目的 探究高剂量托法替布联合甲氨蝶呤（MTX）对难治性类风湿性关节炎（RRA）患者临床疗效、血清抗环瓜氨酸肽抗体（anti-CCP）及辅助性T细胞17（Th17）相关细胞因子的影响。 方法 随机数字表法将青岛市中医医院2023年1月至2025年6月诊治的160例RRA患者分为高剂量组54例、低剂量组53例与对照组53例，分别接受高剂量托法替布（每次5 mg，每天2次）+ MTX（每次10 mg，每周1次）、低剂量托法替布（每次5 mg，每天1次）+ MTX（每次10 mg，每周1次）、益赛普（每次25 mg，每周2次）+ MTX（每次10 mg，每周1次）治疗，均持续治疗24周。以美国风湿病学会（ACR）标准评估的临床疗效为主要疗效终点，以治疗前后临床症状、生化指标［血沉（ESR）、C反应蛋白（CRP）］、血清anti-CCP、Th17相关细胞因子、Janus激酶（JAK）3、信号转导和转录激活因子（STAT）3变化及安全性为次要终点。 结果 高剂量组ACR50（76.92% vs. 50.00%）及ACR70（48.08% vs. 24.00%）比例均显著高于对照组（P < 0.05）。对比治疗前，3组患者治疗后临床症状相关指标、血清ESR、CRP、anti-CCP、类风湿因子（RF）、Th17及其相关细胞因子、JAK3、STAT3水平均显著下降（P < 0.05），高剂量组治疗后上述指标均显著低于低剂量组、对照组（P < 0.05），低剂量组治疗后疼痛视觉模拟评分、基于ESR的28个关节计数的疾病活动评分、血清Th17及其相关细胞因子、JAK3、STAT3水平均显著低于对照组（P < 0.05）。3组不良反应发生率（25.00% vs. 15.38% vs. 20.00%）对比无统计学意义（P > 0.05）。 结论 高剂量托法替布相比低剂量托法替布或益赛普联合MTX治疗RRA的疗效更好，能明显缓解患者临床症状，降低血清anti-CCP、Th17相关细胞因子、JAK3/STAT3水平，且未明显增多不良反应。

Objective To explore the clinical efficacy of high-dose tofacitinib in combination with methotrexate （MTX） for patients with refractory rheumatoid arthritis （RRA）， and its influence on serum anti-cyclic citrullinated peptide antibody （anti-CCP） and helper T cell 17 （Th17） -related cytokines. Methods The random number table method was used to divide 160 RRA patients treated in Qingdao Traditional Chinese Medicine Hospital from January 2023 to June 2025 into the high-dose group （54 cases）， the low-dose group （53 cases）， and the control group （53 cases）. These patients were respectively treated with high-dose tofacitinib （5 mg/time， twice a day） + MTX （10 mg/time， once a week）， low-dose tofacitinib （5 mg/time， once a day） + MTX （10 mg/time， once a week）， and Etanercept （25 mg/time， twice a week） + MTX （10 mg/time， once a week）， all for a 24-week treatment period. The clinical efficacy was evaluated according to the standards of the American College of Rheumatology （ACR） as the primary endpoint of the study. The secondary endpoints included changes in clinical symptoms， biochemical indicators ［erythrocyte sedimentation rate （ESR）， C-reactive protein （CRP）］， serum anti-CCP， Th17-related cytokines， Janus kinase （JAK） 3， signal transducer and activator of transcription （STAT） 3， and safety before and after treatment. Results The proportions of patients achieving ACR50 （76.92% vs. 50.00%） and ACR70 （48.08% vs. 24.00%） in the high-dose group were markedly higher than those in the control group （P < 0.05）. When compared with the pre-treatment state， the clinical symptom-related indicators， serum ESR， CRP， anti-CCP， rheumatoid factor （RF）， Th17 and its related cytokines， JAK3， and STAT3 levels in all three groups decreased significantly after treatment （P < 0.05）. Moreover， the above-mentioned indicators in the high-dose group were significantly lower than those in the other two groups after treatment （P < 0.05）. After treatment in the low-dose group， the pain visual analog score， the disease activity score based on ESR of 28 joints， serum Th17 and its related cytokines， JAK3， and STAT3 levels were significantly lower than those in the control group （P < 0.05）. There was no statistically significant difference in the incidence rates of adverse reactions among the three groups （25.00% vs. 15.38% vs. 20.00%） （P > 0.05）. Conclusions The efficacy of high-dose tofacitinib is superior to that of low-dose tofacitinib or etanercept in combination with MTX in the treatment of RRA. It can alleviate clinical symptoms， reduce the levels of serum anti-CCP， Th17-related cytokines， and JAK3/STAT3， without significantly increasing adverse reactions.