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平衡疗效与肝毒性:银屑病治疗中口服药物的综合综述

Balancing efficacy and hepatotoxicity: a comprehensive review of oral medications in psoriasis management.

作者信息

Elsisi Alaa E, Abu-Risha Sally El-Sayed, Alkabbani Mahmoud Abdelrahman, Ramadan Laila A, Sokar Samia Salem

机构信息

Department of Pharmacology & Toxicology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Department of Pharmacology & Toxicology, Faculty of Pharmacy, Egyptian Russian University, Cairo, 11829, Egypt.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2025 Jun 25. doi: 10.1007/s00210-025-04334-1.

Abstract

Psoriasis is a chronic, immune-mediated inflammatory disorder that significantly impacts patients' quality of life. Oral systemic therapies, including methotrexate, cyclosporine, acitretin, and apremilast, remain integral to psoriasis management, particularly for patients with moderate-to-severe disease who cannot afford biologic therapy. While these treatments are effective, their long-term use is often limited by adverse effects, particularly hepatotoxicity. Methotrexate and acitretin are associated with liver toxicity, requiring regular monitoring, whereas cyclosporine presents a lower but notable risk. Apremilast, a phosphodiesterase 4 inhibitor, offers a safer hepatic profile but has lower efficacy than traditional systemic agents. Emerging therapies, such as TYK2 inhibitors, RORγt inhibitors, and novel PDE4 inhibitors, aim to improve treatment efficacy while minimizing adverse effects. Advances in understanding hepatotoxicity mechanisms have led to identifying predictive biomarkers and hepatoprotective strategies, including antioxidants and non-invasive imaging techniques. Personalized medicine approaches, including pharmacogenomics, are revolutionizing treatment selection by optimizing efficacy while minimizing toxicity risks. This comprehensive review examines oral psoriasis treatments' efficacy and hepatotoxicity profiles, discusses novel therapeutic developments, and explores strategies for mitigating liver-related adverse effects. A balanced approach that integrates clinical monitoring, lifestyle modifications, and emerging precision medicine techniques is essential for optimizing long-term treatment outcomes. Future research should focus on refining predictive models for drug-induced liver injury and developing targeted therapies with improved efficacy and safety profiles.

摘要

银屑病是一种慢性、免疫介导的炎症性疾病,严重影响患者的生活质量。口服全身治疗,包括甲氨蝶呤、环孢素、阿维A和阿普米司特,仍然是银屑病治疗的重要组成部分,特别是对于那些负担不起生物治疗的中度至重度疾病患者。虽然这些治疗方法有效,但它们的长期使用往往受到不良反应的限制,尤其是肝毒性。甲氨蝶呤和阿维A与肝毒性有关,需要定期监测,而环孢素的风险较低但值得注意。阿普米司特是一种磷酸二酯酶4抑制剂,具有更安全的肝脏特性,但疗效低于传统全身药物。新兴疗法,如酪氨酸激酶2(TYK2)抑制剂、维甲酸相关孤儿受体γt(RORγt)抑制剂和新型磷酸二酯酶4(PDE4)抑制剂,旨在提高治疗效果,同时将不良反应降至最低。对肝毒性机制认识的进展导致了预测性生物标志物的识别和肝脏保护策略的制定,包括抗氧化剂和非侵入性成像技术。包括药物基因组学在内的个性化医疗方法正在彻底改变治疗选择,通过优化疗效同时将毒性风险降至最低。这篇综述全面研究了口服银屑病治疗方法疗效和肝毒性特征,讨论了新的治疗进展,并探讨了减轻肝脏相关不良反应的策略。综合临床监测、生活方式调整和新兴精准医疗技术的平衡方法对于优化长期治疗结果至关重要。未来的研究应专注于完善药物性肝损伤的预测模型,并开发具有更高疗效和安全性的靶向治疗方法。

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