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治疗银屑病的新型局部治疗药物。

New Topical Therapies for Psoriasis.

机构信息

Department of Dermatology, Centro Hospitalar Universitário do Porto, Centro Hospitalar do Porto, Edifício das Consultas Externas, Ex. CICAP, Rua D. Manuel II, s/n, 4100, Porto, Portugal.

Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.

出版信息

Am J Clin Dermatol. 2022 Jan;23(1):13-24. doi: 10.1007/s40257-021-00649-w. Epub 2021 Oct 27.

DOI:10.1007/s40257-021-00649-w
PMID:34705167
Abstract

Psoriasis is a chronic immune-mediated skin disease with a significant impact on patients' quality of life. Mild-to-moderate forms of the disease usually require long-term topical treatment, but prolonged use of corticosteroids and vitamin D analogues is limited by adverse effects. With further understanding of psoriasis pathogenesis, new molecules are emerging aiming to fulfil these clinical needs. Tapinarof, an aryl hydrocarbon receptor modulator, has completed a phase III study and demonstrated good efficacy results, even in long treatment courses, with a favourable safety profile. It additionally appears to have a promising remitting effect as patients presented with an average relapsing time of over 3 months. Roflumilast, a phosphodiesterase type 4 inhibitor, also underwent a phase III study with significant lesion improvement and notable pruritus management, and with no reported side effects. Roflumilast was evaluated as an option for intertriginous areas with good outcomes in a small sample, but larger trials are required. The Janus kinase-signal transducer and activator of transcription pathway has been targeted in recent clinical investigations with promising options, currently with brepocitinib pending phase IIb results. Ongoing preclinical studies involving interleukin-2 inhibition, RNA modulators and amygdalin analogues may lead to forthcoming clinical trials. New topical drugs are successfully emerging and future research comparing them to classical options will dictate their clinical role in the treatment of psoriasis.

摘要

银屑病是一种慢性免疫介导的皮肤疾病,对患者的生活质量有重大影响。轻度至中度的疾病通常需要长期的局部治疗,但皮质类固醇和维生素 D 类似物的长期使用受到不良反应的限制。随着对银屑病发病机制的进一步了解,新的分子不断涌现,以满足这些临床需求。芳基烃受体调节剂他卡西醇已完成 III 期研究,显示出良好的疗效结果,即使在长期治疗过程中,安全性良好。此外,它似乎具有有前途的缓解作用,因为患者的平均复发时间超过 3 个月。磷酸二酯酶 4 抑制剂罗氟司特也进行了 III 期研究,显示出显著的皮损改善和明显的瘙痒管理,且无报道的副作用。罗氟司特在一项小型样本中被评估为间擦部位的选择,结果良好,但需要更大规模的试验。Janus 激酶信号转导和转录激活因子通路在最近的临床研究中得到了靶向治疗,目前有 brepocitinib 等待 IIb 期结果。正在进行的涉及白细胞介素 2 抑制、RNA 调节剂和苦杏仁苷类似物的临床前研究可能会导致即将进行的临床试验。新的局部治疗药物正在成功涌现,未来将对它们与经典药物进行比较的研究将决定它们在银屑病治疗中的临床作用。

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本文引用的文献

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Topical Application of BMS-509744, a Selective Inhibitor of Interleukin-2-Inducible T Cell Kinase, Ameliorates Imiquimod-Induced Skin Inflammation in Mice.BMS-509744,一种白细胞介素-2 诱导的 T 细胞激酶的选择性抑制剂的局部应用可改善咪喹莫特诱导的小鼠皮肤炎症。
Biol Pharm Bull. 2021 Apr 1;44(4):528-534. doi: 10.1248/bpb.b20-00850. Epub 2021 Jan 20.
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Tapinarof in the treatment of psoriasis: A review of the unique mechanism of action of a novel therapeutic aryl hydrocarbon receptor-modulating agent.他卡西醇治疗银屑病:新型芳香烃受体调节剂独特作用机制的综述。
J Am Acad Dermatol. 2021 Apr;84(4):1059-1067. doi: 10.1016/j.jaad.2020.10.085. Epub 2020 Nov 3.
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Nat Rev Dis Primers. 2025 Jun 26;11(1):45. doi: 10.1038/s41572-025-00630-5.
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A triple-targeting "nano-brake" remodeling the impaired immune microenvironment in skin lesions for psoriasis treatment.一种三重靶向“纳米刹车”重塑皮肤病变中受损的免疫微环境用于治疗银屑病。
Mater Today Bio. 2025 May 15;32:101875. doi: 10.1016/j.mtbio.2025.101875. eCollection 2025 Jun.
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PDE4 inhibitors in psoriasis therapy: current insights and future directions.银屑病治疗中的磷酸二酯酶4抑制剂:当前见解与未来方向
Inflammopharmacology. 2025 May 15. doi: 10.1007/s10787-025-01778-y.
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Scratching the Surface: A Comprehensive Guide to Understanding and Managing Vulvovaginal Itching.深入剖析:了解和管理外阴阴道瘙痒的全面指南
Am J Clin Dermatol. 2025 May;26(3):361-378. doi: 10.1007/s40257-025-00939-7. Epub 2025 Mar 25.
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Identification of neutrophil extracellular traps genes as potential biomarkers in psoriasis based on bioinformatics analysis.基于生物信息学分析鉴定中性粒细胞胞外诱捕网基因作为银屑病的潜在生物标志物。
Sci Rep. 2024 Oct 11;14(1):23848. doi: 10.1038/s41598-024-75069-x.
8
Cannabidiol Alleviates Imiquimod-Induced Psoriasis by Inhibiting JAK2-STAT3 in a Mouse Model.大麻二酚通过抑制小鼠模型中的JAK2-STAT3减轻咪喹莫特诱导的银屑病
Biomedicines. 2024 Sep 12;12(9):2084. doi: 10.3390/biomedicines12092084.
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Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies.载纳米钙泊三醇三层溶性微针贴片治疗银屑病的体外释药和体内抗银屑病活性研究。
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Novel Therapeutic Hybrid Systems Using Hydrogels and Nanotechnology: A Focus on Nanoemulgels for the Treatment of Skin Diseases.使用水凝胶和纳米技术的新型治疗混合系统:聚焦于用于治疗皮肤疾病的纳米乳凝胶
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Trial of Roflumilast Cream for Chronic Plaque Psoriasis.
罗氟司特乳膏治疗慢性斑块状银屑病的试验。
N Engl J Med. 2020 Jul 16;383(3):229-239. doi: 10.1056/NEJMoa2000073.
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A phase 2b, randomized clinical trial of tapinarof cream for the treatment of plaque psoriasis: Secondary efficacy and patient-reported outcomes.一项关于他卡西醇乳膏治疗斑块状银屑病的 2b 期、随机临床试验:次要疗效和患者报告结局。
J Am Acad Dermatol. 2021 Mar;84(3):624-631. doi: 10.1016/j.jaad.2020.04.181. Epub 2020 May 21.
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J Invest Dermatol. 2020 Dec;140(12):2359-2370.e5. doi: 10.1016/j.jid.2020.03.962. Epub 2020 Apr 18.
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Topical administration of nanocarrier miRNA-210 antisense ameliorates imiquimod-induced psoriasis-like dermatitis in mice.局部给予纳米载体 miRNA-210 反义寡核苷酸可改善咪喹莫特诱导的小鼠银屑病样皮炎。
J Dermatol. 2020 Feb;47(2):147-154. doi: 10.1111/1346-8138.15149. Epub 2019 Nov 27.
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