The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210023, China.
Department of Diabetes and Cancer Metabolism, City of Hope National Medical Center, Duarte, CA 91010, USA.
Pharmacol Res. 2022 Oct;184:106405. doi: 10.1016/j.phrs.2022.106405. Epub 2022 Aug 24.
To explore efficacy and safety, as well as efficacy mechanisms, main efficacy characteristics, and efficacy influencing factors of TG, in combination with one conventional DMARD, to provide guidance for the clinical application of TG in treating RA.
We searched the databases of PubMed, Embase, Web of Science, Cochrane Library, Ovid, Scopus, Clinicaltrials.gov, CNKI, Wanfang, SinoMed, VIP, Chinese Clinical Trial Registry, KTKP, and J-STAGE to August 12, 2022. All included studies were analyzed with Stata 16.0 software and Review Manager 5.4 software according to the PRISMA Statement.
Thirty-eight randomized controlled trials (RCTs) were included. Combined TG was superior in 28-joint count Disease Activity Score (DAS28) and American College of Rheumatology 50 response (ACR50) and did not increase adverse events (AEs). Combined TG significantly suppressed interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α). And combined TG showed significant advantages in improving tender joint count (TJC), swollen joint count (SJC), pain score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and physician's and patient's global assessments of disease activity. However, the average age of the intervention population, treatment course, the combined DMARDs category, and the risk of bias were important factors influencing the above effects.
The combination of TG is superior to conventional DMARD monotherapy in improving RA conditions with a good safety profile. This effect is closely related to the mechanism of TG reducing IL-1, IL-6 and TNF-α. And the combination of TG shows better effect in all aspects such as improving joint signs, symptoms, inflammatory indicators, and overall health. But for those under 45 years of age, with short-term intermittent dosing, in combination with MTX may be more beneficial for TG to show better efficacy.
探讨替格瑞洛（TG）联合一种常规改善病情抗风湿药（DMARD）的疗效和安全性，以及作用机制、主要疗效特点和疗效影响因素，为 TG 治疗 RA 提供临床应用指导。
计算机检索 PubMed、Embase、Web of Science、Cochrane 图书馆、Ovid、Scopus、Clinicaltrials.gov、中国知网（CNKI）、万方、维普、中国临床试验注册中心（ChiCTR）、韩国临床试验注册平台（KTKP）和日本临床试验注册平台（J-STAGE），检索时限均为建库至 2022 年 8 月 12 日。根据 PRISMA 声明对纳入的研究进行资料提取和质量评价后，采用 Stata 16.0 软件和 Review Manager 5.4 软件进行 Meta 分析。
共纳入 38 项 RCT。TG 联合组在 28 个关节疾病活动度评分（DAS28）和美国风湿病学会 50 应答（ACR50）方面均优于 DMARD 单药组，且不增加不良反应。TG 联合组可显著抑制白细胞介素-1（IL-1）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）。TG 联合组在改善压痛关节数（TJC）、肿胀关节数（SJC）、疼痛评分、红细胞沉降率（ESR）、C 反应蛋白（CRP）、医生和患者整体评估疾病活动度方面均具有显著优势。但干预人群的平均年龄、疗程、联合 DMARD 种类和偏倚风险是影响以上结局的重要因素。
TG 联合方案在改善 RA 病情方面优于 DMARD 单药治疗，且安全性良好。这种疗效与 TG 降低 IL-1、IL-6 和 TNF-α的作用机制密切相关。且在改善关节体征、症状、炎症指标和整体健康等各方面，TG 联合方案均具有更好的效果。但对于年龄<45 岁、短期间歇性给药、联合 MTX 的患者，可能更有利于 TG 发挥更好的疗效。
