Dis, 2019,10:204062231 9830646. doi: 10.1177/2040622319830646.
［10］	Vossen A, van Doorn M, van der Zee HH, et al. Apremilast for moderate hidradenitis suppurativa: results of a randomized controlled trial［J］. J Am Acad Dermatol, 2019,80（1）:80⁃88. doi: 10.1016/j.jaad.2018.06.046.
［11］	Aarts P, Vossen A, van der Zee HH, et al. Long⁃term treatment with apremilast in hidradenitis suppurativa: a 2⁃year follow⁃up of initial responders［J］. J Am Acad Dermatol, 2021,85（1）:258⁃260. doi: 10.1016/j.jaad.2020.08.113.
［12］	Cunningham KN, Rosmarin D. Vitiligo treatments: review of current therapeutic modalities and JAK inhibitors［J］. Am J Clin Dermatol, 2023,24（2）:165⁃186. doi: 10.1007/s40257⁃022⁃00752⁃6.
［13］	Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase⁃4 inhibitor, demonstrates anti⁃inflammatory activity in vitro and in a model of psoriasis［J］. Br J Pharmacol, 2010,159（4）:842⁃855. doi: 10.1111/j.1476⁃5381.2009.00559.x.
［14］	Majid I, Imran S, Batool S. Apremilast is effective in controlling the progression of adult vitiligo: a case series［J］. Dermatol Ther, 2019,32（4）:e12923. doi: 10.1111/dth.12923.
［15］	Khemis A, Fontas E, Moulin S, et al. Apremilast in combination with narrowband UVB in the treatment of vitiligo: a 52⁃week monocentric prospective randomized placebo⁃controlled study［J］. J Invest Dermatol, 2020,140（8）:1533⁃1537.e2. doi: 10. 1016/j.jid.2019.11.031.
［16］	Kim HJ, Singer GK, Del Duca E, et al. Combination of apremilast and narrowband ultraviolet B light in the treatment of generalized vitiligo in skin phototypes Ⅳ to Ⅵ: a randomized split⁃body pilot study［J］. J Am Acad Dermatol, 2021,85（6）:1657⁃1660. doi: 10.1016/j.jaad.2020.12.073.
［17］	Kim HJ, Del Duca E, Pavel AB, et al. Apremilast and narrowband ultraviolet B combination therapy suppresses Th17 axis and promotes melanogenesis in vitiligo skin: a randomized, split⁃body, pilot study in skin types Ⅳ⁃Ⅵ［J］. Arch Dermatol Res, 2023,315（2）:215⁃221. doi: 10.1007/s00403⁃022⁃02343⁃1.
［18］	Bitar C, Ninh T, Brag K, et al. Apremilast in recalcitrant cutaneous dermatomyositis: a nonrandomized controlled trial［J］. JAMA Dermatol, 2022,158（12）:1357⁃1366. doi: 10.1001/jamadermatol.2022.3917.
［19］	Monici MC, Aguennouz M, Mazzeo A, et al. Activation of nuclear factor⁃kappaB in inflammatory myopathies and Duchenne muscular dystrophy［J］. Neurology, 2003,60（6）:993⁃997. doi: 10.1212/01.wnl.0000049913.27181.51.
［20］	Konishi R, Tanaka R, Inoue S, et al. Evaluation of apremilast, an oral phosphodiesterase 4 inhibitor, for refractory cutaneous dermatomyositis: a phase 1b clinical trial［J］. J Dermatol, 2022,49（1）:118⁃123. doi: 10.1111/1346⁃8138.16179.
［21］	Santoro A, Majorana A, Bardellini E, et al. NF⁃kappaB expression in oral and cutaneous lichen planus［J］. J Pathol, 2003,201（3）:466⁃472. doi: 10.1002/path.1423.
［22］	Paul J, Foss CE, Hirano SA, et al. An open⁃label pilot study of apremilast for the treatment of moderate to severe lichen planus: a case series［J］. J Am Acad Dermatol, 2013,68（2）:255⁃261. doi: 10.1016/j.jaad.2012.07.014.
［23］	Viswanath V, Joshi P, Dhakne M, et al. Evaluation of the efficacy and safety of apremilast in the management of lichen planus［J］. Clin Cosmet Investig Dermatol, 2022,15:2593⁃2600. doi: 10.2147/ CCID.S390591.
［24］	Perschy L, Anzengruber F, Rappersberger K, et al. Apremilast in oral lichen planus ⁃ a multicentric, retrospective study［J］. J Dtsch Dermatol Ges, 2022,20（3）:343⁃346. doi: 10.1111/ddg.14696.
［25］	Wenzel J. Cutaneous lupus erythematosus: new insights into pathogenesis and therapeutic strategies［J］. Nat Rev Rheumatol, 2019,15（9）:519⁃532. doi: 10.1038/s41584⁃019⁃0272⁃0.
［26］	De Souza A, Strober BE, Merola JF, et al. Apremilast for discoid lupus erythematosus: results of a phase 2, open⁃label, single⁃arm, pilot study［J］. J Drugs Dermatol, 2012,11（10）:1224⁃1226.
［27］	Samrao A, Berry TM, Goreshi R, et al. A pilot study of an oral phosphodiesterase inhibitor （apremilast） for atopic dermatitis in adults［J］. Arch Dermatol, 2012,148（8）:890⁃897. doi: 10.1001/archdermatol.2012.812.
［28］	Simpson EL, Imafuku S, Poulin Y, et al. A phase 2 randomized trial of apremilast in patients with atopic dermatitis［J］. J Invest Dermatol, 2019,139（5）:1063⁃1072. doi: 10.1016/j.jid.2018. 10.043.
［29］	Mikhaylov D, Pavel A, Yao C, et al. A randomized placebo⁃controlled single⁃center pilot study of the safety and efficacy of apremilast in subjects with moderate⁃to⁃severe alopecia areata［J］. Arch Dermatol Res, 2019,311（1）:29⁃36. doi: 10.1007/s00403⁃018⁃1876⁃y.
［30］	Liu LY, King BA. Lack of efficacy of apremilast in 9 patients with severe alopecia areata［J］. J Am Acad Dermatol, 2017,77（4）:773⁃774. doi: 10.1016/j.jaad.2017.05.034.
［31］	Weber B, Radakovic S, Tanew A. Apremilast for extensive and treatment⁃resistant alopecia areata: a retrospective analysis of five patients［J］. Eur J Dermatol, 2020. doi: 10.1684/ejd.2020. 3749.
［32］	Estébanez A, Estébanez N, Martín JM, et al. Apremilast in refractory alopecia areata［J］. Int J Trichology, 2019,11（5）:213⁃215. doi: 10.4103/ijt.ijt_59_19.
［33］	Taneja N, Gupta S. Apremilast is efficacious in refractory alopecia areata［J］. J Dermatolog Treat, 2020,31（7）:727⁃729. doi: 10.1080/09546634.2019.1616046.
［34］	Thompson BJ, Furniss M, Zhao W, et al. An oral phosphodiesterase inhibitor （apremilast） for inflammatory rosacea in adults: a pilot study［J］. JAMA Dermatol, 2014,150（9）:1013⁃1014. doi: 10.1001/jamadermatol.2013.10526.
［35］	Baughman RP, Judson MA, Ingledue R, et al. Efficacy and safety of apremilast in chronic cutaneous sarcoidosis［J］. Arch Dermatol, 2012,148（2）:262⁃264. doi: 10.1001/archdermatol.2011.301.
［36］	Yoto A, Makino T, Mizawa M, et al. Two cases of Hailey⁃Hailey disease effectively treated with apremilast and a review of reported cases［J］. J Dermatol, 2021,48（12）:1945⁃1948. doi: 10. 1111/1346⁃8138.16178.
［37］	Bishnoi A, Raj D, Vinay K, et al. Refractory generalized granuloma annulare treated with oral apremilast［J］. JAMA Dermatol, 2019,155（11）:1318⁃1320. doi: 10.1001/jamadermatol. 2019.2130.
［38］	Cohen SR, Gordon SC, Lam AH, et al. Recalcitrant seborrheic dermatitis successfully treated with apremilast［J］. J Cutan Med Surg, 2020,24（1）:90⁃91. doi: 10.1177/1203475419878162.
［39］	Todberg T, Skov L, Simonsen S, et al. Efficacy of apremilast in patients with prurigo nodularis: a proof⁃of⁃concept study［J］. Acta Derm Venereol, 2020,100（8）:adv00118. doi: 10.2340/000 15555⁃3461.
［40］	Zhang L, Gebauer K. Subcorneal pustular dermatosis treated successfully with apremilast［J］. Australas J Dermatol, 2023,64（3）:e310⁃e312. doi: 10.1111/ajd.14073.
［41］	Maione V, Bettolini L, Venturuzzo A, et al. Efficacy of apremilast in a case of resistant linear IgA bullous disease［J］. Int J Dermatol, 2023,62（5）:e300⁃e302. doi: 10.1111/ijd.16548.
［42］	Adamo S, Nilsson J, Krebs A, et al. Successful treatment of SAPHO syndrome with apremilast［J］. Br J Dermatol, 2018,179（4）:959⁃962. doi: 10.1111/bjd.16071.
［43］	Vernero M, Ribaldone DG, Cariti C, et al. Dual⁃targeted therapy with apremilast and vedolizumab in pyoderma gangrenosum associated with Crohn's disease［J］. J Dermatol, 2020,47（6）:e216⁃e217. doi: 10.1111/1346⁃8138.15283.
［44］	Sánchez⁃Velázquez A, Falkenhain⁃López D, Arroyo⁃Andrés J, et al. Apremilast: a novel adjuvant treatment for refractory isotretinoin⁃induced acne fulminans［J］. Dermatol Ther, 2022,35（8）:e15637. doi: 10.1111/dth.15637.
［45］	Krase IZ, Cavanaugh K, Curiel⁃Lewandrowski C. Treatment of refractory pityriasis rubra pilaris with novel phosphodiesterase 4 （PDE4） inhibitor apremilast［J］. JAMA Dermatol, 2016,152（3）:348⁃350. doi: 10.1001/jamadermatol.2015.3405.
［46］	Meier K, Holstein J, Solimani F, et al. Case report: apremilast for therapy⁃resistant pemphigus vulgaris［J］. Front Immunol, 2020,11:588315. doi: 10.3389/fimmu.2020.588315.
［47］	Abril⁃Pérez C, Palacios⁃Diaz RD, Navarro⁃Mira MÁ, et al. Successful treatment of erythema nodosum leprosum with apremilast［J］. Dermatol Ther, 2022,35（3）:e15258. doi: 10.1111/ dth.15258.

[1]	艾芳婷孙紫君苗国英姚春霞. 钙敏感受体在老年皮肤病理生理中的作用研究进展[J]. 中华皮肤科杂志, 2025, 58(1): 76-79.
[2]	邹先彪陈锦纯曾悦郝轶. [开放获取] 超声检查在皮肤科的应用前景[J]. 中华皮肤科杂志, 2024, 57(9): 785-790.
[3]	曾悦邵惠红林诗雯温柔邹先彪. 可穿戴远程会诊设备在常见皮肤病诊断中的应用[J]. 中华皮肤科杂志, 2024, 57(9): 797-800.
[4]	郝峰刘国艳. [开放获取] 光学相干断层扫描技术在皮肤科的应用进展[J]. 中华皮肤科杂志, 2024, 57(9): 853-857.
[5]	张嘉琪吴凡韩雨晴刘琦盘瑶. 多光子显微镜在皮肤科中的应用[J]. 中华皮肤科杂志, 2024, 57(9): 857-862.
[6]	王晨薛晨红宋静卉李建国李振鲁张守民李明王建波. 阿达木单抗治疗Blau综合征1家系3例[J]. 中华皮肤科杂志, 2024, 57(6): 553-556.
[7]	荆可李锁冯素英. 线状IgA大疱性皮病26例临床及免疫血清学特征回顾分析[J]. 中华皮肤科杂志, 2024, 57(6): 503-509.
[8]	韩燕徐鹏向志姜婷婷葛凤琴尹跃平陈祥生. [开放获取] 加强慢性皮肤病的防治研究——群医学研究计划[J]. 中华皮肤科杂志, 2024, 57(6): 567-569.
[9]	姜兆婷坚哲. 人工合成仿生纳米聚多巴胺黑色素在皮肤科的应用与展望[J]. 中华皮肤科杂志, 2024, 0(3): 20220567-e20220567.
[10]	朱婷婷张学军. 阿普米司特在斑块状银屑病治疗中的研究进展[J]. 中华皮肤科杂志, 2024, 0(3): 20230448-e20230448.
[11]	郝丹王怡怡肖月闫薇李薇. [开放获取] 特殊部位银屑病系统治疗临床研究进展[J]. 中华皮肤科杂志, 2024, 0(3): 20230190-e20230190.
[12]	洪永镇王倩梁俊琴. 二代测序技术在非遗传性皮肤病领域中的运用[J]. 中华皮肤科杂志, 2024, 0(3): 20220436-e20220436.
[13]	刘绿野张峻岭. 铁死亡在常见皮肤病中的研究进展[J]. 中华皮肤科杂志, 2024, 0(3): 20220783-e20220783.
[14]	高金平张学军. 巴瑞替尼在皮肤科的临床应用进展[J]. 中华皮肤科杂志, 2024, 0(3): 20230528-e20230528.
[15]	郭蕾曹春艳方晓雅冯素英. 自身免疫性大疱病患者创面感染多重耐药菌现况及危险因素分析[J]. 中华皮肤科杂志, 2024, 57(2): 155-160.

阿普米司特在多种炎症性皮肤病应用中的探索

Exploration of the application of apremilast in various inflammatory skin diseases

PDF

PDF (Mobile)

可视化

摘要/Abstract

引用本文

使用本文

参考文献 47

相关文章 15

Metrics

本文评价

推荐阅读 10