Improved quality of life with effective Treatment of Facial Melasma: the PIGMENT trial

Journal of Drugs in Dermatology, July-August, 2004 by R. Balkrishnan, A.P. Kelly, A. Mcmichael, H. Torok

Abstract/Summary

Melasma is a common hyperpigmentation of the face or neck that can have severe adverse psychological and emotional effects on affected individuals. Although a variety of treatments have been used over the years, results have typically been less than satisfactory. An open-label, community-based trial was undertaken at 393 centers in the United States, enrolling 1290 patients representing a broad range of races/ethnicities and all Fitzpatrick skin types, to evaluate the efficacy and safety of a new melasma treatment that combines fluocinolone acetonide 0.01%, hydroquinone 4.0%, and tretinoin 0.05% (FA HQ RA) in a hydrophilic cream formulation. An additional objective of the study was to assess the impact of this therapy on the quality of life. Efficacy and safety were evaluated at 4 and 8 weeks, and changes in a variety of quality of life parameters were analyzed at the conclusion of the study. All measures of efficacy showed that FA HQ RA significantly (p<0.0001) improved melasma at 4 weeks with further improvement at 8 weeks across all races/ethnicities and Fitzpatrick skin types. The treatment was safe and well tolerated. After 8 weeks of therapy, patients reported that FA HQ RA had provided a variety of benefits that had enhanced their quality of life.

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Melasma is a common acquired hyperpigmentation disorder characterized by irregular tan or brownish macules and patches that occur primarily on the face or neck (1). Although the etiology remains poorly understood, melasma is believed to result primarily from sun exposure and genetic or racial predispositions (2-4). Cosmetics, endogenous and exogenous hormones, pregnancy, and certain drugs have been implicated as well (2).

Melasma can have a severe impact on the quality of life by undermining a patient's psychological and emotional well-being (5). Indeed, individuals with melasma have been described as enduring "great emotional suffering. (3)" The condition is particularly disturbing to patients because of its location on the face (6). Disfiguring facial lesions can lead to decreased social functioning, lowered productivity at work or school, and reduced self-esteem (2,8). In a study using validated instruments developed specifically to measure health-related quality of life in melasma, the three life domains most affected by the condition were social life, recreation and leisure, and emotional well-being (5).

A survey of individuals with hyperpigmentation provided insights into the range of negative emotional reactions related to this skin condition (9). Among the concerns expressed were "People may see me as 'dirty' or 'socially unacceptable,'" "I feel disfigured and deteriorated," "I have to avoid people," and "People focus on my skin and not on me." These findings are notable in view of the fact that one of the strongest independent predictors of reduced health-related quality of life in women with melasma, for example, is an increased fear of negative evaluation by others (5). Additional independent predictors of diminished quality of life include greater disease severity and the belief that life would be better without the condition (5).

Clearly, melasma has broad deleterious effects on quality of life, a fact that underscores the need for effective therapy. Unfortunately, treatment has historically been challenging (2,8-12). Numerous approaches have been used (including depigmentation agents [phenolic and nonphenolic derivatives], chemical peels, topical steroids, laser therapy, cryosurgery, and dermabrasion) (2,3,13-23), but results have often been less than satisfactory. Recently, however, two 8-week, multicenter, randomized trials documented significant improvement in melasma with a new therapy that combines fluocinolone acetonide 0.01%, hydroquinone 4.0%, and tretinoin 0.05% (FA HQ RA) in a hydrophilic cream formulation (Tri-Luma[R] Cream) (2). To gain further insights into the utility of FA HQ RA in the clinical practice setting, an open-label, community-based study was undertaken at a large number of centers. This trial, the Prospective Investigation Gauging Melasma Reduction with a New Treatment (PIGMENT), assessed not only the efficacy and safety of the new formulation, but also its impact on patients' quality of life.

Patients and Methods

The PIGMENT trial was an open-label, community-based Phase IV study conducted at 393 centers in the United States.

Patients

The trial enrolled men and women >18 years of age with moderate to severe melasma of the face. The patients were required to have macular lesions that were neither depressed nor atrophic. All Fitzpatrick skin types (I through VI) were permitted. Women of childbearing potential were eligible for the trial provided they were not pregnant or nursing at the time of enrollment and were using an appropriate method of contraception throughout the study. Informed written consent was obtained from all participants.

Candidates were excluded from participation if they had used any of the following topical preparations or procedures on the face within the preceding two weeks: corticosteroids, glycolic acid, bleaching products, ultraviolet light therapy, or sunbathing, topical retinoids, or medicated or nonmedicated scented cosmetics. Patients were also ineligible for the study if they had used systemic corticosteroids or antibiotics within the preceding four weeks or certain other systemic preparations (acitretin, etretinate, isotretinoin, methotrexate, or photoallergic, phototoxic, or photosensitizing drugs) within the preceding six months. Furthermore, the study excluded patients with any facial skin conditions that would interfere with the trial objectives or evaluations (such as postinflammatory hyperpigmentation, neurodermatitis, eczema, atrophy, or rosacea), were immunocompromised or receiving immunosuppressive medication, had significant endocrine disorders requiring contraindicated treatment with potent corticosteroids, had known sensitivities to any of the ingredients in the trial medication, were unable to avoid more than a minimal amount of sun exposure, had sunbathed recently or regularly or used a tanning salon on a regular basis, or had a history of alcohol or drug abuse.