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

Abstract

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

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

References ［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]	Sun Yuxin, Huo Siyi, Chen Jiayu, Xiong Heping, Zhu Mingfang. COVID-19-associated skin diseases: a cross-sectional survey in Changsha, China [J]. Chinese Journal of Dermatology, 2025, 58(5): 464-469.
[2]	Committee on Psoriasis, Chinese Society of Dermatology. Expert proposal on apremilast for the treatment of psoriasis （2025 edition） [J]. Chinese Journal of Dermatology, 2025, 58(5): 416-424.
[3]	He Chunxia, Jin Hongzhong . Principles, current status, challenges and perspectives in the diagnosis and treatment of critical dermatological emergencies [J]. Chinese Journal of Dermatology, 2025, 58(4): 307-314.
[4]	Dong Yi, Yan Xin, Munire·Tayier, Zhang Xingqi. Application of machine learning in dermatology [J]. Chinese Journal of Dermatology, 2025, 0(3): 20240290-e20240290.
[5]	Chinese Association of Rehabilitation Dermatology, Chinese Society of Dermatology, Photomedicine Therapeutic Equipment Group, Committee on Skin Disease and Cosmetic Dermatology, China Association of Medical Equipment. Clinical application of red, blue, and yellow light therapy in dermatology: an expert consensus statement （2025 edition） [J]. Chinese Journal of Dermatology, 2025, 58(3): 209-215.
[6]	Committee on Skin Disease and Cosmetic Dermatology, China Association of Medical Equipment. Expert consensus on the treatment of dermatoses with targeted drugs （2025 version） [J]. Chinese Journal of Dermatology, 2025, 58(2): 99-125.
[7]	Ai Fangting, Sun Zijun, Miao Guoying, Yao Chunxia. Role of calcium-sensing receptors in the pathophysiology of skin of the elderly [J]. Chinese Journal of Dermatology, 2025, 58(1): 76-79.
[8]	Zou Xianbiao, Chen Jinchun, Zeng Yue, Hao Yi. Application of ultrasonography in dermatology: progress and prospects [J]. Chinese Journal of Dermatology, 2024, 57(9): 785-790.
[9]	Zeng Yue, Shao Huihong, Lin Shiwen, Wen Rou, Zou Xianbiao. Application of a wearable teleconsultation device in diagnosis of common skin diseases [J]. Chinese Journal of Dermatology, 2024, 57(9): 797-800.
[10]	Zhang Jiaqi, Wu Fan, Han Yuqing, Liu Qi, Pan Yao. Application of multi-photon microscopy in dermatology [J]. Chinese Journal of Dermatology, 2024, 57(9): 857-862.
[11]	Hao Feng, Liu Guoyan. Application of optical coherence tomography in dermatology [J]. Chinese Journal of Dermatology, 2024, 57(9): 853-857.
[12]	Wang Chen, Xue Chenhong, Song Jinghui, Li Jianguo, Li Zhenlu, Zhang Shoumin, Li Ming, Wang Jianbo. Adalimumab for the treatment of three cases of Blau syndrome in a pedigree [J]. Chinese Journal of Dermatology, 2024, 57(6): 553-556.
[13]	Jing Ke, Li Suo, Feng Suying. Clinical and immunoserological characteristics of 26 cases of linear IgA bullous dermatosis: a retrospective analysis [J]. Chinese Journal of Dermatology, 2024, 57(6): 503-509.
[14]	Han Yan, Xu Peng, Xiang Zhi, Jiang Tingting, Ge Fengqin, Yin Yueping, Chen Xiangsheng, . Strengthening research on prevention and treatment of chronic skin diseases — population medicine research program [J]. Chinese Journal of Dermatology, 2024, 57(6): 567-569.
[15]	Liu Lyuye, Zhang Junling. Ferroptosis in common skin diseases [J]. Chinese Journal of Dermatology, 2024, 0(3): 20220783-e20220783.

Exploration of the application of apremilast in various inflammatory skin diseases

PDF

PDF (Mobile)

Knowledge

Abstract

Cite this article

share this article

References ［47］

Related Articles 15

Metrics

Comments

Recommended 10