Department of Medicine, Ruttonjee Hospital, Hong Kong, China.
Department of Medicine, Tuen Mun Hospital, Hong Kong, China.
Expert Opin Biol Ther. 2024 Jul;24(7):599-613. doi: 10.1080/14712598.2024.2358165. Epub 2024 May 22.
Rheumatoid arthritis (RA) is a chronic inflammatory rheumatic disease that affects both the articular and extra-articular structures, leading to significant joint damage, disability and excess mortality. The treatment algorithm of RA has changed tremendously in the past 1-2 decades because of the emergence of novel biological therapies that target different mechanisms of action in addition to TNFα.
This article summarizes the evidence and safety of the non-TNF biological DMARDs in the treatment of RA, including those that target B cells, T-cell co-stimulation, interleukin (IL)-6 and granulocyte-monocyte colony-stimulating factor (GM-CSF). The targeted synthetic DMARDs such as the Janus kinase inhibitors are not included. The availability of the less costly biosimilars has enabled more patients to receive biological therapy earlier in the course of the disease. The evidence for the non-TNF biosimilar compounds in RA is also reviewed.
There are unmet needs of developing novel therapeutic agents to enhance the response rate and provide more options for difficult-to-treat RA. These include the newer generation biologic and targeted synthetic DMARDs. A personalized treatment strategy in RA requires evaluation of the cellular, cytokine, genomic and transcriptomic profile that would predict treatment response to biologic or targeted DMARDs of different mechanisms of action.
类风湿关节炎(RA)是一种慢性炎症性风湿性疾病,影响关节和关节外结构,导致严重的关节损伤、残疾和过高的死亡率。由于新型生物疗法的出现,除了 TNFα 以外,还针对不同的作用机制,RA 的治疗方案在过去 1-2 十年发生了巨大变化。
本文总结了除 TNF 以外的生物 DMARD 在 RA 治疗中的证据和安全性,包括针对 B 细胞、T 细胞共刺激、白细胞介素(IL)-6 和粒细胞-巨噬细胞集落刺激因子(GM-CSF)的生物 DMARD。不包括靶向合成 DMARD,如 Janus 激酶抑制剂。更便宜的生物类似物的出现使更多的患者能够在疾病早期接受生物治疗。RA 中针对非 TNF 生物类似物的证据也进行了综述。
开发新型治疗药物以提高应答率并为治疗困难的 RA 提供更多选择存在未满足的需求。这些包括新一代生物制剂和靶向合成 DMARD。RA 的个性化治疗策略需要评估细胞、细胞因子、基因组和转录组特征,以预测对不同作用机制的生物或靶向 DMARD 的治疗反应。