Koenders Marije I, van den Berg Wim B
Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
Drug Des Devel Ther. 2016 Jun 24;10:2069-80. doi: 10.2147/DDDT.S105263. eCollection 2016.
Rheumatic disease is not a single disorder, but a group of more than 100 diseases that affect joints, connective tissues, and/or internal organs. Although rheumatic diseases like rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis (AS) differ in their pathogenesis and clinical presentation, the treatment of these inflammatory disorders overlaps. Non-steroid anti-inflammatory drugs are used to reduce pain and inflammation. Additional disease-modifying anti-rheumatic drugs are prescribed to slowdown disease progression, and is in RA more frequently and effectively applied than in AS. Biologicals are a relatively new class of treatments that specifically target cytokines or cells of the immune system, like tumor necrosis factor alpha inhibitors or B-cell blockers. A new kid on the block is the interleukin-17 (IL-17) inhibitor secukinumab, which has been recently approved by the US Food and Drug Administration for moderate-to-severe plaque psoriasis, psoriatic arthritis, and AS. IL-17 is a proinflammatory cytokine that has an important role in host defense, but its proinflammatory and destructive effects have also been linked to pathogenic processes in autoimmune diseases like RA and psoriasis. Animal models have greatly contributed to further insights in the potential of IL-17 blockade in autoimmune and autoinflammatory diseases, and have resulted in the development of various potential drugs targeting the IL-17 pathway. Secukinumab (AIN457) is a fully human monoclonal antibody that selectively binds to IL-17A and recently entered the market under the brand name Cosentyx(®). By binding to IL-17A, secukinumab prevents it from binding to its receptor and inhibits its ability to trigger inflammatory responses that play a role in the development of various autoimmune diseases. With secukinumab being the first in class to receive Food and Drug Administration approval, this article will further focus on this new biologic agent and review the milestones in its development and marketing.
风湿性疾病并非单一病症,而是一组超过100种影响关节、结缔组织和/或内脏器官的疾病。尽管类风湿性关节炎(RA)、银屑病关节炎和强直性脊柱炎(AS)等风湿性疾病在发病机制和临床表现上有所不同,但这些炎症性疾病的治疗存在重叠。非甾体抗炎药用于减轻疼痛和炎症。另外还会开具改善病情抗风湿药以减缓疾病进展,且在RA中比在AS中更频繁、有效地应用。生物制剂是一类相对较新的治疗方法,专门针对免疫系统的细胞因子或细胞,如肿瘤坏死因子α抑制剂或B细胞阻滞剂。新出现的是白细胞介素-17(IL-17)抑制剂司库奇尤单抗,它最近已获美国食品药品监督管理局批准用于中度至重度斑块状银屑病、银屑病关节炎和AS。IL-17是一种促炎细胞因子,在宿主防御中起重要作用,但其促炎和破坏作用也与RA和银屑病等自身免疫性疾病的致病过程有关。动物模型极大地有助于进一步深入了解IL-17阻断在自身免疫性和自身炎症性疾病中的潜力,并促成了各种靶向IL-17途径的潜在药物的研发。司库奇尤单抗(AIN457)是一种完全人源化单克隆抗体,可选择性结合IL-17A,最近以可善挺(Cosentyx®)的品牌进入市场。通过结合IL-17A,司库奇尤单抗可防止其与受体结合,并抑制其引发在各种自身免疫性疾病发展中起作用的炎症反应的能力。鉴于司库奇尤单抗是同类产品中首个获得食品药品监督管理局批准的药物,本文将进一步聚焦于这种新型生物制剂,并回顾其研发和上市历程中的重要节点。