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（China National Knowledge Infrastructure, CNKI）、万方（Wanfang）以及维普（VIP）数据库。纳入对比复方甘草酸苷联合外用米诺地尔与单用外用米诺地尔治疗斑秃的随机对照试验（randomized controlled trial, RCT）。采用Cochrane协作网偏倚风险评估工具对纳入研究的偏倚风险进行评价。统计学分析采用RevMan5.3软件与Stata 15.0软件完成。采用GRADE系统对结局指标的证据质量进行评价。最终纳入11项随机对照试验，共计1189例患者。与单用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更有效地提升临床疗效（相对危险度（Relative Risk, RR）=1.36，95%置信区间（Confidence Interval, CI）[1.27, 1.45]，p<0.00001）。斑秃严重程度评分（Severity of Alopecia Tool, SALT）（均数差（Mean Difference, MD）=-10.09，95%CI[-12.89, -7.30]，p<0.00001）、血清肿瘤坏死因子-α（Tumor Necrosis Factor-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（Interleukin-12, IL-12）水平（MD=-8.84，95%CI[-11.20, -6.47]，p<0.00001）以及血清干扰素-γ（Interferon-γ, IFN-γ）水平（MD=-7.44，95%CI[-11.51, -3.37]，p=0.0003）均显著降低，而血清转化生长因子-β1（Transforming Growth Factor-β1, TGF-β1）水平（MD=2.40，95%CI[1.24, 3.57]，p<0.0001）显著升高。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）以及局限性瘙痒（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。