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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

PDE4 inhibitors in psoriasis therapy: current insights and future directions.

作者信息

Sharma Amit, Pandoh Niyati, Dayal Keerti, Raj Aditya, Kaur Kirandeep, Sandhu Navjot Kaur, Rai Vineet Kumar, Thakur Shubham, Kurmi Balak Das

机构信息

IKG Punjab Technical University, Kapurthala, Punjab, 144603, India.

Department of Pharmaceutics, ISF College of Pharmacy, GT Road, Moga, Punjab, 142001, India.

出版信息

Inflammopharmacology. 2025 May 15. doi: 10.1007/s10787-025-01778-y.


DOI:10.1007/s10787-025-01778-y
PMID:40374992
Abstract

The chronic autoimmune disease known as psoriasis creates major life-quality problems for affected patients. The disease evolves through genetic and environmental triggers that trigger continuous keratinocyte multiplication with persistent inflammation. Research into psoriasis treatment now emphasizes phosphodiesterase-4 (PDE4) inhibitors because they manage cyclic adenosine monophosphate (cAMP) signaling to reduce inflammatory cytokine production. This review examines the PDE4 inhibitor potential for psoriasis treatment through investigation of their therapeutic functions alongside their mechanism of action and clinical response, safety data, and novel treatment approaches. The review gathered detailed information about clinical research and pharmaceutical operations of PDE4 inhibitors, specifically for apremilast, roflumilast, and crisaborole. This review also analyzes experimental PDE4 inhibitors alongside the advantages that appear when combining these drugs with biologics or phototherapy, together with methotrexate. The administration of PDE4 inhibitors creates higher intracellular cAMP levels that decrease TNF-α and IL-17 production as pro-inflammatory cytokines. The research on Apremilast, as the most prominent oral PDE4 inhibitor, shows that it both improves PASI scores and maintains good safety results. These medications treat psoriasis symptoms specifically through creams and gels, thus reducing the risk of whole-body side effects. The combined administration of PDE4 inhibitors and biologics leads to better therapeutic effects, which may lower both drug resistance rates and side effects. PDE4 inhibitors function as a valuable alternative therapeutic approach to both standard immunosuppressants and biologic medications in psoriasis treatment. New drug dosage methods connected to personalized treatment plans have the potential to raise patient care effectiveness. Researchers need to study ways to improve PDE4 inhibitor formulations, along with developing new combination therapy approaches to enhance sustained psoriasis disease treatment.

摘要

被称为银屑病的慢性自身免疫性疾病给受影响的患者带来了严重的生活质量问题。该疾病通过遗传和环境触发因素演变,这些因素引发角质形成细胞持续增殖并伴有持续炎症。目前对银屑病治疗的研究重点是磷酸二酯酶-4(PDE4)抑制剂,因为它们可调节环磷酸腺苷(cAMP)信号传导,以减少炎性细胞因子的产生。本综述通过研究PDE4抑制剂的治疗功能、作用机制、临床反应、安全性数据和新的治疗方法,探讨其在银屑病治疗中的潜力。该综述收集了有关PDE4抑制剂临床研究和制药操作的详细信息,特别是针对阿普米司特、罗氟司特和克立硼罗。本综述还分析了实验性PDE4抑制剂,以及将这些药物与生物制剂或光疗以及甲氨蝶呤联合使用时出现的优势。PDE4抑制剂的给药可提高细胞内cAMP水平,从而降低作为促炎细胞因子的肿瘤坏死因子-α和白细胞介素-17的产生。对最著名的口服PDE4抑制剂阿普米司特的研究表明,它既能改善银屑病面积和严重程度指数(PASI)评分,又能保持良好的安全性结果。这些药物通过乳膏和凝胶专门治疗银屑病症状,从而降低全身副作用的风险。PDE4抑制剂与生物制剂联合给药可产生更好的治疗效果,这可能会降低耐药率和副作用。在银屑病治疗中,PDE4抑制剂是标准免疫抑制剂和生物药物的一种有价值的替代治疗方法。与个性化治疗方案相关的新药物给药方法有可能提高患者护理效果。研究人员需要研究改进PDE4抑制剂制剂的方法,以及开发新的联合治疗方法,以加强对银屑病的持续治疗。

相似文献

[1]
PDE4 inhibitors in psoriasis therapy: current insights and future directions.

Inflammopharmacology. 2025-5-15

[2]
Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

Cochrane Database Syst Rev. 2021-4-19

[3]
Phosphodiesterase 4 inhibitors for chronic obstructive pulmonary disease.

Cochrane Database Syst Rev. 2017-9-19

[4]
Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

Cochrane Database Syst Rev. 2020-1-9

[5]
Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

Cochrane Database Syst Rev. 2017-12-22

[6]
Chemical, Biochemical, and Structural Similarities and Differences of Dermatological cAMP Phosphodiesterase-IV Inhibitors.

J Invest Dermatol. 2025-6

[7]
[Phosphodiesterase 4 inhibitors in dermatology : Role in the treatment of skin diseases].

Dermatologie (Heidelb). 2024-10

[8]
Systemic pharmacological treatments for chronic plaque psoriasis: a network meta-analysis.

Cochrane Database Syst Rev. 2022-5-23

[9]
Phosphodiesterase-4 inhibitors reduce the expression of proinflammatory mediators by human epidermal keratinocytes independent of intracellular cAMP elevation.

J Dermatol Sci. 2020-12

[10]
Systematic review of comparative studies on emerging psoriasis treatments: comparing biologics with biologics, small molecule inhibitors with small molecule inhibitors, and biologics with small molecule inhibitors.

Inflammopharmacology. 2025-5-29

本文引用的文献

[1]
Cardiometabolic Effects of Apremilast in Patients With Psoriatic Arthritis: A Prospective Cohort Study.

J Rheumatol. 2025-4-1

[2]
Prevalence of fungal colonization among patients with psoriasis in difficult-to-treat areas: impact of apremilast on mycotic burden and clinical outcomes.

Front Immunol. 2024-12-10

[3]
Insilico discovery of novel Phosphodiesterase 4 (PDE4) inhibitors for the treatment of psoriasis: Insights from computer aided drug design approaches.

PLoS One. 2024

[4]
Roflumilast Cream, 0.15%, for Atopic Dermatitis in Adults and Children: INTEGUMENT-1 and INTEGUMENT-2 Randomized Clinical Trials.

JAMA Dermatol. 2024-11-1

[5]
Exploring Acne Treatments: From Pathophysiological Mechanisms to Emerging Therapies.

Int J Mol Sci. 2024-5-13

[6]
Efficacy and safety of apremilast in pediatric patients with moderate-to-severe plaque psoriasis: 16-week results from SPROUT, a randomized controlled trial.

J Am Acad Dermatol. 2024-6

[7]
Phosphodiesterase-4 Inhibition in the Management of Psoriasis.

Pharmaceutics. 2023-12-22

[8]
Resveratrol and Its Derivatives in Inflammatory Skin Disorders-Atopic Dermatitis and Psoriasis: A Review.

Antioxidants (Basel). 2023-11-2

[9]
Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS).

J Am Acad Dermatol. 2024-3

[10]
Next Generation PDE4 Inhibitors that Selectively Target PDE4B/D Subtypes: A Narrative Review.

Dermatol Ther (Heidelb). 2023-12

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