Comparative efficacy and safety of four classical prescriptions for clearing damp-heat recommended by clinical guidelines in treating rheumatoid arthritis: a network meta-analysis.

BACKGROUND: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. METHODS: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. RESULTS: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. DISCUSSION: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.