The Efficacy and Tolerability of Dapsone 5% Gel in Female vs Male PatientsWith Facial Acne Vulgaris: Gender as a Clinically Relevant Outcome Variable

December 2012 | Volume 11 | Issue 12 | Original Article | 1417 | Copyright © December 2012

Emil Tanghetti MD,a Julie C. Harper MDb and Michael G. Oefelein MDc

aCenter for Dermatology and Laser Surgery, Sacramento, CA bThe Dermatology and Skin Care Center of Birmingham, Birmingham, AL cDigiRad Corporation, Poway, CA

Abstract
Background: Gender differences in skin and acne have been reported.
Objective: To evaluate the effect of gender on the efficacy and tolerability of dapsone 5% gel.
Methods: This was a pooled analysis of data from 2 identical phase 3 randomized, double-blind, and vehicle-controlled trials (DAP0203 and DAP0204) of dapsone 5% gel conducted in the United States and Canada between November 2002 and September 2003. A total of 2,898 patients with acne vulgaris were included in the pooled analysis. Of these, 1,453 patients (753 female, 700 male) received dapsone 5% gel twice daily, and 1,445 patients (767 female, 678 male) received vehicle twice daily. End points included the mean percentage reduction from baseline in acne lesion counts and the proportion of patients achieving clinical success (Global Acne Assessment Scale score of 0, clear skin, or 1, almost clear skin). Assessments were performed at baseline and at weeks 2, 4, 6, 8, and 12.
Results: The mean percentage reduction in acne lesion counts at 12 weeks was significantly greater in females than males in both treatment groups. The mean reduction in total lesion counts in dapsone-treated females and males was, respectively, 46.6% vs 35.8% (P<.0001). Reductions in papulopustular and comedonal lesion counts were likewise significantly higher in female than male patients (each P<.0001). Significantly more dapsone-treated females than males achieved clinical success (48.6% vs 34.4%; P=.0003).
Conclusion: The response to dapsone 5% gel appears to be influenced by gender, with female patients experiencing a significantly greater reduction in acne lesion counts and a significantly higher clinical success rate following 12 weeks of treatment. These data suggest that gender is a novel predictor of outcome that should be considered in acne clinical trial design and analysis.

J Drugs Dermatol. 2012;11(12):1417-1421.

INTRODUCTION

Acne is a very common disease that remains prevalent in adults, with more adult women being afflicted than adult men.1 This raises the intriguing possibility that gender differences in skin may influence acne pathogenesis and response to acne treatment. Indeed, gender differences in skin, both its function and structure, have been the focus of considerable research to understand more about skin disease pathogenesis and response to treatment. For example, gender differences in skin surface pH have been reported, although findings have been inconsistent.2-7 It has also been shown that males have thicker skin than females,8 while females have thicker subcutaneous tissues than males.9 Skin thickness tends to decrease with age, especially in women, suggesting that estrogens play a role in maintaining skin.10 Estrogens also have been implicated in regulating the composition of stratum corneum sphingolipids11 and cutaneous protein5 and in decreasing sebum production.12,13 In contrast, androgens appear to increase sebum production,14 possibly by influencing cell proliferation and lipogenesis in the sebaceous gland.14 Sebum production and sebaceous gland activity are major factors in acne lesion development.
Dapsone is an anti-inflammatory agent that, in the 5% gel formulation, is an effective topical treatment for patients with acne vulgaris.15 It has been studied and found to be effective for at least 12 months of treatment16 and to reduce comedonal as well as papulopustular acne lesions when used as monotherapy15 or in combination with a retinoid.17,18 During clinical trials of dapsone 5% gel, some investigators observed a greater acceptance and efficacy of the product in female patients vs in male patients. Given this observation, and previously reported gender differences in skin and acne,19 we explored whether gender impacts the efficacy and tolerability of dapsone 5% gel.

METHODS

Patients, Treatment, and Assessments

The two 12-week, double-blind trials (DAP0203 and DAP0204) enrolled patients 12 years and older with facial acne vulgaris. Patients had 20 to 50 papulopustular lesions and 20 to 100 comedones above the mandibular line at baseline. Other exclusion criteria and study design details are reported in the original study publication.15 Patients were randomized 1:1 to receive either dapsone 5% gel or vehicle gel. Assessments were performed at baseline and at weeks 2, 4, 6, 8, and 12. The following parameters were analyzed and compared in female vs male patients at all time points: the mean percentage reduction from baseline in acne lesion counts (papulopustular, comedonal, and total); the proportion of patients