Efficacy and Tolerability of a Double-Conjugated Retinoid and Alpha Hydroxy Acid Cream in Subjects With Mild to Moderate Blemish-Prone Skin

January 2022 | Volume 21 | Issue 1 | 54 | Copyright © January 2022

Published online December 24, 2021

Deanne M. Robinson MD FAADa, Daniel P. Friedmann MD FAADb, Jennifer Gordon MDb, Mitchell Wortzman PhDc, Diane B. Nelson RN MPHc

aModern Dermatology, Westport, CT
bWestlake Dermatology Clinical Research Center, Westlake Dermatology & Cosmetic Surgery, Austin, TX
cSkinbetter Science, LLC, Phoenix, AZ

Background: Topical retinoids influence the rate of cellular turnover and improve skin clarity and photoaged skin. Consequent cutaneous irritation reduces adherence resulting in suboptimal outcomes. A formulation comprised of a double-conjugated molecule containing a retinoid and an alpha hydroxy acid (AHA) has been purposefully developed for individuals with blemish-prone skin.
Design and Methods: A 12-week study conducted in subjects with mild/moderate blemish-prone skin evaluated skin clarity utilizing the Investigators Global Assessment Scale (0-Clear to 4-Severe). Changes in the appearance of pores were evaluated using a 6-point scale (0-None to 5-Severe). Adverse Events (AEs) and subject satisfaction were captured. A secondary analysis evaluated visible, quantitative changes in pores.
Results: Twenty subjects enrolled; 19 subjects completed the study. Mean percent improvements in appearance from baseline in skin clarity were demonstrated at weeks 4 (43%; P<.0001), 8 (48%; P<.0001) and 12 (50%; P<.0001). Mean percent visible improvements from baseline in pores were observed at 4, 8, and 12 weeks (33% [P<.0001]; 21% [P=.04] and 25% [P=.0006], respectively). AEs were mild and transient. By 8 weeks, all subjects reported improvement in overall appearance and that their skin was healthier looking. Secondary quantitative analysis (n=6) demonstrated an 18% mean improvement in the appearance of pores from baseline at week 12.
Conclusions: A double-conjugated retinoid/AHA cream specifically developed for individuals with blemish-prone skin demonstrated early improvements in the appearance of skin clarity and pores over 12 weeks. AEs were mild and transient. Subjects reported high levels of satisfaction in the overall appearance and quality of skin.

J Drugs Dermatol. 2022;21(1):54-59. doi:10.36849/JDD.6415


Acne is a common dermatologic condition that predominantly affects teenagers. However, acne often persists or may first appear in adulthood, and can substantially impact self-esteem, quality of life and productivity (work or school).1,2 Primarily owing to hormonal imbalances, at least 50% of women 20-29 years of age and more than 35% of women aged 30-39 years of age experience acne,2-9 which is more likely to be mild to moderate in severity.3,5,8,10-12 Management of mild to moderate acne typically involves topical therapies.

Common topical treatments include benzoyl peroxide, Vitamin A derivatives or retinoids, alpha hydroxy acids (AHAs, such as lactic and glycolic acids), beta hydroxy acids (BHAs, such as salicylic acid), azelaic acid, and antibiotics, used alone or in varying combinations.7,9,13,14 Each treatment has unique mechanisms of action, benefits and limitations, and may be available in prescription or non-prescription (i.e., over the counter [OTC] or cosmetic) strengths. A wide variety of cosmetic products exist in the market today, not to treat acne per se, but to provide clearing and clarifying effects for consumers who may not wish to seek pharmaceutical or medical intervention for acne as a dermatological condition. Retinoids are a foundational component of topical treatments for adults owing to their comedolytic activity and benefits for photodamaged or aging skin. Retinoids increase cellular mitosis, stimulate collagen production, normalize melanocyte function, and regulate skin cell metabolism resulting in improvements in lines and wrinkles, skin tone, skin texture, skin clarity and overall improvement in the quality of skin.7-9,15-22 Unfortunately, cutaneous irritation often accompanies use leading to reduced adherence and suboptimal outcomes.8,21,23

Highly keratolytic, salicylic acid is an ideal ingredient for acne-prone skin as it is an oil-soluble molecule that readily penetrates pores, dissolving oil and debris, reducing and