Cost-effectiveness of a fixed combination of hydroquinone/tretinoin/fluocinolone cream compared with hydroquinone alone in the treatment of melasma

Journal of Drugs in Dermatology, Feb, 2007 by Tania Cestari, Lucie Adjadj, Margaret Hux, Maria Regina Shimizu, Vincent Pierre Rives

Abstract

Background: A once-daily fixed combination of hydroquinone, tretinoin, and fluocinolone acetonide (Tri-luma) is a newly available treatment for melasma.

Objective: To assess cost-effectiveness of triple combination therapy (TCT) applied once daily and hydroquinone alone applied twice daily in the US, Argentina, Brazil, Chile, and Colombia from a payer's perspective.

Methods: Clinical data and utilization of key health resources (medication only) were assessed within an 8-week clinical trial conducted in Brazil. Total cost per primary success (complete clearing) was used to compare each treatment with not treating and incremental cost effectiveness ratios were used to compare between treatments.

Results and Conclusion: TCT had a 30% better rate of complete clearing than hydroquinone with a lower cost in the US and an incremental cost in other countries. In every country, cost per primary success was lower for TCT than for hydroquinone. Results were robust to varying assumptions of success rates and quantity used.

Introduction

Melasma is a common acquired hyperpigmentary disorder characterized by dark patches or macules that can involve the cheeks, forehead, upper lip, nose, chin, and neck. (1) Pigmentation may show different distribution patterns (centrofacial, malar, or mandibular) and is characterized primarily by hyperpigmentation in the epidermis, in the lower dermal layer, or a mixed pattern. (1) Ninety percent of patients are female. (2)

Although the etiology of melasma is not completely understood, the most important factors are genetic predisposition, hormonal activity, and sun exposure. In addition to sunlight exposure, which is a large contributor in all cases, genetic predisposition contributes to melasma occurrence more frequently in familial groups and in people of Hispanic, Oriental and Indo-Chinese origin. (3,4,5) Hormonal factors also contribute to the development of melasma. (6) The disease typically affects women in their reproductive years and is often referred to as the "mask of pregnancy" or strongly associated with the use of birth control pills. (3,7-10) Lesions may fade following pregnancy but most frequently persist for long periods of time recurring in subsequent pregnancies.

Although melasma does not pose a medical risk, the overall emotional well being of an individual can be significantly affected, contributing to a decrease in social functioning, productivity at work, and lowered self-esteem. The impact of skin disease on health-related quality of life has been shown with instruments specifically for dermatology such as the Dermatology Life Quality Index (11) and SKINDEX (12,13) or with a tool specifically for melasma like the Melasma Quality of Life (MELASQOL) scale. (14)

Therapy for melasma remains a challenge. The primary pharmaceutical treatment available is the use of topical depigmenting, or bleaching agents applied specifically to pigmented areas. Hydroquinone, azelaic acid, retinoids, and topical corticosteroids have been used as monotherapy or in various combinations. (15) Hydroquinone is the most commonly used treatment for melasma and has been the molecule of reference when treating hyperpigmentary disorders. (15) A phenolic derivative, hydroquinone is thought to work by blocking the synthesis of melanin via the inhibition of tyrosinase and is available in concentrations from 2% to 5%; higher concentrations are more irritating with a modest increase in efficacy. Tretinoin, whose main mechanism of action is increasing turnover of the epidermis, has also been shown to be effective in the treatment of melasma. Although its effectiveness is directly related to strength when used alone, it has poor and slow clinical results at tolerable concentrations: a 4% concentration was found to be very effective but may be a strong irritant. (8,16) Kligman and Willis studied a combination of hydroquinone 5% with tretinoin (0.1%) to facilitate penetration, prevent oxidation of hydroquinone, and stimulate cell turnover, (17) along with a corticosteroid (dexamethasone 0.1%) to reduce irritation and melanin synthesis. They found that a synergy is achieved by the combination of all 3 agents; the triple formulation is more effective than hydroquinone alone or combinations of pairs of the component agents. (18,19)

Vigilant avoidance of sun exposure (both UVA and UVB) including regular use of broad-spectrum sunscreen is a key element for the treatment of melasma.

The first fixed stable combination of hydroquinone, tretinoin, and corticosteroid has recently been made commercially available as a triple combination product, Tri-luma cream. This TCT utilizes the 4% hydroquinone along with 0.05% tretinoin (17) and the middle-low potency corticosteroid fluocinolone acetonide 0.01% (class VI corticosteroid). (20)

Increasingly, treatments are chosen taking into consideration not only clinical safety and effectiveness but also costs associated with alternative treatments. In many countries treatment decision makers including patients, health care providers, and reimbursement groups, are interested in information on costs as well as clinical effects associated with treatments.