Department of Dermatology, Centro Hospitalar do Porto, Porto, Portugal.
Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
BioDrugs. 2018 Apr;32(2):119-128. doi: 10.1007/s40259-018-0265-6.
Psoriasis is a common, chronic, immune-mediated, inflammatory skin disease with systemic involvement and significant impact on patients' quality of life. Several biologic treatments have been developed in recent decades, such as tumor necrosis factor (TNF)-α inhibitors, a non-selective interleukin (IL)-23 inhibitor (ustekinumab, which also inhibits IL-12), and-most recently-IL-17 inhibitors. Guselkumab is a novel biological therapy that selectively targets IL-23 and is the first-in-class selective IL-23 inhibitor approved to treat moderate-to-severe plaque psoriasis. These inhibitors are expected to have some advantages over the highly effective IL-17 inhibitors, as they do not worsen inflammatory bowel disease and are not involved in the development of candida infections. Additionally, selective inhibition of IL-23 may have additional benefits over ustekinumab as the IL-12-dependent cascades remain functional. These benefits include a decrease in IL-17A-producing T cells in the skin and the promotion of an anti-inflammatory effect through production of interferon-γ and IL-10. In terms of efficacy, guselkumab showed promising results in the treatment of psoriasis and psoriatic arthritis, although it did not show significant clinical improvement in rheumatoid arthritis. Studies in other inflammatory diseases and Crohn's disease are expected to begin soon. Overall, guselkumab was well tolerated; the most common adverse event was nasopharyngitis. Head-to-head studies comparing IL-23 inhibitors with agents in different classes, namely IL-17 inhibitors, will be crucial to establish the true role of these agents in psoriasis treatment.
银屑病是一种常见的、慢性的、免疫介导的炎症性皮肤病,可累及全身,对患者的生活质量有重大影响。近几十年来,已经开发出几种生物疗法,如肿瘤坏死因子(TNF)-α抑制剂、非选择性白细胞介素(IL)-23 抑制剂(乌司奴单抗,也抑制 IL-12),以及最近的 IL-17 抑制剂。古塞库单抗是一种新型的生物疗法,可选择性靶向 IL-23,是首个获批用于治疗中重度斑块型银屑病的选择性 IL-23 抑制剂。与高效的 IL-17 抑制剂相比,这些抑制剂有望具有一些优势,因为它们不会加重炎症性肠病,也不会参与念珠菌感染的发生。此外,选择性抑制 IL-23 可能比乌司奴单抗具有更多的益处,因为 IL-12 依赖性级联反应仍然具有功能。这些益处包括皮肤中产生 IL-17A 的 T 细胞减少,以及通过产生干扰素-γ 和 IL-10 促进抗炎作用。在疗效方面,古塞库单抗在治疗银屑病和银屑病关节炎方面显示出了有前景的结果,尽管在类风湿关节炎方面并未显示出显著的临床改善。预计很快就会开始在其他炎症性疾病和克罗恩病中进行研究。总体而言,古塞库单抗具有良好的耐受性;最常见的不良反应是鼻咽炎。比较 IL-23 抑制剂与不同类别药物(即 IL-17 抑制剂)的头对头研究对于确定这些药物在银屑病治疗中的真正作用至关重要。