Baylor Research Institute, Baylor University Medical Center, 3900 Junius Street Suite 125, Dallas, TX 75246 USA.
Dermatol Ther (Heidelb). 2012 Dec;2(1):16. doi: 10.1007/s13555-012-0016-4. Epub 2012 Oct 25.
Psoriasis is an immune-mediated disease that affects 1%-2% of the European and North American population. While topical agents such as corticosteroids and vitamin D derivatives are prescribed for mild disease, they are generally unable to adequately control patients with more severe disease. Over the past decade, research into the immunopathogenesis of psoriasis, including investigations into the role of tumor necrosis factor-alpha and more recently interleukins (IL) 12/23, has led to the advent of targeted biologic therapies based on the central role of a new subset of T cells, Th17. Because of their increased specificity, biologic agents have revolutionized short- to medium-term treatment outcomes and safety profiles for moderate to severe disease over previously gold standard systemic agents. The immunopathogenesis of the disease is still a focus for researchers and novel targets for future agents are being discovered and investigated in clinical trials. In particular, specifically targeting the IL-23/Th17 pathway has given rise to IL-23p19 and IL-17 antagonists, both of which have shown significant promise in clinical trials. IL-22 is involved in keratinocyte proliferation and is being studied as a treatment target for psoriasis. New small molecule oral agents, including Janus kinase and phosphodiesterase inhibitors are currently in phase 2 and 3 clinical trials.
银屑病是一种免疫介导的疾病,影响欧洲和北美的 1%-2%的人口。虽然皮质类固醇和维生素 D 衍生物等局部药物用于治疗轻度疾病,但它们通常无法充分控制病情更严重的患者。在过去的十年中,对银屑病的免疫发病机制的研究,包括对肿瘤坏死因子-α的作用的研究以及最近对白细胞介素(IL)12/23 的研究,导致了基于新的 T 细胞亚群(Th17)的靶向生物疗法的出现。由于它们的特异性增加,生物制剂彻底改变了中重度疾病的短期至中期治疗结果和安全性,优于以前的金标准全身药物。该疾病的免疫发病机制仍然是研究人员关注的焦点,并且正在临床试验中发现和研究用于未来药物的新靶点。特别是,针对 IL-23/Th17 途径的特异性靶向治疗已经产生了 IL-23p19 和 IL-17 拮抗剂,两者在临床试验中均显示出巨大的潜力。IL-22 参与角质形成细胞增殖,正在作为银屑病的治疗靶点进行研究。新型小分子口服药物,包括 Janus 激酶和磷酸二酯酶抑制剂,目前正在进行 2 期和 3 期临床试验。