目的: 探讨艾拉莫德联合托法替布在难治性中重度类风湿关节炎(rheumatoid arthritis, RA)患者中的疗效和安全性。方法: 选择2021年9月至2022年6月规律就诊于山西省汾阳医院风湿免疫科的难治性中重度活动性RA患者30例进行前瞻性临床研究，其中，23例患者采用≥2种传统合成改善病情抗风湿药(disease modifying anti-rheumatic drugs，DMARDs)(至少包括甲氨蝶呤或来氟米特)治疗6个月以上，7例患者采用传统合成DMARDs联合肿瘤坏死因子拮抗剂治疗。将DMARDs调整为艾拉莫德联合托法替布，共治疗12周，收集患者治疗前，治疗4周、8周及12周时的临床资料：肿胀关节数(swollen joints count，SJC)、疼痛关节数(tender joints count，TJC)、晨僵时间、临床疾病活动指数(clinical disease activity index，CDAI)、健康状况评估问卷(health status assessment questionnaire，HAQ)、28个关节计数的疾病活动评分(28-joint disease activity score，DAS28)。记录患者的红细胞沉降率(erythrocyte sedimentation rate, ESR)、C反应蛋白(C-reactive protein, CRP)、血小板(platelet, PLT)、类风湿因子(rheumatoid factor, RF)、球蛋白、抗环瓜氨酸肽(cyclic citrullinated peptide, CCP)抗体等实验室检查结果，记录患者的用药情况，比较患者疾病活动指标的变化情况，记录药物不良反应。结果: 比较治疗前后的ESR、CRP、RF、PLT、SJC、TJC、基于ESR的DAS28(DAS28-ESR)、晨僵时间、HAQ、CDAI、抗CCP抗体，差异均有统计学意义(P < 0.05)，而治疗前后的球蛋白比较差异无统计学意义(P>0.05)。艾拉莫德联合托法替布治疗期间，所有患者均未发生白细胞减少、肝酶明显升高、过敏、血栓栓塞等严重不良反应。结论: 艾拉莫德联合托法替布治疗难治性中重度RA，可通过降低炎性指标改善患者的近期临床症状，且安全性良好。

Objective: To investigate the efficacy and safety of iguratimod combined with tofacitinib in patients with difficult-to-treat moderate-to-severe rheumatoid arthritis (RA). Methods: In this prospective clinical study, 30 patients with difficult-to-treat moderate-to-severe RA who attended the Department of Rheumatology and Immunology of Shanxi Province Fenyang Hospital from September 2021 to June 2022 were selected. Twenty-three patients enrollment had been treated with 2 or more conventional synthetic disease modifying anti-rheumatic drugs (DMARDs) for more than 6 months. At least, methotrexate or leflunomide was included. Seven patients were treated with conventional synthetic DMARDs combined with tumor necrosis factor antagonists. Because all the patients had not reached the target of treatment, the combination treatment regimen of DMARDs was changed to iguratimod and tofacitinib. The observation period was 12 weeks. Clinical data were collected before and after treatment. At the end of 4 weeks, 8 weeks and 12 weeks, the clinical data were collected such as swollen joints count (SJC), tender joints count (TJC), time of morning stiffness, clinical disease activity index (CDAI), health status assessment questionnaire (HAQ), and 28-joint disease activity score (DAS28) were included. We collected laboratory indicators, recorded the patient's medication, and observed some changes to see if any adverse drug reactions occurred during the treatment. Results: There were significant differences in erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), platelet (PLT), SJC, TJC, DAS28 based on ESR(DAS28-ESR), time of morning stiffness, HAQ, CDAI, and anti-cyclic citrullinated peptide antibody before and after treatment. The differences had statistical significance (P < 0.05). There was no statistical differences in globulin before and after treatment (P>0.05). During the treatment of iguratimod combined with tofacitinib, there was no serious adverse reactions such as leukopenia, significant elevation of liver enzymes, allergy or thromboemblolic events that occurred in all the patients. Conclusion: Iguratimod combined with tofacitinib in the treatment of difficult-to-treat moderate-to-severe RA may have efficacy. The machanism was improving the patients' recent clinical symptoms by reducing inflammatory indexes. This combination treatment regimen with iguratimod and tofacitinib has a good safety profile.