艾拉莫德联合甲氨蝶呤治疗类风湿关节炎的疗效与安全性：基于随机对照试验的系统评价和Meta分析

The Effect and Safety of Iguratimod Combined With Methotrexate on Rheumatoid Arthritis: A Systematic Review and Meta-Analysis Based on a Randomized Controlled Trial.

作者信息

Zeng Liuting, Yu Ganpeng, Yang Kailin, Hao Wensa, Chen Hua

机构信息

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC-DID), Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China.

Department of Orthopedics, People's Hospital of Ningxiang City, Ningxiang, China.

出版信息

Front Pharmacol. 2022 Jan 18;12:780154. doi: 10.3389/fphar.2021.780154. eCollection 2021.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease with inflammatory synovitis. Iguratimod (IGU) combined with methotrexate (MTX) therapy may have better efficacy and safety. First, we searched randomized controlled trials (RCTs) of IGU + MTX in the treatment of RA through literature databases (such as PubMed, Corkland Library, CNKI, etc.) and then conducted RCT quality assessment and data extraction. Finally, we used RevMan 5.3 for meta-analysis, STATA 15.0 for publication bias assessment, and GRADE tool for the evidence quality assessment of primary outcomes. This systematic review and meta-analysis were registered in PROSPERO (CRD42021220780). This systematic review and meta-analysis included 31 RCTs involving 2,776 patients. Compared with MTX alone, the ACR20, ACR50, and ACR70 of IGU + MTX are higher, while DAS28 is lower [ACR20: (RR 1.55, 95% CI 1.14-2.13, = 0.006); ACR50: (RR 2.04, 95% CI 1.57-2.65, < 0.00001); ACR70: (RR 2.19, 95% CI 1.44-3.34, = 0.00003); DAS28: (weighted mean difference (WMD) -1.65, 95% CI -2.39 to -0.91, < 0.0001)]. Compared with MTX + leflunomide, IGU + MTX has no significant difference in improving ACR20, ACR50, ACR70, but IGU + MTX improves DAS28 more significantly [ACR20: (RR 1.09, 95% CI 0.79-1.89, = 0.59); ACR50: (RR 1.07, 95% CI 0.64-1.78, = 0.81); ACR70: (RR 1.17, 95% CI 0.44-3.10, = 0.76); DAS28: (WMD -0.40, 95% CI -0.42 to -0.38, < 0.0001)]. Compared with the MTX + tripterygium subgroup and MTX-only subgroup, the incidence of adverse events of the IGU + MTX group is of no statistical significance [MTX only: (RR 0.99, 95% CI 0.87-1.13, = 0.90); MTX + Tripterygium: (RR 0.73, 95% CI 0.29-1.85, = 0.50)]. However, compared with MTX + leflunomide, the incidence of adverse events in the IGU + MTX group was lower (RR 0.74, 95% CI 0.62-0.88, = 0.0009). The quality of ACR70 was high; the quality of adverse events and ACR50 test was moderate. Compared with conventional therapy, IGU + MTX may be a safer and more effective therapy for RA patients. When the intervention method is (IGU 25 mg Bid, MTX 10-25 mg once a week), and the intervention lasts for at least 12 weeks, the curative effect may be achieved without obvious adverse events.

类风湿关节炎（RA）是一种伴有炎性滑膜炎的慢性全身性自身免疫性疾病。艾拉莫德（IGU）联合甲氨蝶呤（MTX）治疗可能具有更好的疗效和安全性。首先，我们通过文献数据库（如PubMed、Corkland Library、中国知网等）检索IGU + MTX治疗RA的随机对照试验（RCT），然后进行RCT质量评估和数据提取。最后，我们使用RevMan 5.3进行荟萃分析，使用STATA 15.0进行发表偏倚评估，并使用GRADE工具对主要结局进行证据质量评估。该系统评价和荟萃分析已在国际前瞻性注册系统（PROSPERO，注册号：CRD42021220780）注册。本系统评价和荟萃分析纳入了31项RCT，涉及2776例患者。与单用MTX相比，IGU + MTX的美国风湿病学会20%改善率（ACR20）、ACR50和ACR70更高，而疾病活动度评分28（DAS28）更低[ACR20：（相对危险度（RR）1.55，95%置信区间（CI）1.14 - 2.13，P = 0.006）；ACR50：（RR 2.04，95% CI 1.57 - 2.65，P < 0.00001）；ACR70：（RR 2.19，95% CI 1.44 - 3.34，P = 0.00003）；DAS28：（加权均数差（WMD） - 1.65，95% CI - 2.39至 - 0.91，P < 0.0001）]。与MTX + 来氟米特相比，IGU + MTX在改善ACR20、ACR50、ACR70方面无显著差异，但IGU + MTX在改善DAS28方面更显著[ACR20：（RR 1.09，95% CI 0.79 - 1.89，P = 0.59）；ACR50：（RR 1.07，95% CI 0.64 - 1.78，P = 0.81）；ACR70：（RR 1.17，95% CI 0.44 - 3.10，P = 0.76）；DAS28：（WMD - 0.40，95% CI - 0.42至 - 0.38，P < 0.0001）]。与MTX + 雷公藤多苷亚组和单用MTX亚组相比，IGU + MTX组不良事件发生率无统计学意义[单用MTX：（RR 0.99，95% CI 0.87 - 1.13，P = 0.90）；MTX + 雷公藤多苷：（RR 0.73，95% CI 0.29 - 1.85，P = 0.50）]。然而，与MTX + 来氟米特相比，IGU + MTX组不良事件发生率更低（RR 0.74，95% CI 0.62 - 0.88，P = 0.0009）。ACR70的证据质量高；不良事件和ACR50检验的证据质量为中等。与传统治疗相比，IGU + MTX对RA患者可能是一种更安全、更有效的治疗方法。当干预方法为（IGU 25 mg每日2次，MTX 10 - 25 mg每周1次）且干预持续至少12周时，可能取得疗效且无明显不良事件。