2022 年第 9 期 第 17 卷

托法替布在甲氨蝶呤应答不足成人类风湿关节炎中的疗效及引起的并发症分析

Efficacy and complications of tofacitinib in rheumatoid arthritis in adults with inadequate methotrexate response

作者：徐蓓陈竹

英文作者：Xu Bei Chen Zhu

单位：中国科学技术大学附属第一医院（安徽省立医院）风湿免疫科，合肥230036

英文单位：Department of Rheumatism and Immunology Anhui Provincial Hospital the First Affiliated Hospital of University of Science and Technology of China Hefei 230036 China

关键词：类风湿关节炎；托法替布；甲氨蝶呤

英文关键词：Rheumatoidarthritis;Tofacitinib;Methotrexate

• 摘要：

• 目的 探讨托法替布在甲氨蝶呤应答不足成人类风湿关节炎（RA）中的疗效及引起的并发症。方法  纳入2019年1月至2022年1月中国科学技术大学附属第一医院收治的甲氨蝶呤应答不足成人RA患者82例，根据随机数字表法分成托法替布组与雷公藤组，各41例。雷公藤组采用雷公藤多苷20 mg/次，3次/d口服治疗。托法替布组采用托法替布5 mg/次，2次/d口服治疗。2组至少治疗12周。比较2组治疗前和治疗8、12周后的疗效指标，包括关节压痛数、关节肿胀数以及28个关节疾病活动评分（DAS28）、临床疾病活动指数（CDAI）、简化疾病活动指数（SDAI）以及红细胞沉降率（ESR）、C反应蛋白（CRP）、白细胞介素10（IL-10）、IL-17、肿瘤坏死因子α（TNF-α）水平。比较2组因药物引起的不良事件发生率。结果  治疗8、12周后，2组关节压痛数、关节肿胀数、DAS28、CDAI、SDAI均低于治疗前，且托法替布组均低于雷公藤组［治疗8周后：（7.6±2.7）个比（10.5±2.3）个、（6.1±1.6）个比（8.3±1.6）个、（4.4±0.3）分比（4.8±0.6）分、（23.6±4.2）分比（26.7±2.8）分、（24.6±4.3）分比（28.4±3.7）分；治疗12周后：（3.9±1.2）个比（7.4±1.6）个、（2.7±1.0）个比（6.6±1.4）个、（3.1±0.9）分比（4.4±0.8）分、（11.5±3.2）分比（17.3±2.7）分、（13.6±2.7）分比（20.6±4.5）分］（均P＜0.05）。治疗8、12周后，2组ESR、CRP、IL-17、TNF-α水平均低于治疗前，IL-10水平均高于治疗前，且托法替布组ESR、CRP、IL-17、TNF-α水平均低于雷公藤组，IL-10水平均高于雷公藤组（均P＜0.05）。治疗12周期间，2组均未引起严重并发症，托法替布组不良事件发生率与雷公藤组比较差异无统计学意义［17.1%（7/41）比14.6%（6/41）］（P=0.762）。结论 针对甲氨蝶呤应答不足的成人RA患者给予托法替布治疗，能取得良好效果，可进一步减轻炎症反应，且安全性较高。

• Objective  To investigate the efficacy and complications of tofacitinib in adult rheumatoid arthritis (RA) with inadequate methotrexate response. Methods  Totally 82 adult RA patients with inadequate methotrexate response were enrolled in the First Affiliated Hospital of University of Science and Technology of China from January 2019 to January 2022. They were divided into tofacitinib group and tripterygium group, with 41 cases in each group, according to the random number table method. Tripterygium group was treated with Tripterygium wilfordii polyglycoside orally, 20 mg/time, 3 times per day. The tofacitinib group was treated with tofacitiniborally, 5 mg/time, twice a day. The two groups were treated for at least 12 weeks. The efficacy indexes of the two groups were compared before treatment and 8 and 12 weeks after treatment, including the number of joint tenderness and joint swelling, 28 joint disease activity scores (DAS28), clinical disease activity index (CDAI), simplified disease activity index (SDAI), levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), interleukin-10 (IL-10), IL-17, and tumor necrosis factor-α（TNF-α）. The incidence of adverse events caused by drugs was compared between the two groups. Results  After 8 and 12 weeks of treatment, the number of joint tenderness and joint swelling, DAS28 score, CDAI score and SDAI score in the two groups were lower than those before treatment, and those in the tofacitinib group were lower than those in the tripterygium group ［8 weeks after treatment: (7.6±2.7) vs (10.5±2.3), (6.1±1.6) vs (8.3±1.6), (4.4±0.3) vs (4.8±0.6), (23.6±4.2) vs (26.7±2.8), (24.6±4.3) vs (28.4±3.7); 12 weeks after treatment: (3.9±1.2) vs (7.4±1.6), (2.7±1.0) vs (6.6±1.4), (3.1±0.9) vs (4.4±0.8), (11.5±3.2) vs (17.3±2.7), (13.6±2.7) vs (20.6±4.5)］ (all P＜0.05). After 8 and 12 weeks of treatment, the levels of ESR, CRP, IL-17 and TNF-α in the two groups were lower than those before treatment, the levels of IL-10 were higher than those before treatment, the levels of ESR, CRP, IL-17, TNF-α in the tofacitinib group were lower than those in the tripterygium group, and the levels of IL-10 in the tofacitinib group were higher than those in the tripterygium group (all P＜0.05). During the 12 weeks of treatment, no serious complications were caused in both groups. There was no significant difference in the incidence of adverse events between the tofacitinib group and the tripterygium group［17.1%(7/41) vs 14.6%(6/41)］(P=0.762). Conclusion  Tofacitinib has good effect on adult RA patients with inadequate methotrexate response, which can further reduce inflammatory response with high safety.