Taylor Peter C, Feldmann Marc
Kennedy Institute of Rheumatology Division, Imperial College, London, UK.
Nat Rev Rheumatol. 2009 Oct;5(10):578-82. doi: 10.1038/nrrheum.2009.181.
Cytokines such as tumor necrosis factor (TNF) are expressed at high levels in rheumatoid joint tissue, where they contribute significantly to inflammation and articular destruction. TNF was the first cytokine to be fully validated as a therapeutic target for rheumatoid arthritis (RA). In nearly a decade since anti-TNF agents-such as infliximab, etanercept and adalimumab-were launched as the first biologic therapies to be licensed for RA, much has been learnt about how and when in the disease course this class of drug can be used to achieve optimal therapeutic benefit. Other cytokine targets, such as interleukin (IL)-6 or IL-1, have also been validated and several are in the process of being tested. However, TNF is likely to remain the preferred target of first-line biologic therapy for the foreseeable future as, in populations with active RA despite ongoing, nonbiologic, DMARD therapy, biologic inhibition of either IL-6 or IL-1 demonstrates no obviously superior outcomes to TNF blockade. Furthermore, new approaches to blockade of signaling mediated by bioactive TNF might have the potential to generate higher-magnitude clinical responses than are currently elicited.
细胞因子如肿瘤坏死因子（TNF）在类风湿关节组织中高表达，在那里它们对炎症和关节破坏有显著作用。TNF是第一个被充分验证为类风湿关节炎（RA）治疗靶点的细胞因子。自从英夫利昔单抗、依那西普和阿达木单抗等抗TNF药物作为首批获批用于RA的生物疗法上市近十年来，人们对这类药物在疾病进程中如何以及何时使用才能获得最佳治疗效果有了很多了解。其他细胞因子靶点，如白细胞介素（IL）-6或IL-1，也已得到验证，有几种正在测试中。然而，在可预见的未来，TNF可能仍将是一线生物治疗的首选靶点，因为在尽管正在进行非生物改善病情抗风湿药（DMARD）治疗但仍患有活动性RA的人群中，对IL-6或IL-1进行生物抑制并未显示出比TNF阻断有明显更好的疗效。此外，阻断生物活性TNF介导的信号传导的新方法可能有潜力产生比目前更高程度的临床反应。
