Retrospective Evaluation of the Efficacy and Tolerability of a Combination Cream Containing 3% Kojic Acid, 10% Liposomal Azelaic Acid, 1% Tranexamic Acid, 3% Glycolic Acid, and 1.5% 4-n-Butylresorcinol for the Treatment of Melasma

BackgroundMelasma is a chronic acquired hyperpigmentary disorder characterized by symmetrical facial pigmentation and substantial psychosocial impact.Despite available treatments, outcomes remain variable, highlighting the need for therapies targeting multiple melanogenesis pathways.This study evaluated the clinical effectiveness, safety, and patient satisfaction of a combination cream containing 3% kojic acid, 10% liposomal azelaic acid, 1% tranexamic acid, 3% glycolic acid, and 1.5% 4-n-butylresorcinol in patients with melasma. MethodsThis retrospective, multicenter observational study included 3,090 patients with melasma treated across 383 dermatology centers in routine practice.Baseline demographic and disease characteristics were extracted from medical records.Clinical effectiveness was assessed by changes in the Melasma Severity Scale at one and two months.Secondary outcomes included physician-and patient-reported satisfaction and safety.Longitudinal changes were analyzed using generalized estimating equations with an ordinal multinomial distribution and cumulative logit link; subgroup associations were evaluated using chi-square tests with Cramér's V. ResultsThe mean age of the 3,090 patients was 34.38 ± 7.20 years, and 1,981 (64.1%) were female.The mean disease duration was 17.56 ± 14.53 months.Melasma severity progressively improved during treatment, with mean score changes of -0.42 ± 0.76 at one month and -1.01 ± 1.23 at two months.Clinical improvement was observed in 1,443 (46.7%) patients at one month and 2,086 (67.5%) patients at two months.Severity scores improved significantly over time (p < 0.001), with progressive shifts toward lower severity categories.Treatment response was significantly associated with baseline clinical characteristics, including Fitzpatrick skin type, melasma subtype, disease duration, and lesion distribution (p < 0.001).At two months, 1,343 (43.5%) patients had minimal residual disease on physician assessment, while 180 (5.8%) patients remained severely affected.Patient and physician satisfaction was high, and the treatment was generally well tolerated, with predominantly mild local adverse reactions and minimal treatment discontinuation. ConclusionIn this large real-world study, the combination cream produced significant, progressive improvement in melasma severity with a clear time-dependent effect and high patient and physician satisfaction.Treatment response varied by baseline characteristics, with greatest benefit in Fitzpatrick skin types V-VI.Despite mild local adverse reactions, the formulation containing 3% kojic acid, 10% liposomal azelaic acid, 1% tranexamic acid, 3% glycolic acid, and 1.5% 4-n-butylresorcinol demonstrated favorable safety and tolerability, supporting its use as a multi-mechanistic topical therapy for melasma.