to-severe acne, once-daily treatment with tazarotene 0.045% lotion significantly reduced inflammatory and noninflammatory lesions relative to vehicle lotion.6 Both studies included the 19-item Acne-Specific Quality of Life questionnaire (Acne- QoL),7 which showed improvements in patient-reported quality of life with tazarotene 0.045% lotion after 12 weeks of treatment. Given the psychosocial impact of acne on quality of life,8,9 post hoc analyses of the phase 3 data were conducted to evaluate which aspects of the Acne-QoL were of greatest concern to study participants and the effects of tazarotene 0.045% on those domains.
METHODS
Study Design
Detailed methods for the two phase 3 studies (NCT03168334 and NCT03168321) have been reported.6 In brief, both were multicenter, double-blind, randomized, vehicle-controlled, parallel group phase 3 studies. Key eligibility criteria included: male or female, age 9 years or older; moderate or severe acne (Evaluator's Global Severity Score [EGSS] of 3 or 4); 20–50 facial inflammatory lesions (papules, pustules, and nodules); 25–100 noninflammatory lesions (open and closed comedones); and ≤2 facial nodules. Eligible patients were randomized 1:1 to receive tazarotene 0.045% lotion or vehicle, applied oncedaily to the face 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. The study protocol was approved by institutional review boards or ethics committees at all investigational sites. Studies were carried out in accordance with principles of Good Clinical Practice (GCP) and the Declaration of Helsinki. All patients or their legal guardians provided written informed consent.
Quality of Life Assessment
Quality of life was assessed using the Acne-QoL, which includes 19 items in 4 different domains: self-perception (items 1, 2, 3, 6, and 10); role-emotional (items 4, 5, 7, 8, and 9), role-social (items 11, 12, 13, and 14), acne symptoms (items 15, 16, 17, 18, and 19). For each item, participants were asked to rate the degree to which acne has affected them with a score of 0 (“extremely”) to 6 (“not at all”). Higher scores indicated better quality of life, and a positive score change indicated improvement.
Post Hoc Analyses
All analyses were based on the pooled intent-to-treat (ITT) population, defined as randomized participants who were provided with study drug. Mean changes from baseline to week 12 in Acne- QoL domain and item scores were analyzed in the pooled ITT population using an analysis of covariance (ANCOVA) with treatment group as a factor and baseline score as a covariate; P<0.05 indicated statistical significance between tazarotene 0.045% lotion and vehicle lotion. The ANCOVA model was also used to investigate Acne-QoL outcomes in participants categorized by EGSS score at baseline (score of 3 [moderate acne symptoms] or 4 [severe acne symptoms]) and by median Acne-QoL total score at baseline in the pooled ITT population (score ≥60 [better quality of life] or <60 [worse quality of life]).
Because differences in sex and race had been observed between the EGSS subgroups and between the Acne-QoL subgroups, exploratory analyses were conducted in demographic subgroups. Mean changes from baseline to week 12 in Acne-QoL domain scores were analyzed descriptively in tazarotene-treated participants categorized by sex (male or female) and by race (Black or White).
Detailed methods for the two phase 3 studies (NCT03168334 and NCT03168321) have been reported.6 In brief, both were multicenter, double-blind, randomized, vehicle-controlled, parallel group phase 3 studies. Key eligibility criteria included: male or female, age 9 years or older; moderate or severe acne (Evaluator's Global Severity Score [EGSS] of 3 or 4); 20–50 facial inflammatory lesions (papules, pustules, and nodules); 25–100 noninflammatory lesions (open and closed comedones); and ≤2 facial nodules. Eligible patients were randomized 1:1 to receive tazarotene 0.045% lotion or vehicle, applied oncedaily to the face 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. The study protocol was approved by institutional review boards or ethics committees at all investigational sites. Studies were carried out in accordance with principles of Good Clinical Practice (GCP) and the Declaration of Helsinki. All patients or their legal guardians provided written informed consent.
Quality of Life Assessment
Quality of life was assessed using the Acne-QoL, which includes 19 items in 4 different domains: self-perception (items 1, 2, 3, 6, and 10); role-emotional (items 4, 5, 7, 8, and 9), role-social (items 11, 12, 13, and 14), acne symptoms (items 15, 16, 17, 18, and 19). For each item, participants were asked to rate the degree to which acne has affected them with a score of 0 (“extremely”) to 6 (“not at all”). Higher scores indicated better quality of life, and a positive score change indicated improvement.
Post Hoc Analyses
All analyses were based on the pooled intent-to-treat (ITT) population, defined as randomized participants who were provided with study drug. Mean changes from baseline to week 12 in Acne- QoL domain and item scores were analyzed in the pooled ITT population using an analysis of covariance (ANCOVA) with treatment group as a factor and baseline score as a covariate; P<0.05 indicated statistical significance between tazarotene 0.045% lotion and vehicle lotion. The ANCOVA model was also used to investigate Acne-QoL outcomes in participants categorized by EGSS score at baseline (score of 3 [moderate acne symptoms] or 4 [severe acne symptoms]) and by median Acne-QoL total score at baseline in the pooled ITT population (score ≥60 [better quality of life] or <60 [worse quality of life]).
Because differences in sex and race had been observed between the EGSS subgroups and between the Acne-QoL subgroups, exploratory analyses were conducted in demographic subgroups. Mean changes from baseline to week 12 in Acne-QoL domain scores were analyzed descriptively in tazarotene-treated participants categorized by sex (male or female) and by race (Black or White).
RESULTS
Participants
In the pooled ITT population (N=1614), mean Acne-QoL domain scores at baseline were similar between participants who received tazarotene 0.045% and those who received vehicle lotion (Table 1). Relative to the subgroup with moderate acne symptoms at baseline (EGSS score=3; n=1467), the subgroup with severe acne symptoms (EGSS score=4; n=147) had fewer female participants (52.4% vs 67.3%) and Black participants (8.2% vs 17.0%). This trend was reversed in Acne-QoL subgroups. Relative to the subgroup with better patient-reported quality of life at baseline (total score ≥60; n=819), the subgroup with worse quality of life (total score <60; n=791) had more female participants (80.5% vs 52.0%) and Black participants (19.1% vs 13.4%). Mean age was comparable between EGSS subgroups (20.5 vs 19.8 years [score=3 vs score=4]) and between Acne-QoL subgroups (22.5 vs 18.6 years [score <60 vs score ≥60]).
Quality of Life Improvements
In the pooled ITT population, mean improvements from baseline to week 12 in Acne-QoL scores (domains and items) were generally greater in participants treated with tazarotene 0.045% lotion than in those who received vehicle lotion (Figure 1). Significant differences between tazarotene 0.045% lotion and vehicle lotion (P<0.05) were found as follows: the acne symptoms domain; 3 items within the acne symptom domain (bumps on face, bumps full of pus, concerned with scarring); 2 items within the self-perception domain (feel embarrassed, dissatisfied with appearance); 1 item within the role-emotional domain (feel upset), and 1 item within the role-social domain (interacting with opposite sex or same sex if applicable).
In the EGSS subgroups, the magnitude of Acne-QoL improvements with tazarotene 0.045% lotion was generally comparable between participants with moderate symptoms at baseline (score=3) and those with severe symptoms (score=4; Figure 2). In the EGSS score=3 subgroup, statistical significance for tazarotene 0.045% lotion was found in the acne symptoms domain and in 3 acne symptoms items (bumps on face, bumps full of pus, concerned with scarring; P<0.05 versus vehicle lotion;
In the pooled ITT population (N=1614), mean Acne-QoL domain scores at baseline were similar between participants who received tazarotene 0.045% and those who received vehicle lotion (Table 1). Relative to the subgroup with moderate acne symptoms at baseline (EGSS score=3; n=1467), the subgroup with severe acne symptoms (EGSS score=4; n=147) had fewer female participants (52.4% vs 67.3%) and Black participants (8.2% vs 17.0%). This trend was reversed in Acne-QoL subgroups. Relative to the subgroup with better patient-reported quality of life at baseline (total score ≥60; n=819), the subgroup with worse quality of life (total score <60; n=791) had more female participants (80.5% vs 52.0%) and Black participants (19.1% vs 13.4%). Mean age was comparable between EGSS subgroups (20.5 vs 19.8 years [score=3 vs score=4]) and between Acne-QoL subgroups (22.5 vs 18.6 years [score <60 vs score ≥60]).
Quality of Life Improvements
In the pooled ITT population, mean improvements from baseline to week 12 in Acne-QoL scores (domains and items) were generally greater in participants treated with tazarotene 0.045% lotion than in those who received vehicle lotion (Figure 1). Significant differences between tazarotene 0.045% lotion and vehicle lotion (P<0.05) were found as follows: the acne symptoms domain; 3 items within the acne symptom domain (bumps on face, bumps full of pus, concerned with scarring); 2 items within the self-perception domain (feel embarrassed, dissatisfied with appearance); 1 item within the role-emotional domain (feel upset), and 1 item within the role-social domain (interacting with opposite sex or same sex if applicable).
In the EGSS subgroups, the magnitude of Acne-QoL improvements with tazarotene 0.045% lotion was generally comparable between participants with moderate symptoms at baseline (score=3) and those with severe symptoms (score=4; Figure 2). In the EGSS score=3 subgroup, statistical significance for tazarotene 0.045% lotion was found in the acne symptoms domain and in 3 acne symptoms items (bumps on face, bumps full of pus, concerned with scarring; P<0.05 versus vehicle lotion;
