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).

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).

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.

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).

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.

痛风性关节炎（GA）是单钠尿酸盐沉积所致的晶体相关性关节病，近年来患病负担持续增加。四妙丸是临床治疗GA的常用中药方剂之一，已被多部相关指南收录或推荐，但其临床获益证据质量及从临床经验、实验研究到临床试验的证据链一致性尚缺乏系统评价。因此，有必要基于整合证据链法和推荐分级的评估、制订和评价（GRADE）系统对四妙丸治疗GA的有效性证据进行再评价。

应用GRADE系统与中药有效性评价整合证据链法（Eff-iEC），对四妙丸治疗痛风性关节炎的有效性证据进行全面、系统的再评价。

计算机检索PubMed、Web of Science、中国知网、维普网、万方数据知识服务平台，检索时限为建库至2025年7月，纳入四妙丸治疗GA的随机对照试验（RCT）、实验研究及临床经验文献，采用Stata 18.0软件进行Meta分析，采用GRADE对结局指标进行证据质量评级，并通过Eff-iEC整合多维度证据。

经筛选文献后，本研究临床经验证据共纳入1篇古籍文献、4篇指南文献；实验研究和临床试验证据分别纳入5篇实验研究、14篇临床试验文献。临床经验证据显示，四妙丸源自"二妙散"化裁，为清热利湿、通痹止痛的经典方剂，自2009年起被纳入《国家基本药物目录》，并被《国际中医临床实践指南　痛风》《痛风及高尿酸血症中西医结合诊疗指南》《痛风和高尿酸血症病证结合诊疗指南》及《高尿酸血症和痛风病证结合诊疗指南》推荐用于治疗GA。Meta分析结果显示，与对照组相比，四妙丸联合常规西医治疗可进一步降低白介素6（IL-6）（6篇文献，n=462，SMD=-1.17，95%CI=-1.59~-0.74，P<0.001）、C反应蛋白（CRP）（5篇文献，n=338，SMD=-0.77，95%CI=-1.12~-0.41，P<0.001）、红细胞沉降率（ESR）（7篇文献，n=477，SMD=-0.96，95%CI=-1.59~-0.34，P=0.002）、肿瘤坏死因子α（TNF-α）（3篇文献，n=240，SMD=-1.84，95%CI=-2.14~-1.54，P<0.001）、视觉模拟评分（VAS）（5篇文献，n=315，SMD=-1.57，95%CI=-2.77~-0.38，P<0.05）及尿酸（UA）水平（10篇文献，n=651，SMD=-1.09，95%CI=-1.57~-0.60，P<0.001），并提高临床有效率（8篇文献，n=576，OR=4.46，95%CI=2.49~8.00，P<0.001）。亚组分析提示，联合用药方案可能是CRP和ESR异质性的重要来源。安全性方面，5篇RCT（400例）报告显示，均未见死亡或严重肝肾功能损害等严重不良事件；观察组不良反应以轻度、可逆事件为主，主要表现为胃肠道反应、头晕及一过性转氨酶升高，发生率为8.0%~23.5%，对照组为4.0%~20.0%。GRADE评价中，四妙丸联合常规西医治疗干预TNF-α、有效率为B级（中等质量证据），IL-6、CRP等指标证据为C级（低质量证据）、ESR、VAS、UA等指标证据为D级（极低质量证据）。Eff-iEC评价中，临床经验证据为A级，实验研究证据为A+级，临床试验证据为B级，综合评定为AA+B（高级证据）。

现有证据表明，四妙丸联合常规西医治疗痛风性关节炎在缓解疼痛、改善炎症反应、降低UA水平及提高临床疗效方面具有一定优势，且短期应用安全性良好。尽管GRADE评价显示当前临床试验证据质量整体偏低，但Eff-iEC评价表明其已形成较完整证据链，综合证据等级为高级。未来仍需开展高质量随机对照试验，以进一步验证其临床获益。