Arneson Laura C, Carroll Kristen J, Ruderman Eric M
Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Medicine, Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Immunotargets Ther. 2021 Aug 28;10:333-342. doi: 10.2147/ITT.S288550. eCollection 2021.
Bruton's tyrosine kinase (BTK) inhibitors are an emerging class of drugs that inhibit B cell receptor activation, FC-γ receptor signaling, and osteoclast proliferation. Following on approval for treatment of hematologic malignancies, BTK inhibitors are now under investigation to treat a number of different autoimmune diseases, including rheumatoid arthritis (RA). While the results of BTK inhibitors in RA animal models have been promising, the ensuing human clinical trial outcomes have been rather equivocal. This review will outline the mechanisms of BTK inhibition and its potential impact on immune mediated disease, the types of BTK inhibitors being studied for RA, the findings from both preclinical and clinical trials of BTK inhibitors in RA, and directions for future research.
布鲁顿酪氨酸激酶(BTK)抑制剂是一类新兴药物,可抑制B细胞受体激活、Fc-γ受体信号传导和破骨细胞增殖。在获批用于治疗血液系统恶性肿瘤后,BTK抑制剂目前正在接受研究,以治疗多种不同的自身免疫性疾病,包括类风湿性关节炎(RA)。虽然BTK抑制剂在RA动物模型中的结果很有前景,但随后的人体临床试验结果却相当模糊。本综述将概述BTK抑制的机制及其对免疫介导疾病的潜在影响、正在研究用于RA的BTK抑制剂类型、BTK抑制剂在RA的临床前和临床试验结果,以及未来的研究方向。