Novel Tretinoin 0.05% Lotion for the Once-daily Treatment of Moderate-to-Severe Acne Vulgaris in an Adult and Adolescent Female Population

February 2019 | Volume 18 | Issue 2 | Original Article | 178 | Copyright © February 2019

Leon H. Kircik MD,1 Hilary Baldwin MD,2,3 Edward Lain MD MBA,4 Eric Guenin PharmD PhD,5 Susan Harris MS,6 Varsha Bhatt PhD7

1Indiana University School of Medicine, Indianapolis, IN, Physicians Skin Care, PLLC, Louisville, KY, Icahn School of Medicine at Mount Sinai, New York, NY 2The Acne Treatment and Research Center, Morristown, NJ 3Rutgers Robert Wood Johnson Medical Center, Newark, NJ 4Austin Institute for Clinical Research, Austin, TX 5Ortho Dermatologics, Bridgewater, NJ 6Bausch Health, Bridgewater, NJ 7Dow Pharmaceutical Sciences Inc., Petaluma, CA

Abstract
BACKGROUND: Acne vulgaris (acne) is a common dermatological condition typically associated with adolescents, affecting about 85% of young people. However, it is also prevalent and persistent into adulthood, particularly in females. The efficacy of tretinoin in acne is well documented with large pivotal studies. The first lotion formulation of tretinoin was developed to provide an important alternative option to treat acne patients who may be sensitive to the irritant effects of other tretinoin formulations.OBJECTIVE: To determine whether efficacy and safety of tretinoin 0.05% lotion was similar in adolescent (less than 18 years) and adult (less than equal to18 years) women with moderate-to-severe acne.METHODS: Post hoc analysis of two multicenter, randomized, double-blind, vehicle-controlled Phase 3 studies in moderate or severe acne. Female subjects (aged 9 to 58 years, N=909) randomized (1:1) to receive tretinoin 0.05% lotion or vehicle, once-daily for 12 weeks. Efficacy assessments included changes in baseline inflammatory and noninflammatory lesions and treatment success (at least 2-grade reduction in Evaluator’s Global Severity Score [EGSS] and clear/almost clear). Safety, adverse events (AEs), and cutaneous tolerability were evaluated throughout.RESULTS: At week 12, mean percent reduction in inflammatory and noninflammatory lesion counts in female subjects were 56.9% and 51.7%, respectively, compared with 47.1% and 34.9% with vehicle (P equals less than 0.001). Similar results were seen in adult and adolescent females in terms of reduction in inflammatory lesion counts with tretinoin 0.05% lotion; reduction in noninflammatory lesions was significantly greater in adult females (P equals 0.002). Treatment success was achieved by 23.6% of female subjects by week 12, compared with 13.5% on vehicle (P less than 0.001). Although treatment success was somewhat greater in adult females (24.6% versus 21.6%), the difference was not significant. The majority of AEs were mild and transient. There were five serious AEs (SAEs) reported (4/1, adult/adolescent, respectively). The most frequently reported treatment related AEs with tretinoin 0.05% lotion were application site pain (3.0%/5.7%), and application site dryness (4.9%/6.4%). Local cutaneous safety and tolerability assessments were generally mild-to-moderate and improved by week 12. Slight increases in mean scores were observed for scaling, burning and stinging within the first four weeks and appeared to be transient.CONCLUSIONS: Tretinoin 0.05% lotion was significantly more effective than its vehicle in achieving treatment success and reducing inflammatory and noninflammatory lesions in female acne. Noninflammatory lesion count reduction was significantly greater in adult females compared with adolescent females. The new lotion formulation was well-tolerated.J Drugs Dermatol. 2019;18(2):178-188.

INTRODUCTION

Although acne vulgaris (acne) is principally a disorder of adolescence, research suggests the prevalence of adult acne is increasing, especially in females.1,2 The most common type of acne seen in adult females (in about 80% of cases) is persistent acne, which continues from adolescence into adulthood.1,3 While most adult women with acne will have both inflammatory and noninflammatory lesions, those with persistent acne tend to have a higher proportion of comedones than those with the late-onset acne (which typically first presents between the ages of 21 to 25 years).4Important considerations when selecting a treatment for adult female acne are the slower response to treatment, increased likelihood of skin irritation, and greater psychosocial impact of the disease.5 Consequently, formulations which are less irritating may be beneficial.6 Topical retinoids are highly effective in