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银屑病和银屑病关节炎管理的新进展:聚焦阿普斯特

New developments in the management of psoriasis and psoriatic arthritis: a focus on apremilast.

作者信息

Palfreeman Andrew C, McNamee Kay E, McCann Fiona E

机构信息

The Kennedy Institute of Rheumatology, Nuffield Department of Orthopedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, London, UK.

出版信息

Drug Des Devel Ther. 2013;7:201-10. doi: 10.2147/DDDT.S32713. Epub 2013 Mar 27.

Abstract

Psoriasis is a chronic inflammatory skin disease, most commonly resulting in the occurrence of red and silver scaly plaques. About 30% of psoriasis sufferers develop psoriatic arthritis (PsA), a disorder that presents with additional joint inflammation and other clinical features. At present, the most effective treatment for moderate and severe psoriasis and PsA are biologics such as antitumor necrosis factor alpha therapy. Biologics are costly and typically require repeated injections; hence, the development of novel, orally available, small molecular inhibitors that are less expensive to produce is highly desirable. The phosphodiesterase 4 inhibitor apremilast is a small molecular inhibitor that acts by increasing cyclic adenosine monophosphate levels, ultimately suppressing tumor necrosis alpha production. Apremilast has been tested in a number of psoriasis and PsA pilot and Phase II trials to evaluate its efficacy and safety. More recently, three larger double-blinded, and randomized multicenter studies demonstrate that apremilast is efficacious in the treatment of psoriasis and PsA, with significantly higher numbers of apremilast-treated patients achieving endpoints of a 75% reduction compared to baseline in Psoriasis Area and Severity Index (PASI-75) or American College of Rheumatology-20 scores, relative to placebo. This encouraging data, along with a tolerable incidence of mild to moderate adverse events, has led to the initiation of several large Phase III trials that aim to further validate apremilast as a treatment for psoriasis and PsA. Here, we provide an overview of the current treatments for psoriasis and PsA, and summarize the findings from multiple Phase II clinical trials where the effects of apremilast in the treatment of psoriasis and PsA patients have been investigated.

摘要

银屑病是一种慢性炎症性皮肤病,最常见的表现是出现红色和银色鳞屑斑块。约30%的银屑病患者会发展为银屑病关节炎(PsA),这是一种伴有额外关节炎症和其他临床特征的病症。目前,治疗中度和重度银屑病及PsA最有效的方法是使用生物制剂,如抗肿瘤坏死因子α疗法。生物制剂成本高昂,通常需要反复注射;因此,开发新型、口服可用、生产成本较低的小分子抑制剂非常必要。磷酸二酯酶4抑制剂阿普斯特是一种小分子抑制剂,其作用机制是提高环磷酸腺苷水平,最终抑制肿瘤坏死因子α的产生。阿普斯特已在多项银屑病和PsA的试点及II期试验中进行了测试,以评估其疗效和安全性。最近,三项规模更大的双盲、随机多中心研究表明,阿普斯特在治疗银屑病和PsA方面有效,与安慰剂相比,接受阿普斯特治疗的患者达到银屑病面积和严重程度指数(PASI - 75)或美国风湿病学会20分评分相对于基线降低75%这一终点的人数显著更多。这些令人鼓舞的数据,以及轻度至中度不良事件的可耐受发生率,促使开展了多项大型III期试验,旨在进一步验证阿普斯特作为银屑病和PsA治疗药物的有效性。在此,我们概述了目前银屑病和PsA的治疗方法,并总结了多项II期临床试验的结果,这些试验研究了阿普斯特在治疗银屑病和PsA患者中的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/57d6/3615921/fae0bf2392a2/dddt-7-201Fig1.jpg

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