Rheumatoid arthritis (RA) is a systemic autoimmune disease, which is characterized by a chronic fluctuating course and immune dysfunction, resulting in affecting the health and life quality of RA patients. Methotrexate (MTX), as the standard gold treatment of RA, has received more and more clinical applications and basic pharmacological research. In several observational studies, MTXR, and treatment responses in RA patients show that the ratio of MTXR and non- response is about 30%–50%, namely MTX resistance (MTXR). Extensive efforts have been made into the investigation of the mechanism and effective biomarkers in MTXR of RA. In this paper, we discuss the recent findings regarding the critical signaling pathways of MTXR in RA. Provide research targets and directions for a drug therapy that develop preventive strategies and effective treatments of MTXR.

类风湿关节炎（RA）是一种全身性自身免疫性疾病，其特征是慢性波动过程和免疫功能障碍，从而影响RA患者的健康和生活质量。甲氨蝶呤（MTX）作为RA的标准黄金治疗方法，已收到越来越多的临床应用和基础药理研究。在一些观察性研究中，RA患者的MTXR和治疗反应表明，MTXR与无反应的比率约为30％–50％，即MTX耐药性（MTXR）。已经广泛研究RA的MTXR的机制和有效的生物标志物。在本文中，我们讨论了有关RA中MTXR关键信号通路的最新发现。