At baseline and week 12, most (≥71%) tazarotene-treated female
and male participants reported ratings of 0 (none) on cutaneous
safety and tolerability evaluations; of participants that had
any signs/symptoms, over 93% reported ratings of 1 (mild) or 2
(moderate; Figure 4). On most assessments, transient increases
in severity (primarily mild or moderate) were found with tazarotene
0.045% at earlier visits (data not shown). By week 12,
however, the percentage of participants reporting “none†were
generally similar to baseline values for most assessments. At
baseline and week 12, no tazarotene-treated male participants
reported ratings of 3 (severe) on any safety or tolerability assessments.
For tazarotene-treated females, a similar number of
severe ratings were reported at baseline and week 12 (baseline,
n=5 total: erythema [n=3], hyperpigmentation and itching [n=1
each]; week 12, n=6 total: burning [n=2], scaling, erythema, hyperpigmentation,
and stinging [n=1 each]).
DISCUSSION
Topical retinoids are widely recommended as first line acne treatment in both men and non-pregnant women but can cause considerable dryness and irritation, limiting their use1 and reducing treatment adherence.17 Tazarotene 0.045% polymeric emulsion lotion was developed to provide a lower-concentration formulation to improve tolerability and penetration of active drug.14 This is accomplished via encapsulation of tazarotene within oil droplets along with hydrating and moisturizing ingredients. The oil droplets are evenly distributed in an oil-and-water emulsion and are separated in a three-dimensional mesh matrix, allowing for uniform dispersion of the oil droplets on the skin.14 In two identical phase 3 randomized studies in participants with moderate-to-severe acne, this lower concentration tazarotene 0.045% lotion was efficacious compared with vehicle and demonstrated a positive safety and tolerability profile.16
Although acne affects both female and male patients, there are differences in disease severity, acne onset (persistent, new, or recurrent), and skin physiology which may impact treatment efficacy, tolerability, or adherence.3,5 As such, the present post hoc analysis was conducted to further explore the efficacy and safety of tazarotene 0.045% lotion by sex. Results demonstrated that tazarotene 0.045% was effective in reducing inflammatory and noninflammatory lesion counts versus vehicle at week 12 in females and males. Significant reductions were observed as early as weeks 4 and 8 in noninflammatory and inflammatory lesion counts, respectively, in both sexes.
While tazarotene 0.045% was efficacious in both females and males, there were some observed differences between the sexes in the present analysis. Reductions in inflammatory and noninflammatory lesions following tazarotene treatment were significantly greater in females than males at nearly all monthly assessments. A greater percentage of tazarotene-treated females also achieved treatment success at week 12 than tazarotene-treated males. Though females had higher responses to tazarotene than males, the separation between tazarotene and vehicle was numerically larger in males at week 12 for both inflammatory and noninflammatory lesion types. The reasons for these results cannot be explained by the current analysis, but differences in terms of compliance (active treatment and/or vehicle) and baseline disease severity may be contributing factors. In addition to being efficacious, tazarotene 0.045% lotion was generally well tolerated in both female and male participants. Although tazarotene-treated females had higher rates of TEAEs compared with tazarotene-treated males, rates of discontinuation due to AEs were low (<4%) in both females and males in either treatment group. The majority of female and male participants reported AE severity as mild. At baseline and week 12, few tazarotene-treated females reported any “severe†ratings for cutaneous safety or tolerability. This may be due to a variety of reasons, including improvement in these ratings over time or a result of participants with moderate or severe ratings dropping out of the study or being less compliant with treatment over time.
The higher TEAE rates and more severe tolerability ratings observed in female participants in this analysis may be due to age differences. On average, the female participants were almost 5 years older than the male participants, with an age range of 10–65 years versus 10–44 for males. Female patients commonly experience dry and sensitive skin,6 especially at older ages when sebum production decreases.5 In addition, older, menopausal females are more likely to experience erythema and hyper- or hypo-pigmentation.6 Even though tazarotene-treated females in the current analysis had higher TEAE rates than males, these rates were similar to those reported in the tazarotene-treated overall population pooled from the two pivotal phase 3 studies (females in current analysis 30.8%; overall pooled population: 26.8%).16 This may be a result of the larger number of female than male participants in the current analysis. Furthermore, rates of application site pain and dryness observed in tazarotene- treated females in this analysis were similar to those seen in the tazarotene-treated overall pooled population (pain, females in the present analysis versus overall population: 6.6% versus 5.3%; dryness: 5.4% versus 3.9%).16
Results from the present analysis demonstrate that the moisturizing, lower-concentration polymeric tazarotene 0.045% lotion was efficacious, safe, and well tolerated for the treatment of moderate-to-severe acne in both female and male participants. Safety and tolerability were more favorable in tazarotene-treated males, although TEAE rates were comparable to rates in the overall population in the two phase 3 trials of tazarotene 0.045% lotion. The females in this analysis were older than the males on average, which may have impacted tolerability due to the changes in skin physiology that occur with aging. Future studies
Although acne affects both female and male patients, there are differences in disease severity, acne onset (persistent, new, or recurrent), and skin physiology which may impact treatment efficacy, tolerability, or adherence.3,5 As such, the present post hoc analysis was conducted to further explore the efficacy and safety of tazarotene 0.045% lotion by sex. Results demonstrated that tazarotene 0.045% was effective in reducing inflammatory and noninflammatory lesion counts versus vehicle at week 12 in females and males. Significant reductions were observed as early as weeks 4 and 8 in noninflammatory and inflammatory lesion counts, respectively, in both sexes.
While tazarotene 0.045% was efficacious in both females and males, there were some observed differences between the sexes in the present analysis. Reductions in inflammatory and noninflammatory lesions following tazarotene treatment were significantly greater in females than males at nearly all monthly assessments. A greater percentage of tazarotene-treated females also achieved treatment success at week 12 than tazarotene-treated males. Though females had higher responses to tazarotene than males, the separation between tazarotene and vehicle was numerically larger in males at week 12 for both inflammatory and noninflammatory lesion types. The reasons for these results cannot be explained by the current analysis, but differences in terms of compliance (active treatment and/or vehicle) and baseline disease severity may be contributing factors. In addition to being efficacious, tazarotene 0.045% lotion was generally well tolerated in both female and male participants. Although tazarotene-treated females had higher rates of TEAEs compared with tazarotene-treated males, rates of discontinuation due to AEs were low (<4%) in both females and males in either treatment group. The majority of female and male participants reported AE severity as mild. At baseline and week 12, few tazarotene-treated females reported any “severe†ratings for cutaneous safety or tolerability. This may be due to a variety of reasons, including improvement in these ratings over time or a result of participants with moderate or severe ratings dropping out of the study or being less compliant with treatment over time.
The higher TEAE rates and more severe tolerability ratings observed in female participants in this analysis may be due to age differences. On average, the female participants were almost 5 years older than the male participants, with an age range of 10–65 years versus 10–44 for males. Female patients commonly experience dry and sensitive skin,6 especially at older ages when sebum production decreases.5 In addition, older, menopausal females are more likely to experience erythema and hyper- or hypo-pigmentation.6 Even though tazarotene-treated females in the current analysis had higher TEAE rates than males, these rates were similar to those reported in the tazarotene-treated overall population pooled from the two pivotal phase 3 studies (females in current analysis 30.8%; overall pooled population: 26.8%).16 This may be a result of the larger number of female than male participants in the current analysis. Furthermore, rates of application site pain and dryness observed in tazarotene- treated females in this analysis were similar to those seen in the tazarotene-treated overall pooled population (pain, females in the present analysis versus overall population: 6.6% versus 5.3%; dryness: 5.4% versus 3.9%).16
Results from the present analysis demonstrate that the moisturizing, lower-concentration polymeric tazarotene 0.045% lotion was efficacious, safe, and well tolerated for the treatment of moderate-to-severe acne in both female and male participants. Safety and tolerability were more favorable in tazarotene-treated males, although TEAE rates were comparable to rates in the overall population in the two phase 3 trials of tazarotene 0.045% lotion. The females in this analysis were older than the males on average, which may have impacted tolerability due to the changes in skin physiology that occur with aging. Future studies
