or adapalene 0.1% or 0.3% in treating acne.9-11 While the efficacy and safety of topical retinoids are well established,12,13 adverse effects such as irritation, erythema, peeling, and dryness can occur in the first weeks of treatment, especially at higher concentrations.7,12 To address these issues, a new tazarotene 0.045% lotion formulation was developed utilizing polymeric emulsion technology.14 An oil-in-water emulsion—structured by a three-dimensional mesh matrix containing tazarotene along with hydrating and moisturizing agents—allows for more uniform release and increased absorption of ingredients. This easily spreadable and easy-to-use lotion formulation also allows for a lower tazarotene concentration, and when combined with optimized delivery of active and hydrating ingredients, may improve tolerability.14
Results from a phase 2 study comparing commercially available tazarotene 0.1% cream or vehicle with the new tazarotene 0.045% lotion demonstrated that tazarotene 0.045% lotion was comparable in efficacy to the higher concentration tazarotene 0.1% cream with fewer treatment-related adverse events.15 Furthermore, data from two identical phase 3 randomized, double-blind, vehicle-controlled, 12-week studies showed tazarotene 0.045% lotion was more efficacious than vehicle and well tolerated in participants with moderate-to-severe acne.16 The objective of this post hoc analysis was to evaluate the safety, efficacy, and tolerability of tazarotene 0.045% lotion in female and male participants with moderate-to-severe acne using data pooled from the two phase 3 trials.
Results from a phase 2 study comparing commercially available tazarotene 0.1% cream or vehicle with the new tazarotene 0.045% lotion demonstrated that tazarotene 0.045% lotion was comparable in efficacy to the higher concentration tazarotene 0.1% cream with fewer treatment-related adverse events.15 Furthermore, data from two identical phase 3 randomized, double-blind, vehicle-controlled, 12-week studies showed tazarotene 0.045% lotion was more efficacious than vehicle and well tolerated in participants with moderate-to-severe acne.16 The objective of this post hoc analysis was to evaluate the safety, efficacy, and tolerability of tazarotene 0.045% lotion in female and male participants with moderate-to-severe acne using data pooled from the two phase 3 trials.
METHODS
Study Design and Participants
Data were pooled from two identical multicenter, randomized, double-blind, vehicle-controlled, parallel-group phase 3 studies (NCT03168321 and NCT03168334), the details of which have been published previously.16 Briefly, patients aged ≥9 years with moderate-to-severe acne (ie, score of 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were eligible to enroll. Patients also had to have 20–50 facial inflammatory lesions (papules, pustules, and nodules), 25–100 noninflammatory lesions (closed and open comedones), and ≤2 facial nodules at the screening visit. Eligible patients were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle lotion to be applied to the face once daily for 12 weeks. CeraVe® hydrating cleanser and moisturizing lotion (L’Oreal, NY) were provided as an option for optimal cleansing and moisturization of the skin.
All studies were conducted in accordance with the International Conference on Harmonization, the Declaration of Helsinki, Good Clinical Practice Guidelines, and local regulations. All participants or their legal guardians provided written informed consent. The studies were approved by the relevant independent ethics committee or institutional review board at each study site.
Efficacy and Safety Assessments
Efficacy assessments comprised investigator-assessed inflammatory and noninflammatory lesion counts and treatment success, defined as the proportion of participants achieving ≥2-grade reduction from baseline in EGSS and a score of 0 or 1; the EGSS is rated on a scale of 0 to 4, where 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe. Study visits included baseline and weeks 4, 8, and 12.
Investigator assessments of cutaneous safety (scaling, erythema, hypopigmentation, hyperpigmentation) were evaluated using a 4-point scale where 0=none; 1=mild; 2=moderate; and 3=severe. Participant evaluations of tolerability (itching, burning, stinging) were reported at all post-screening visits using the same 4-point scale. Adverse events (AEs) were monitored throughout the study.
Statistical Analysis
In each individual phase 3 trial, the co-primary efficacy endpoints were the absolute reductions from baseline to week 12 in inflammatory and noninflammatory lesion counts and the percentage of participants achieving treatment success at week 12. Secondary efficacy endpoints included the percent change in inflammatory and noninflammatory lesion count from baseline to week 12. The intent-to-treat (ITT) population comprised all participants who were randomized and provided with study drug. The safety population consisted of all randomized participants who used study drug or vehicle at least once with a minimum of 1 post-baseline evaluation.
For this pooled post hoc analysis, participants were grouped by sex. Analyses included the percent change from baseline in inflammatory and noninflammatory lesion counts by visit and the percentage of male and female participants achieving treatment success at week 12. For the mean percent changes in inflammatory and noninflammatory lesions, significant skewness was observed. Therefore, a nonparametric method was utilized in which data were rank transformed prior to the analysis of covariance (ANCOVA), with a factor of treatment and the respective baseline lesion count as a covariate. For differences between tazarotene-treated females and males, ranked ANCOVAs with factor of gender and baseline lesion counts as a covariate were used. Treatment success was evaluated via logistic regression using Firth’s Penalized Likelihood, with a factor of treatment group. For all efficacy assessments, multiple imputation was used to impute missing values using the method of Markov Chain Monte Carlo. All statistical analyses were performed using SAS® version 9.3 or later. Statistical significance for tazarotene 0.045% versus vehicle and female versus male were based on two-tailed tests of the null hypothesis resulting in P≤0.05.
Dosing compliance, defined as participants not missing more than 5 consecutive days of dosing and applying 80–120% of ex-
Data were pooled from two identical multicenter, randomized, double-blind, vehicle-controlled, parallel-group phase 3 studies (NCT03168321 and NCT03168334), the details of which have been published previously.16 Briefly, patients aged ≥9 years with moderate-to-severe acne (ie, score of 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were eligible to enroll. Patients also had to have 20–50 facial inflammatory lesions (papules, pustules, and nodules), 25–100 noninflammatory lesions (closed and open comedones), and ≤2 facial nodules at the screening visit. Eligible patients were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle lotion to be applied to the face once daily for 12 weeks. CeraVe® hydrating cleanser and moisturizing lotion (L’Oreal, NY) were provided as an option for optimal cleansing and moisturization of the skin.
All studies were conducted in accordance with the International Conference on Harmonization, the Declaration of Helsinki, Good Clinical Practice Guidelines, and local regulations. All participants or their legal guardians provided written informed consent. The studies were approved by the relevant independent ethics committee or institutional review board at each study site.
Efficacy and Safety Assessments
Efficacy assessments comprised investigator-assessed inflammatory and noninflammatory lesion counts and treatment success, defined as the proportion of participants achieving ≥2-grade reduction from baseline in EGSS and a score of 0 or 1; the EGSS is rated on a scale of 0 to 4, where 0=clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe. Study visits included baseline and weeks 4, 8, and 12.
Investigator assessments of cutaneous safety (scaling, erythema, hypopigmentation, hyperpigmentation) were evaluated using a 4-point scale where 0=none; 1=mild; 2=moderate; and 3=severe. Participant evaluations of tolerability (itching, burning, stinging) were reported at all post-screening visits using the same 4-point scale. Adverse events (AEs) were monitored throughout the study.
Statistical Analysis
In each individual phase 3 trial, the co-primary efficacy endpoints were the absolute reductions from baseline to week 12 in inflammatory and noninflammatory lesion counts and the percentage of participants achieving treatment success at week 12. Secondary efficacy endpoints included the percent change in inflammatory and noninflammatory lesion count from baseline to week 12. The intent-to-treat (ITT) population comprised all participants who were randomized and provided with study drug. The safety population consisted of all randomized participants who used study drug or vehicle at least once with a minimum of 1 post-baseline evaluation.
For this pooled post hoc analysis, participants were grouped by sex. Analyses included the percent change from baseline in inflammatory and noninflammatory lesion counts by visit and the percentage of male and female participants achieving treatment success at week 12. For the mean percent changes in inflammatory and noninflammatory lesions, significant skewness was observed. Therefore, a nonparametric method was utilized in which data were rank transformed prior to the analysis of covariance (ANCOVA), with a factor of treatment and the respective baseline lesion count as a covariate. For differences between tazarotene-treated females and males, ranked ANCOVAs with factor of gender and baseline lesion counts as a covariate were used. Treatment success was evaluated via logistic regression using Firth’s Penalized Likelihood, with a factor of treatment group. For all efficacy assessments, multiple imputation was used to impute missing values using the method of Markov Chain Monte Carlo. All statistical analyses were performed using SAS® version 9.3 or later. Statistical significance for tazarotene 0.045% versus vehicle and female versus male were based on two-tailed tests of the null hypothesis resulting in P≤0.05.
Dosing compliance, defined as participants not missing more than 5 consecutive days of dosing and applying 80–120% of ex-
