Adapalene 0.1% gel compared to tazarotene 0.1% cream in the treatment of acne vulgaris

Journal of Drugs in Dermatology, June, 2008 by David Pariser, Luz E. Colon, Lori A. Johnson, Ronald W. Gottschalk

Abstract

A variety of topical retinoids is available for the treatment of acne vulgaris. Selection of the appropriate treatment depends not only on efficacy but also on how well the patient can tolerate different formulations. The goal of this study was to evaluate the efficacy and tolerability of daily adapalene 0.1% gel compared to daily tazarotene 0.1% cream and to demonstrate the noninferiority of adapalene 0.1% gel when compared to tazarotene 0.1% cream in treating acne. This represents 2 arms of a3-arm study. Subjects 12 to 35 years of age with acne vulgaris (N=202) participated in a 12-week, randomized, evaluator-blinded study of once-daily therapy with adapalene 0.1% gel versus tazarotene 0.1% cream. The primary measure of efficacy was the reduction in total lesion counts posttreatment. Subjects treated with adapalene 0.1% gel achieved similar reductions in total lesion counts at week 12 compared to the subjects treated with the tazarotene cream, which demonstrates the noninferiority of adapalene treatment compared to tazarotene (median difference: -1.18%; lower confidence limit [LCL]: -9.26). At week 2, the number of patients that experienced erythema and scaling with tazarotene 0.1% cream was greater when compared to adapalene 0.1% gel. and statistically significant. By week 12, the percentage of subjects reporting cutaneous irritation had returned to or near baseline levels and was similar between treatment arms for all parameters assessed. Adapalene gel was associated with fewer treatment-related adverse events than tazarotene cream (36% versus 58%, respectively), and less than half as many adverse events that were "definitely" related to study treatment than tazarotene cream (20% versus 45%, respectively). Daily therapy with adapalene 0.1% gel was shown to be noninferior to tazarotene 0.1% cream in total acne lesion reductions, and during initial stages of treatment, demonstrated better tolerability with respect to erythema and scaling.

Introduction

Acne vulgaris is the most common skin condition seen by physicians and one of the main reasons young people consult a physician. (1), (2) The pathogenesis of acne is complex and involves at least 4 distinct events within pilosebaceous hair follicles, namely increased sebum production, increased epithelial cell turnover, colonization by Propionibacterium acnes (P acnes), and release of inflammatory mediators into the follicle and surrounding dermis. (3), (4) Treatment strategies that simultaneously target more than one of these mechanisms are believed to be the most effective for clearing existing lesions and preventing recurring lesions. (5)

For all forms of acne except the most severe, recommended treatment strategies include topical retinoids, either alone or in combination with other medications, as first-line therapies. (5-7) Topical retinoids are thought to reverse abnormal desquamation in the follicle by reducing epithelial turnover and also may exert and-inflammatory effects by modulating the skin's immune response. (6) It has been theorized that topical retinoids may also facilitate the penetration of other compounds, such as benzoyl peroxide and topical antibiotics, to reduce P acnes proliferation. (8)

Topical retinoids, such as adapalene and tazarotene, are available in both cream and gel formulations. Many dermatologists believe that minimizing skin irritation is key to maintaining patient compliance and thus the choice of a gel or cream formulation is important. (5) Comparisons of the efficacy and tolerability of the gel formulations of adapalene and tazarotene have been previously reported (9), (10) but a direct comparison of adapalene 0.1% gel to tazarotene 0,1% cream has not been performed. This comparison is important since according to Wolters Kluwer Health, 37.5% of all dispensed tazarotene prescriptions in 2006 were for the 0.1 % cream formulation, compared to 15.9% for the 0.1% gel formulation. (11)

A randomized multicenter study was designed to analyze adapalene 0.1% gel compared to tazarotene 0.1% cream for effectiveness and tolerability in reducing total acne lesion counts following 12 weeks of daily treatment. Subjects were randomized to 1 of 3 treatment arms and treated with adapalene 0.1% gel, tazarotene 0.1% cream, or adapalene 0.1% gel for 6 weeks followed by tazarotene 0.1% cream for 6 weeks (switch arm). Data from the noninferiority comparison between 2 of the 3 arms, adapalene 0.1% gel arm and tazarotene 0.1% cream arm, were analyzed.

Methods

The study was a phase 4, randomized, controlled, evaluator-blind, parallel-arm, multicenter trial designed to evaluate and compare the efficacy and safety of adapalene 0.1% gel once daily for 12 weeks (adapalene 0.1% gel arm) to tazarotene 0.1% cream once daily for 12 weeks (tazarotene 0.1% cream arm) for the treatment of acne vulgaris.

The target enrollment was 100 male and female subjects per treatment arm. For inclusion, subjects had to be between 12 and 35 years of age, with 15 to 100 noninflammatory lesions, at least 20 inflammatory lesions, and not more than 3 nodulocystic lesions. Exclusion criteria included subjects with severe nodulocystic acne, female subjects who were or planning to become pregnant during the study or nursing, subjects with facial hair that would impair study assessments, subjects with washout periods less than 4 weeks for topical acne treatments or less than 6 months for systemic therapy, or subjects with other dermatologic conditions with which treatment may interfere. Treatment was assigned according to a computer-generated randomization scheme and evaluations were performed at baseline, weeks 2, 6, 8, and 12.