Insights into rheumatoid arthritis (RA) have slowly evolved over the last century, but with breathtaking speed over the last 2 decades. While only aspirin and parenteral gold were available in early 20th century, the efficacy of sulfasalazine, glucocorticoids and methotrexate was established around its middle. Identification of pathogenetic pathways was slow, and until today the role of T-cells is enigmatic, while it is clear that genetics via the shared epitope and other genes as well as environmental factors including the metagenome play major roles. More clarity evolved on importance of proinflammatory cytokines, especially TNF and IL-6. The activation of osteoclasts, the culprits of bony joint damage, is amplified by the proinflammatory cytokines. The realization of TNF's central role led to the successful introduction of TNF-inhibitors and subsequently also inhibitors of other cytokines and cells as well as signal transduction. In parallel, the evolution of outcomes research has contributed importantly to RA management. At the turn to the 21st century, improvement criteria and continuous indices were created, allowing reliable therapeutic response determination, including definition of endpoints like remission. Also our understanding of the role of disease activity relative to disease pathology has increased, ultimately fostering the treat-to-target concept and recommendations and, thus, optimal outcomes for RA patients as never been seen before. Similar developments are now ultimately being introduced in the field of psoriatic arthritis. Here many of these aspects are reviewed from a very personal perspective of the author in the hopes of further helping parients with chronic forms of arthritis.

中文翻译：

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深入了解类风湿性关节炎的治疗：医学范式。

对类风湿性关节炎 (RA) 的了解在上个世纪缓慢发展，但在过去 20 年中以惊人的速度发展。虽然在 20 世纪初期只有阿司匹林和注射用金可用，但柳氮磺吡啶、糖皮质激素和甲氨蝶呤的疗效却在其中期确立。致病途径的鉴定很慢，直到今天，T 细胞的作用仍然是个谜，而很明显，通过共享表位和其他基因以及包括宏基因组在内的环境因素的遗传学起主要作用。促炎细胞因子，尤其是 TNF 和 IL-6 的重要性得到了更清晰的发展。破骨细胞（骨关节损伤的罪魁祸首）的激活被促炎细胞因子放大。TNF'的实现 其核心作用导致成功引入 TNF 抑制剂，随后还有其他细胞因子和细胞的抑制剂以及信号转导。与此同时，结果研究的发展对 RA 管理做出了重要贡献。在进入 21 世纪之际，创建了改进标准和连续指数，从而可以确定可靠的治疗反应，包括定义缓解等终点。此外，我们对疾病活动相对于疾病病理的作用的理解有所增加，最终形成了治疗目标的概念和建议，从而为 RA 患者提供了前所未有的最佳结果。类似的发展现在最终被引入银屑病关节炎领域。