Comparative Efficacy and Safety of Injectable Tranexamic Acid Combination Therapies for Melasma: A Network Meta-analysis of Randomized Controlled Trials

Melasma is a challenging hyperpigmentation disorder affecting predominantly women with darker skin tones. Despite various treatments, achieving consistent and effective results remains difficult. Tranexamic acid (TXA) has emerged as a promising therapeutic agent, particularly through intradermal injections, but its optimal concentration, delivery method, and combination therapies remain unclear. In this study, the authors aim to evaluate the efficacy and safety of injectable TXA, focusing on its use alone and in combination with other treatments, such as hydroquinone, for melasma. A network meta-analysis of 9 randomized controlled trials was conducted, involving 358 participants. Data on melasma subtype, TXA concentration, delivery method, and treatment outcomes (Melasma Area and Severity Index [MASI] scores) were extracted. Statistical analysis was performed using a random-effects model, assessing both direct and indirect comparisons. The combination of TXA and 4% hydroquinone showed the most significant improvement in MASI scores compared with other interventions, demonstrating superior efficacy. Adverse effects were mild and transient, including injection-site pain and erythema, underscoring a favorable safety profile. Injectable TXA, especially in combination with hydroquinone, is an effective treatment for melasma. Standardized protocols and long-term studies are needed to optimize its use. Level of Evidence: 3 (Therapeutic).