Randomized, Double-Blinded, Split-Face Study Comparing the Efficacy and Tolerability of Two Topical Products for Melasma

September 2020 | Volume 19 | Issue 9 | Original Article | 822 | Copyright © September 2020

Published online August 24, 2020

Bridget P. Kaufman MD, Andrew F. Alexis MD MPH

Department of Dermatology, Mount Sinai Morningside and Mount Sinai West, New York, NY

Background: Melasma is a common disorder of hyperpigmentation that disproportionately affects individuals with skin of color. There is a paucity of studies evaluating non-hydroquinone (HQ) topical therapies for the treatment of melasma in darker skin types. Objective: To compare the safety, efficacy, and tolerability of a HQ-free, retinol-free cosmetic topical brightener (CTB) and HQ 4% in the treatment of moderate symmetric facial melasma in patients with Fitzpatrick skin types (FST) III–VI. Methods & Materials: This was a randomized, double-blinded, split-face clinical trial. Eighteen adult patients with facial melasma were treated with CTB and HQ 4%, each to a different side of the face, twice daily for 12 weeks. Clinical assessments included half-face Melasma Area Severity Index (MASI), Overall Hyperpigmentation scale, and Melasma Severity Rating Scale (MSRS). Patients completed a Melasma Quality of Life (MelasQoL) questionnaire and clinical photographs were taken at each visit. Results: CTB and HQ 4% demonstrated statistically significant improvements in half-face MASI, Overall Hyperpigmentation, MSRS and MelasQol compared to baseline. HQ 4% showed statistically significant improvements in MSRS at week 12 compared to CTB, but was non-superior for all other clinical endpoints. Conclusion: HQ-free, retinol-free CTB and HQ 4% both are effective and well-tolerated in the treatment of moderate facial melasma in FST III–VI.

J Drugs Dermatol
. 2020;19(9):822-827. doi:10.36849/JDD.2020.5353


Melasma is a common, acquired disorder of skin hyperpigmentation that characteristically presents with symmetric brown macules and patches on the cheeks, forehead, and chin. The highest prevalence is seen in middle-aged females with Fitzpatrick skin types (FST) III-VI, although all racial/ethnic groups can be affected.1-3

The pathogenesis of melasma is multifactorial, with sun exposure, hormonal influences, thyroid disease, and family history, among other factors, leading to alterations in gene expression and molecular signaling within the skin.2-6 This ultimately results in increased melanogenesis, and in some cases melanocytosis, at sites of greater sun exposure and the development of characteristic hyperpigmentation of the skin due to excessive epidermal and dermal melanin deposition.7,8

Successful treatment of melasma often necessitates a multi-modality approach that combines one or more topical agent(s), sun avoidance, and broad-spectrum photoprotection. Procedural treatments including chemical peels and laser/light therapy and treatment with oral tranexamic acid can be considered in refractory cases.9 Hydroquinone (HQ) and Triple Combination Cream containing a retinoid, topical corticosteroid, and HQ (eg, tretinoin 0.05%, fluocinolone acetonide 0.01%, HQ 4%) are currently the gold standard therapies for melasma due to their proven efficacy.9,10 However, their use long-term is limited by potential side effects including exogenous ochronosis (HQ), skin atrophy (corticosteroids), telangiectasias (corticosteroids), irritation and allergic contact dermatitis (HQ, retinoids). Given the chronicity of melasma and its tendency to recur upon cessation of treatment, HQ-free topical therapies are needed for optimal control of the disease.

A HQ-free, retinol-free cosmetic topical brightener (CTB) containing tranexamic acid, phenylethyl resorcinol, niacinamide, and tetrapeptide-30 has been shown to target various melanogenesis pathways, resulting in a more even skin tone and reduced appearance of facial hyperpigmentation in several clinical studies.11-13 In vitro studies of this skin lightening agent using a human tissue model have demonstrated downregulation of micropathalmia transcription factor (MITF), a key regulator of melanocyte activation and melanin production, as well as downstream melanin-synthesizing genes tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1) and DOPAchrome tautomerase (DCT).11 Overall, application of 2 μL of CTB to normal human-derived epidermal keratinocytes and melanocytes was associated with an average melanin