Li Shaowei, Liu Dandan, Chen Zhihuang, Wei Song, Xu Wei, Li Xiaohao, Wei Qipeng
Department of Traditional Chinese Medicine, General Hospital of Southern Theater Command of PLA, Guangzhou, China; Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Traditional Chinese Medicine, General Hospital of Southern Theater Command of PLA, Guangzhou, China.
Ann Palliat Med. 2021 Jul;10(7):7298-7328. doi: 10.21037/apm-21-445.
In China, along with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), some herbal formulae for clearing damp-heat are widely applied in treating rheumatoid arthritis (RA). We aimed to summarize and compare the clinical effects of 4 guideline-recommended formulae, including Baihuguizhi decoction, Dangguiniantong decoction, Simiao pill, and Xuanbi decoction.
PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technique Journals (CQVIP), WanFang, and SinoMed (CBM) databases were searched for randomized controlled trials from inception to July 2020 evaluating the efficacy and safety of these recommended herbal formulae combined with 1 csDMARD versus csDMARD alone in RA patients. A pairwise meta-analysis was conducted in RevMan 5.3 software, and a Bayesian network meta-analysis (NMA) was performed with Stata 14.0, R 4.0.2, GeMTC 0.14.3, and JAGS 4.3.0 software. Cochrane Handbook 5.1.0 was used to assess the risk of bias. Publication bias was evaluated using Egger's test, the trim-fill adjustment, and funnel plots. Trial sequential analysis (TSA) was performed to validate the overall results. The rank probability of interventions was calculated and clustered by the surface under the cumulative ranking curve (SUCRA). Pharmacologic actions of formulae were explored through the network pharmacology approach.
A total of 15 studies, including 1,079 individuals, were identified. Simiao pill + csDMARD [SMPPD, odds ratio (OR) =6.62, 95% confidence interval (CI): 2.88 to 16.84] was superior to csDMARDs alone in clinical efficiency, and was more able to reduce C-reactive protein and erythrocyte sedimentation rate levels [mean difference (MD) =-7.91, 95% CI: -17.41 to -1.25; MD =-9.31, 95% CI: -14.48 to -5.56 respectively]. Although publication bias was observed (P=0.033), the trim-fill method indicated that the pooled values kept stable. Fewer adverse events (AEs) were shown with SMPPD (6.45%). TSA confirmed the results of efficacy rate at SMPPD. Network pharmacology included 5 common components and 66 common targets among 4 formulae in treating RA, involving regulating immunity and relieving inflammation.
SMPPD might be a preferable complementary therapy for RA. However, considering the limitations of this study, recommendations for clinical practice should be validated by the results of further well-designed studies.
在中国，除了传统合成改善病情抗风湿药（csDMARDs）外，一些清热利湿的中药方剂也广泛应用于类风湿关节炎（RA）的治疗。我们旨在总结和比较4种指南推荐方剂，包括白虎桂枝汤、当归拈痛汤、四妙丸和宣痹汤的临床疗效。
检索PubMed、Cochrane图书馆、EMBASE、中国知网（CNKI）、维普中文科技期刊数据库（CQVIP）、万方数据库和中国生物医学文献数据库（SinoMed，CBM），查找从建库至2020年7月评估这些推荐中药方剂联合1种csDMARD与单用csDMARD治疗RA患者疗效和安全性的随机对照试验。使用RevMan 5.3软件进行成对荟萃分析，并使用Stata 14.0、R 4.0.2、GeMTC 0.14.3和JAGS 4.3.0软件进行贝叶斯网络荟萃分析（NMA）。采用Cochrane手册5.1.0评估偏倚风险。使用Egger检验、剪补法和漏斗图评估发表偏倚。进行试验序贯分析（TSA）以验证总体结果。通过累积排序曲线下面积（SUCRA）计算并聚类干预措施的排序概率。通过网络药理学方法探索方剂的药理作用。
共纳入15项研究，涉及1079例患者。四妙丸+csDMARD [SMPPD，优势比（OR）=6.62，95%置信区间（CI）：2.88至16.84]在临床疗效上优于单用csDMARDs，且更能降低C反应蛋白和红细胞沉降率水平[平均差（MD）=-7.91，95%CI：-17.41至-1.25；MD=-9.31，95%CI：-14.48至-5.56]。尽管存在发表偏倚（P=0.033），但剪补法表明合并值保持稳定。SMPPD显示的不良事件（AE）较少（6.45%）。TSA证实了SMPPD的有效率结果。网络药理学研究发现4种方剂治疗RA有5种共同成分和66个共同靶点，涉及调节免疫和减轻炎症。
SMPPD可能是RA较好的辅助治疗方法。然而，考虑到本研究的局限性，临床实践建议应通过进一步精心设计的研究结果进行验证。
