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

Introduction: 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. Methods: 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. Result: 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], p < 0.00001). The SALT score (MD = -10.09, 95% CI [-12.89, -7.30], p < 0.00001), serum TNF-alpha levels (MD = -0.99, 95% CI [-1.19, -0.39], p < 0.00001), serum IL-12 levels (MD = -8.84, 95% CI [-11.20, -6.47], p < 0.00001) and serum IFN-gamma levels (MD = -7.44, 95% CI [-11.51, -3.37], p = 0.0003) were reduced, and the serum TGF-beta 1 levels (MD = 2.40, 95% CI [1.24, 3.57], p < 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], p = 0.05),' gastrointestinal reactions (RR = 2.47, 95% CI [0.49, 12.55], p = 0.28), lower limb edema (RR = 2.60, 95% CI [0.61, 11.06], p = 0.20), facial edema (RR = 2.33, 95% CI [0.61, 8.93], p = 0.22), or localized itching (RR = 0.56, 95% CI [0.18, 1.75], p = 0.32), between the two groups. Conclusion: 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.