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治疗银屑病的新兴口服疗法:在研药物综述

Emerging Oral Therapies for the Treatment of Psoriasis: A Review of Pipeline Agents.

作者信息

Drakos Anastasia, Torres Tiago, Vender Ronald

机构信息

Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.

Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal.

出版信息

Pharmaceutics. 2024 Jan 15;16(1):111. doi: 10.3390/pharmaceutics16010111.

Abstract

The introduction of biologic agents for the treatment of psoriasis has revolutionized the current treatment landscape, targeting cytokines in the interleukin (IL)-23/IL-17 pathway and demonstrating strong efficacy and safety profiles in clinical trials. These agents however are costly, are associated with a risk of immunogenicity, and require administration by intravenous or subcutaneous injection, limiting their use among patients. Oral therapies, specifically small molecule and microbiome therapeutics, have the potential to be more convenient and cost-effective agents for patients and have been a focus of development in recent years, with few targeted oral medications available for the disease. In this manuscript, we review pipeline oral therapies for psoriasis identified through a search of ClinicalTrials.gov (30 June 2022-1 October 2023). Available preclinical and clinical trial data on each therapeutic agent are discussed. Small molecules under development include tumor necrosis factor inhibitors, IL-23 inhibitors, IL-17 inhibitors, phosphodiesterase-4 inhibitors, Janus kinase inhibitors, A3 adenosine receptor agonists, and sphingosine-1-phosphate receptor 1 agonists, several of which are entering phase III trials. Oral microbials have also demonstrated success in early phase studies. As new oral therapies emerge for the treatment of psoriasis, real-world data and comparative trials are needed to better inform their use among patients.

摘要

用于治疗银屑病的生物制剂的引入彻底改变了当前的治疗格局,其作用于白细胞介素(IL)-23/IL-17通路中的细胞因子,并在临床试验中显示出强大的疗效和安全性。然而,这些药物成本高昂,存在免疫原性风险,且需要通过静脉或皮下注射给药,限制了它们在患者中的使用。口服疗法,特别是小分子和微生物组疗法,有可能为患者提供更方便且具成本效益的药物,并且近年来一直是研发的重点,目前针对该疾病的靶向口服药物较少。在本手稿中,我们回顾了通过检索ClinicalTrials.gov(2022年6月30日至2023年10月1日)确定的银屑病口服治疗药物研发管线。讨论了每种治疗药物的可用临床前和临床试验数据。正在研发的小分子药物包括肿瘤坏死因子抑制剂、IL-23抑制剂、IL-17抑制剂、磷酸二酯酶-4抑制剂、Janus激酶抑制剂、A3腺苷受体激动剂和鞘氨醇-1-磷酸受体1激动剂,其中几种已进入III期试验。口服微生物制剂在早期研究中也取得了成功。随着用于治疗银屑病的新型口服疗法的出现,需要真实世界数据和对比试验来更好地指导它们在患者中的使用。

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