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
Gender differences in skin and acne have been reported.
To evaluate the effect of gender on the efficacy and tolerability of dapsone 5% gel.
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.
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).
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.
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.
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