Evaluating the Efficacy, Safety, and Tolerability of the Combination of Tazarotene, Azelaic Acid, Tacrolimus, and Zinc Oxide for the Treatment of Melasma: A Pilot Study.

Background: Melasma is a common hyperpigmentation disorder of the skin. Combination therapy of topical retinoids, corticosteroids, and hydroquinone has been effective in treating melasma, but long-term use is limited by corticosteroid atrophy and exogenous ochronosis. The aim of this pilot study (NCT02730819) was to determine the efficacy, safety, and tolerability of a novel composition (2013-MCN-333) comprising tazarotene 0.075%, azelaic acid 20%, tacrolimus 0.1%, and (microfine) zinc oxide 10% for the treatment of melasma. Methods: Sixteen patients with moderate-to-severe melasma were treated daily with sunscreen and 2013-MCN-333 for 20 weeks. Primary outcome measure was change in Melasma Area and Severity Index (MASI) score. Results: Twenty-five percent of patients met the primary endpoint of a MASI score of less than eight points at Week 20. MASI score also decreased significantly from baseline (median: 18.9 points) through Week 4 (median: 17.3 points; p=0.006), Week 12 (median: 16.0 points; p=0.001), and Week 20 (median: 13.3 points; p=0.001). Treatment-related adverse events were mild, most of which decreased or resolved over the course of the study. Limitations: The small sample size and nonblinded nature of treatment intervention are potential limitations. Conclusion: Our results suggest daily 2013-MCN-333 could potentially be an effective, safe, and tolerable treatment for moderate-to-severe melasma.