Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study

Journal of Drugs in Dermatology, March-April, 2005 by A. Shalita, B. Miller, A. Menter, W. Abramovits, K. Loven, L. Kakita

Abstract

A multicenter, double-blind, randomized, parallel-group trial compared tazarotene 0.1% cream with adapalene 0.1% cream, once daily for 12 weeks, in 173 patients with facial acne vulgaris. Tazarotene was associated with a significantly greater incidence of patients achieving 50% or greater global improvement (77% vs. 55%, P [less than or equal to] .01), and a significantly greater reduction in comedo count (median of 68% vs. 36%, P [less than or equal to] .001, compared with adapalene. A significant between-group difference in baseline inflammatory lesion count precluded a comparison of efficacy against inflammatory acne. The most common adverse events were dryness, peeling/flaking, itching, redness/erythema, burning, and facial irritation with comparable incidences of each between groups. Mean peeling and burning levels were milder with adapalene, though were trace or less in both groups throughout. There were no significant between-group differences in the incidence of patients discontinuing due to lack of efficacy or adverse events. Tazarotene cream offers significantly greater efficacy and comparable tolerability to adapalene cream.

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Introduction

Topical retinoids are the mainstay of treatment for acne vulgaris as they not only offer efficacy against existing acne lesions, but also help prevent the development of new lesions. The therapeutic and preventive actions of topical retinoids result from their ability to help normalize the abnormal desquamation of follicular epithelium in the infrainfundibular portion of the pilosebaceous unit--thereby promoting drainage of microcomedos and comedos. By inhibiting the development of acne at the subclinical microcomedo stage, topical retinoids inhibit the subsequent development of both inflammatory and non-inflammatory acne lesions. Topical retinoids also have some indirect antibacterial activity by virtue of the fact that their actions render the follicular microclimate (biofilm) less hospitable to P. acnes.

Three topical retinoids have been approved by the US Food and Drug Administration for the treatment of acne vulgaris: tretinoin, tazarotene, and adapalene. Initial studies in the 1960s and early 1970s involved tretinoin 0.05% solution and, although efficacy was readily apparent, tolerability was a problem due to significant irritation, erythema, and peeling. Over the years, less irritating formulations of tretinoin have been developed including creams, gels, and, most recently, a microsponge gel. Tazarotene and adapalene were introduced in the 1990s--initially in gel formulations and subsequently in cream formulations (and, for adapalene, in a solution formulation).

In various well-controlled trials directly comparing the gel formulations of these topical retinoids, tazarotene 0.1% gel has shown superior efficacy to tretinoin 0.025% gel, tretinoin 0.1% microsponge gel, and adapalene 0.1% gel, (1-3) with the latter 3 gels generally reported to have comparable efficacy to one another. (4-8) Adapalene gel has a tolerability advantage over the other retinoid gels--although it is important to note that the sensitivity of an individual's skin is at least as important a determinant of tolerability as the individual retinoid applied. (9)

Many patients prefer cream formulations to gel formulations and creams are especially suitable for those with dry or sensitive skin and those living in cold, dry climates. Although several clinical trials have directly compared gel formulations, studies comparing creams are lacking. A multi-center, double-blind, randomized, parallel-group study has recently been performed to compare tazarotene 0.1% cream with adapalene 0.1% cream. To our knowledge, this is the first report comparing cream formulations of different retinoids.

Methods

Patients

Patients were eligible to enroll in this multicenter, double-blind, randomized, parallel-group trial if they had stable facial acne vulgaris--defined as approximately 10 to 60 papules and/or pustules, 10 to 100 open and/or closed comedos, and no more than 5 nodulocystic lesions (of [less than or equal to] 5 mm in diameter) on the face. Patients were also required to be at least 12 years of age and to have conformed to the following washout periods: 14 days for topical acne medications; 30 days for systemic antibiotics and investigational drugs; 12 weeks for estrogens or birth control pills if these had been used for less than 12 weeks (however, patients having used these for more than 12 weeks before entering the study were still eligible for enrollment); and 12 months for oral retinoids.

Exclusion criteria included any patient who had acne vulgaris known to be resistant to oral antibiotics, an uncontrolled systemic disease, was pregnant or breastfeeding, was female and not using a reliable method of contraception, or had any skin disorder that might interfere with the diagnosis or evaluation of acne vulgaris.

The study was approved by the relevant institutional review boards and was performed according to Good Clinical Practice guidelines. All patients gave written informed consent.