Puig Lluís
a Department of Dermatology, Hospital de la Santa Creu i Sant Pau , Universitat Autònoma de Barcelona , Barcelona , Catalonia , Spain.
Expert Rev Clin Immunol. 2017 Jun;13(6):525-534. doi: 10.1080/1744666X.2017.1292137. Epub 2017 Feb 20.
The IL-23/IL-17 axis is currently considered to be crucial in the pathogenesis of psoriasis. Human IL-23 is primarily produced by antigen-presenting cells and induces and maintains differentiation of Th17 cells and Th22 cells, a primary cellular source of proinflammatory cytokines such as IL-17 and IL-22, which mediate the epidermal hyperplasia, keratinocyte immune activation and tissue inflammation inherent in psoriasis. Agents that target the p40 subunit common to both IL-12 and IL-23 have shown robust clinical activity, but selectivity for IL-23p19 could offer advantages in efficacy and safety with respect to anti-p40 blockade. Areas covered: Relevant references regarding the role of the IL-23/IL-17 pathway in the pathogenesis of psoriasis/psoriatic arthritis and clinical trials with IL-23p40 and IL-23p19 blocking agents were obtained through a literature search in MEDLINE/Pubmed for articles published until November 2016. Moreover, ongoing registered clinical trials (RCTs) of moderate-to-severe psoriasis and psoriatic arthritis were searched through clinicaltrials.gov website, and a manual search was made for pertinent communications at the 2016 American Academy of Dermatology and European Academy of Dermatology and Venereology meetings. Expert commentary: There are potential advantages in selective blockade of the IL23-specific p19 subunit with respect to distal blockade of IL-17A or its receptor. Acting upstream in the IL-23/IL-17 cytokine pathway is likely to reduce the expression of multiple pro-inflammatory cytokines acting on keratinocytes -including IL-17F, IL-21 and IL-22-, in addition to IL-17A. On the other hand, safety data thus far suggest that these drugs might be devoid of some adverse effects of IL-17A blockade that seem to be class related, such as mucocutaneous Candida infections or triggering or worsening of inflammatory bowel disease. Specific IL-23p19 blockade with high-affinity monoclonal antibodies seems to be able to induce long-term remissions of the activity in psoriasis and might eventually represent a paradigm change in the treatment of psoriasis. The results of phase III and comparative head-to-head trials with these agents are eagerly awaited.
白细胞介素-23/白细胞介素-17轴目前被认为在银屑病的发病机制中起关键作用。人白细胞介素-23主要由抗原呈递细胞产生，可诱导并维持Th17细胞和Th22细胞的分化，而Th17细胞和Th22细胞是白细胞介素-17和白细胞介素-22等促炎细胞因子的主要细胞来源，这些细胞因子介导了银屑病固有的表皮增生、角质形成细胞免疫激活和组织炎症。靶向白细胞介素-12和白细胞介素-23共有的p40亚基的药物已显示出强大的临床活性，但对白细胞介素-23 p19的选择性在疗效和安全性方面可能优于抗p40阻断剂。涵盖领域：通过在MEDLINE/Pubmed中检索截至2016年11月发表的文章，获取了关于白细胞介素-23/白细胞介素-17通路在银屑病/银屑病关节炎发病机制中的作用以及白细胞介素-23 p40和白细胞介素-23 p19阻断剂的临床试验的相关参考文献。此外，通过clinicaltrials.gov网站检索了正在进行的中重度银屑病和银屑病关节炎的注册临床试验（RCT），并在2016年美国皮肤病学会和欧洲皮肤病与性病学会会议上进行了相关通讯的手工检索。专家评论：相对于白细胞介素-17A或其受体的远端阻断，选择性阻断白细胞介素-23特异性p19亚基具有潜在优势。在白细胞介素-23/白细胞介素-17细胞因子通路中作用于上游可能会降低作用于角质形成细胞的多种促炎细胞因子的表达，包括白细胞介素-17F、白细胞介素-21和白细胞介素-22，以及白细胞介素-17A。另一方面，目前的安全性数据表明，这些药物可能没有白细胞介素-17A阻断剂似乎与之相关的一些不良反应，如皮肤黏膜念珠菌感染或炎症性肠病的触发或恶化。用高亲和力单克隆抗体特异性阻断白细胞介素-23 p19似乎能够诱导银屑病活性的长期缓解，并最终可能代表银屑病治疗的范式转变。人们急切期待这些药物的III期试验和对比性的头对头试验结果。
