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A Double-Blind, Comparative Clinical Study of Newly Formulated Retinol Serums vs Tretinoin Cream in Escalating Doses: A Method for Rapid Retinization With Minimized Irritation

June 2020 | Volume 19 | Issue 6 | Original Article | 625 | Copyright © June 2020


Published online May 8, 2020

Zoe Diana Draelos , R. Scott Peterson

aDermatology Consulting Services PLLC bTOPIX Pharmaceuticals, Inc.

Abstract
Objective: The goal of this 12 week, double-blinded, controlled, clinical study was to compare the efficacy, tolerability, and consumer acceptance of three novel retinol serums to tretinoin.
Method: Forty-five photoaged females ages 35-65, Fitzpatrick skin types I-IV, with moderate wrinkling were enrolled in the 12-week study. A step-up protocol for increasing the dose of retinol serum (0.25%, 0.5%, 1.0%) or tretinoin cream (0.025%, 0.05%, and 0.1%) in combination with a test moisturizer or currently marketed dermatologist-recommended moisturizing cream was used. Overall severity of investigator graded photodamage, subject assessed photodamage, and tolerability criteria were evaluated using a 5-point ordinal scale at weeks 4, 8, and 12. Facial photography occurred at each visit and TEWL was measured at baseline and week 12. Histologic evaluation of punch biopsies was completed on baseline and week 12 samples.
Results: After 12 weeks of use, both retinol serum and tretinoin demonstrated parity across investigator and subject assessment measurements as well as diagnostic measures including TEWL. Retinol serum subjects showed significant week 4 improvement in visual skin smoothness compared to tretinoin subjects (P=0.031). There was highly significant improvement in skin dryness with the retinol serum (P<0.001) not seen in the tretinoin group. Histologic analysis of baseline and 12-week punch biopsies demonstrated newly formed collagen and greater epidermal thickening in retinol serum subjects compared to tretinoin treated subjects.
Conclusion: Retinol serum (0.25%, 0.5%, 1.0%) was safe and effective with equivalent/or better performance and tolerability than tretinoin creams.

J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.5085

INTRODUCTION

Photoaging is the result of ultraviolet (UV)-induced damage to exposed skin. Superimposed upon intrinsic aging, photoaging accounts for most age-related changes in the appearance of skin. As skin ages, it becomes thinner, drier, and less elastic due to slowing of regenerative processes.1

Youthful skin is characterized by its unblemished, evenly pigmented, smooth, pink appearance. This contrasts with intrinsically aged skin, which is thin, inelastic, and finely wrinkled with deepening of facial expression lines. These changes are evident histologically as a thinned epidermis and dermis with flattening of the rete pegs at the dermal epidermal junction. Extrinsically aged, sun-exposed skin appears clinically as blemished, thickened, yellowed, lax, rough, and leathery. These changes may begin as early as the second or third decade and accelerate beyond.

The best-studied ingredient category for anti-aging benefits is retinoids, investigated for their ability to reduce manifestations of photodamage such as wrinkles, hyperpigmentation, and skin laxity.2,3,4 Retinoids, especially retinoic acid, have been shown to decrease melanin, increase deposition of collagen in the papillary dermis and improve the morphology of elastic fibers.5,6,7 Retinoids include retinol (vitamin A) and its natural derivatives such as retinaldehyde, retinyl esters, and tretinoin (retinoic acid). The most extensively studied retinoid is retinoic acid.8,9,10 Tretinoin is a prescription retinoic acid commonly used as treatment for photoaged skin; however, it is associated with poor tolerability.11 It is well-documented that retinol produces less skin erythema and scaling than retinoic acid. Gold and colleagues wrote that burning, pruritus, dryness, and erythema were “minimal” with a topical formulation of 0.5% retinol.12,13

Although retinol appears to be a viable candidate for the treatment of photoaged skin, retinol is easily degraded to biologically inactive forms when exposed to light and air.14,15,16 For this reason, the efficacy of retinol in the treatment of photodamage depends greatly on its mode of delivery to the target area and formulation.