Background Gouty arthritis (GA) is a crystal-induced arthropathy caused by monosodium urate deposition, and its disease burden has continued to increase in recent years. Simiao Pill is one of the commonly used traditional Chinese medicine formulas in the clinical treatment of GA and has been included or recommended in multiple relevant guidelines. However, the quality of evidence for its clinical benefits and the consistency of the evidence chain from clinical experience and experimental studies to clinical trials have not yet been systematically evaluated. Therefore, it is necessary to re-evaluate the evidence for the efficacy of Simiao Pill in treating GA based on the integrated evidence chain method and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).
Objective To comprehensively and systematically re-evaluate the evidence for the efficacy of Simiao Pill in the treatment of GA using the GRADE system and the integrated evidence chain based effectiveness evaluation of traditional Chinese medicine (Eff-iEC).
Methods PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), VIP, and Wanfang Data were searched by computer from inception to July 2025. Randomized controlled trials (RCTs), experimental studies, and clinical experience literature on Simiao Pill for GA were included. Meta-analysis was performed using Stata 18.0 software. GRADE was used to rate the quality of evidence for outcome indicators, and multi-dimensional evidence was integrated through Eff-iEC.
Results After literature screening, this study included 1 classical medical literature and 4 guideline documents as clinical experience evidence; 5 experimental studies and 14 clinical trial articles were included as experimental and clinical trial evidence, respectively. Clinical experience evidence showed that Simiao Pill originated from a modified form of"Ermiao San", and is a classic formula for clearing heat, removing dampness, and relieving bi syndrome and pain. Since 2009, it has been included in the National Essential Medicines List and recommended for the treatment of GA by the International Clinical Practice Guideline of Chinese Medicine: Gout, the Guideline for Diagnosis and Treatment of Gout and Hyperuricemia with Integrated Traditional Chinese and Western Medicine, Guideline for Diagnosis and Treatment of Gout and Hyperuricemia Based on TCM Syndromes, and Guideline for Diagnosis and Treatment of Hyperuricemia and Gout. Meta-analysis showed that, compared with the control group, Simiao Pill combined with conventional Western medicine further reduced interleukin-6 (IL-6) (6 articles, n=462, SMD=-1.17, 95%CI=-1.59 to -0.74, P<0.001), C-reactive protein (CRP) (5 articles, n=338, SMD=-0.77, 95%CI=-1.12 to -0.41, P<0.001), erythrocyte sedimentation rate (ESR) (7 articles, n=477, SMD=-0.96, 95%CI=-1.59 to -0.34, P=0.002), tumor necrosis factor-α (TNF-α) (3 articles, n=240, SMD=-1.84, 95%CI=-2.14 to -1.54, P<0.001), Visual Analog Scale (VAS) score (5 articles, n=315, SMD=-1.57, 95%CI=-2.77 to -0.38, P<0.05), and uric acid (UA) level (10 articles, n=651, SMD=-1.09, 95%CI=-1.57 to -0.60, P<0.001), while improving the clinical effective rate (8 articles, n=576, OR=4.46, 95%CI=2.49 to 8.00, P<0.001). Subgroup analysis suggested that the combination regimen may be an important source of heterogeneity for CRP and ESR. Regarding safety, 5 RCTs (400 cases) reported no serious adverse events such as death or severe liver or kidney dysfunction. Adverse reactions in the observation group were mainly mild and reversible, mainly manifested as gastrointestinal reactions, dizziness, and transient elevation of transaminases, with an incidence of 8.0%-23.5%, compared with 4.0%-20.0% in the control group. In the GRADE assessment, TNF-α and effective rate for the intervention of Simiao Pill combined with conventional Western medicine were rated as Grade B (moderate-quality evidence); IL-6 and CRP were rated as Grade C (low-quality evidence); and ESR, VAS, and UA were rated as Grade D (very low-quality evidence). In the Eff-iEC evaluation, clinical experience evidence was rated as Grade A, experimental evidence as Grade A+, and clinical trial evidence as Grade B, with an overall rating of AA+B (high-level evidence).
Conclusion Existing evidence suggests that Simiao Pill combined with conventional Western medicine has certain advantages in treating GA in terms of pain relief, improving inflammatory responses, reducing UA levels, and enhancing clinical efficacy, with good short-term safety. Although GRADE assessment indicates that the overall quality of the current clinical trial evidence is relatively low, Eff-iEC evaluation suggests that a relatively complete evidence chain has been established, and the overall evidence level is high. High-quality randomized controlled trials are still needed in the future to further verify its clinical benefits.
