Tretinoin 0.05% Lotion for the Once-Daily Treatment of Moderate and Severe Acne Vulgaris in Females: Effect of Age on Efficacy and Tolerability

BACKGROUND: While it is generally considered to be a disease of adolescence, acne affects an increasing number of adults, especially women. Although data exist on the use of retinoids in adult females, there is no universal agreement as to the age of onset of adult female acne, or data on the efficacy and tolerability dependent on age. A novel tretinoin 0.05% lotion formulation has been shown to be effective and well-tolerated in acne patients with moderate or severe disease. OBJECTIVE: To evaluate the safety and efficacy of once-daily tretinoin 0.05% lotion in women with moderate or severe acne categorized into different age groups (13-19, 20-29, and 30+ years). METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies. Women (aged 13-19 years, N=357; 20-29 years, N=352; 30+ years, N=156) with moderate or severe acne were randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory/noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator's Global Severity Score [EGSS] and 'clear'/'almost clear') and Quality of Life (QoL) using the validated Acne-QoL questionnaire. Safety and adverse events (AEs) where evaluated throughout; cutaneous tolerability assessed at each study visit using a 4-point scale (where 0=none and 3=severe). RESULTS: At baseline, 91.9% (N=794) of women in the post hoc analysis had moderate (EGSS=3) and 8.1% (N=70) severe (EGSS=4) acne, with the highest proportion of women (11.1%, N=39) having severe acne being aged 20-29 years. Baseline inflammatory lesion counts were similar across the three age ranges, with more comedonal lesions (44.5) in adolescent females (aged 13-19 years). Quality of life at baseline was much better in adolescent females and may be age-related for some domains (self-perception and role-social). At week 12, there appeared to be an age-related improvement in both inflammatory and noninflammatory lesion counts, and treatment success although the differences between groups were not significant. Mean percent reduction in inflammatory and noninflammatory lesion counts for each age group (13-19, 20-29, and 30+ years old respectively) were 55.3% (P=0.019 versus vehicle), 55.8% (P=0.080) and 63.5%; and 47.1% (P<0.001), 55.2% (P=0.002) and 59.0% (P=0.030). Treatment success for the 3 groups was achieved by 23.2% (P=0.023), 21.3%, and 30.7% of patients, respectively, at week 12; differences between age groups were not significant. Quality of Life improved in all age groups, although changes with tretinoin 0.05% lotion were only significant compared with vehicle in adult females aged 20-29 years (self-perception, role-emotional and acne symptoms); improvements in each domain score by week 12 were also greatest in this age group. The majority of AEs were mild and transient; the most common treatment emergent AEs were application site pain and dryness especially in the older adult females (aged 30+ years). Local cutaneous safety and tolerability assessments were generally mild and improved by week 12. There were transient increases in scaling, burning and stinging in the adolescent females, peaking at week 4; all mean scores were ≤0.6 where 1=mild. CONCLUSIONS: Tretinoin 0.05% lotion was significantly more effective than vehicle in achieving treatment success and reducing inflammatory and comedonal lesions in adult and adolescent females with moderate or severe acne. There appear to be age-related efficacy and tolerability benefits favoring adult females. J Drugs Dermatol. 2019;18(12):1218-1225.