Efficacy and safety of compound glycyrrhizin combined with topical minoxidil for alopecia areata: a systematic review and meta-analysis of randomized controlled trials

Alopecia areata (AA) is a common autoimmune skin disease. Our study aimed to systematically evaluate the efficacy and safety of compound glycyrrhizin (CG) combined with topical minoxidil therapy in treating AA. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases. Randomized controlled trials (RCTs) on CG combined with topical minoxidil therapy compared with topical minoxidil therapy alone for AA were included. The Cochrane Collaborative Network Tool was used to assess the risk of bias. Statistical analysis was completed using RevMan5.3 software and Stata 15.0 software. The GRADE system was used to evaluate the quality of evidence for outcomes. 11 RCTs and 1189 patients were included. Compared with topical minoxidil therapy alone, CG combined with topical minoxidil therapy was more effective at improving the clinical efficacy (RR = 1.36, 95% CI [1.27, 1.45], <i>p</i> &lt; 0.00001). The SALT score (MD = −10.09, 95% CI [−12.89, −7.30], <i>p</i> &lt; 0.00001), serum TNF-α levels (MD = −0.99, 95% CI [−1.19, −0.39], <i>p</i> &lt; 0.00001), serum IL-12 levels (MD = −8.84, 95% CI [−11.20, −6.47], <i>p</i> &lt; 0.00001) and serum IFN-γ levels (MD = −7.44, 95% CI [−11.51, −3.37], <i>p</i> = 0.0003) were reduced, and the serum TGF-β1 levels (MD = 2.40, 95% CI [1.24, 3.57], <i>p</i> &lt; 0.0001) were increased. There were no significant differences in reported adverse events, including irritant contact dermatitis (RR = 0.51, 95% CI [0.25, 1.01], <i>p</i> = 0.05),’ gastrointestinal reactions (RR = 2.47, 95% CI [0.49, 12.55], <i>p</i> = 0.28), lower limb edema (RR = 2.60, 95% CI [0.61, 11.06], <i>p</i> = 0.20), facial edema (RR = 2.33, 95% CI [0.61, 8.93], <i>p</i> = 0.22), or localized itching (RR = 0.56, 95% CI [0.18, 1.75], <i>p</i> = 0.32), between the two groups. The current evidence indicates that CG combined with topical minoxidil therapy is effective and safe for AA. However, owing to the suboptimal quality of the included studies, more high-quality and large-scale RCTs are needed for comprehensive analysis and further validation.

斑秃（Alopecia areata, AA）是一种常见的自身免疫性皮肤病。本研究旨在系统评价复方甘草酸苷（Compound glycyrrhizin, CG）联合外用米诺地尔治疗斑秃的疗效与安全性。
我们检索了PubMed、EMBASE、Cochrane图书馆、Web of Science、中国知网（CNKI）、万方数据知识服务平台、维普资讯数据库。纳入比较复方甘草酸苷联合外用米诺地尔与单纯外用米诺地尔治疗斑秃的随机对照试验（Randomized controlled trials, RCTs）。采用Cochrane协作网偏倚风险评估工具评价偏倚风险，使用RevMan5.3软件与Stata 15.0软件完成统计分析，采用GRADE系统评价结局证据质量。
本研究共纳入11项随机对照试验，涉及1189例患者。与单纯外用米诺地尔治疗相比，复方甘草酸苷联合外用米诺地尔可显著提升临床疗效（相对危险度RR=1.36，95%置信区间CI[1.27, 1.45]，p<0.00001）；可降低SALT评分（均差MD=-10.09，95%CI[-12.89, -7.30]，p<0.00001）、血清肿瘤坏死因子α（TNF-α）水平（MD=-0.99，95%CI[-1.19, -0.39]，p<0.00001）、血清白细胞介素12（IL-12）水平（MD=-8.84，95%CI[-11.20, -6.47]，p<0.00001）及血清干扰素γ（IFN-γ）水平（MD=-7.44，95%CI[-11.51, -3.37]，p=0.0003），同时升高血清转化生长因子β1（TGF-β1）水平（MD=2.40，95%CI[1.24, 3.57]，p<0.0001）。两组报告的不良事件，包括刺激性接触性皮炎（RR=0.51，95%CI[0.25, 1.01]，p=0.05）、胃肠道反应（RR=2.47，95%CI[0.49, 12.55]，p=0.28）、下肢水肿（RR=2.60，95%CI[0.61, 11.06]，p=0.20）、面部水肿（RR=2.33，95%CI[0.61, 8.93]，p=0.22）及局部瘙痒（RR=0.56，95%CI[0.18, 1.75]，p=0.32），组间差异均无统计学意义。
现有证据表明，复方甘草酸苷联合外用米诺地尔治疗斑秃安全有效。但由于纳入研究的质量欠佳，仍需开展更多高质量、大样本的随机对照试验以进行全面分析与进一步验证。