A Randomized, Double-blind, Split-face Study Comparing the Efficacy and Tolerability of Three Retinol-based Products vs. Three Tretinoin-based Products in Subjects With Moderate to Severe Facial Photodamage
January 2015 | Volume 14 | Issue 1 | Original Article | 24 | Copyright © January 2015
Published online January 1, 2015
Michael Babcock MD,1 Rahul C. Mehta PhD,2 Elizabeth T. Makino BS CCRA MBA2
1Thomas J. Stephens & Associates, Carrollton, TX
2SkinMedica, an Allergan Company, Carlsbad, CA
Abstract
Retinol, has been shown to improve the appearance of photodamaged skin when applied topically, and is generally considered to be approximately ten times less potent than tretinoin. To assess this theory, three cosmetic formulations containing 0.25%, 0.5%, and 1.0% retinol were developed to correspond to the three commonly prescribed concentrations of tretinoin (0.025%, 0.05%, and 0.1%). A randomized, double-blind, split-face comparison study was conducted to compare the three concentrations retinol (Ret) including 0.25%, 0.5%, and 1.0%, against the respective three strengths of tretinoin (Tret) 0.025%, 0.05%, and 0.1% in subjects with moderate to severe facial photodamage. Subjects were randomized into three groups: Group 1 (Ret 0.25% vs. Tret 0.025%); Group 2 (Ret 0.5% vs. Tret 0.05%); and Group 3 (Ret 1.0% vs. Tret 0.1%). Within each group, subjects were randomized to apply Ret on one half of the face (left or right) and Tret on the other facial side, for a duration of twelve weeks. Clinical evaluations for efficacy and tolerability, as well as standardized digital photographs were conducted at baseline and at weeks 4, 8, and 12. Sixty-five subjects completed the twelve-week study (Group 1: n=24, Group 2: n=20, and Group 3: n=21). At week 12 in all treatment groups, both Ret and Tret produced statistically significant improvements from baseline in all efficacy parameters, including overall photodamage, fine lines/wrinkles, coarse lines/wrinkles, skin tone brightness, mottled pigmentation, and tactile roughness (all
P<0.001). There were no significant differences in efficacy between Ret and Tret in these efficacy parameters. Results from this comparison study suggest that this sustained-release retinol complex containing multiple agents for optimal irritation control provides comparable improvements to tretinoin in the appearance of photodamage.
J Drugs Dermatol. 2015;14(1):24-30.
BACKGROUND
Retinoic Acid (tretinoin)
Topically applied retinoic acid (RA), or tretinoin, has been
formally established as an effective treatment for photodamaged
skin. With over thirty years of research data to
support its clinical and histological effects, tretinoin is also the
most extensively studied therapy for photodamage.1-12 Clinical
signs of photodamage include the presence of fine and coarse
wrinkles, mottled pigmentation, uneven skin tone, and rough
skin texture. These characteristics also manifest in intrinsically
or chronologically-aged skin and have also been shown to respond
to treatment with tretinoin.14-16 Numerous clinical studies
with tretinoin have shown significant improvements in these
parameters, along with supporting histological evidence of increased
epidermal thickness, stratum corneum compaction,
decreased melanin content, as well as an increased deposition
and organization of collagen and elastin fibers.8, 9, 12, 13 Tretinoin
achieves these effects by binding nuclear retinoic acid receptors,
and inducing a variety of molecular changes in the skin including
keratolytic activity, inhibition of matrix metalloproteinase production,
and stimulation of collagen synthesis.17-19 Currently, topical
tretinoin is available in concentrations ranging from 0.02% to
0.1%, with the most frequently recommended products available
in the following concentrations: 0.025%, 0.05%, and 0.1%.20
Retinol is a cosmetic ingredient and is one of the most active vitamin
A derivatives, that is a metabolic precursor of RA. Topically
applied retinol has been shown to improve the appearance of
photodamaged skin.21, 22 The bioactivity of retinol in the skin relates
to its conversion to RA, the “active†form, which then exerts
a variety of effects discussed above. A simplified overview of RA’s
metabolic precursors converting to RA is provided in Figure 1.
Cosmetic products are generally perceived as less effective or
unable to produce the clinical improvements in photodamaged
skin achieved with prescription products such as RA. Taking into
account that retinol is a metabolic precursor to RA, an established
treatment for photodamaged skin, it follows that retinol
may have a greater potential to achieve similar clinical effects.
