Treatment of Periorbital Facial Wrinkles in Female Subjects: A Randomized, Multi-Center, Double-Blinded, Placebo-Controlled, Split-Face Study Evaluating Procedure Pairing of a Peptide Anti-Aging Serum with Onabotulinumtoxina

Dear Editor:

There is a growing demand for treatments for mimetic wrinkles within dermatology and plastic surgery clinics beyond neuromodulator injections.1 In 2002, the United States (US) Food and Drug Administration (FDA) approved onabotulinumtoxinA (Botox^®; Allergan, Dublin, Ireland) as an effective temporary treatment in reducing the appearance of moderate-to-severe mimetic wrinkles.1,2 While onabotulinumtoxinA softens mimetic wrinkles, the overall skin appearance, texture, firmness, and roughness are not directly targeted. Thus, there is a critical need for safe postprocedure pairing cosmeceuticals that can work synergistically with neuromodulators to improve the appearance of facial expression lines as well as enhance overall skin health. A skincare regimen combining in-office procedures with at-home care would enhance patient offerings.

A mimetic line targeted peptide-based treatment serum (LTPS) combining five neuromodulating peptides and gamma aminobutyric acid (GABA) clinically improved the appearance of expression lines in women with mild-to-moderate fine lines and wrinkles after twice-daily application for twelve weeks in a stand-alone study.3 It was hypothesized that this LTPS would provide synergistic effects in pairing with neuromodulators, as well as overall skin health with statistical significance when compared to a placebo serum (PS) paired with a neuromodulator in women with moderate-to-severe crow’s feet wrinkles and fine lines.

In a multicenter, randomized, split-faced, double-blinded, placebo-controlled study with two board certified dermatologists and an aesthetic physician, 36 female subjects between the ages of 35 to 60 with Fitzpatrick Skin Types I to VI, moderate-to-severe crow’s feet wrinkles, and fine lines, who were not pregnant nor planning to become pregnant during the duration of the study nor had been diagnosed with an autoimmune disease, were enrolled. Blinded subjects were randomized to receive the LTPS and PS using a randomization table prepared prior to the start of the study by a non-participating staff member. Subjects were assigned a subject number in numerical order as enrolled and were provided a set of products labeled “R” right and “L” left (depending on the randomization of that subject). Subjects received 10 to 12 units of onabotulinumtoxinA injection (following FDA-approved criteria) in the crow’s feet area bilaterally to have the subject act as their own control. The dosing the subjects received needed to be at a level that would be considered full treatment to demonstrate efficacy thereby raising the difficulty of demonstrating a statistically significant effect. Subjects applied products immediately following neuromodulator injection and twice daily for 12 weeks to the right and left periorbital and lateral canthal region, along with a provided bland moisturizer and sunscreen. Blinded clinical grading was performed using the Modified Griffith’s 10-point scale.4

Twenty-nine female subjects with an average age of 49.7 (range 37 to 59 years), across three study centers completed the study. Female subjects were predominantly White (90%), followed by Hispanic (10%), and had primarily Fitzpatrick Skin Type III (59%), followed by Fitzpatrick Skin Type II (21%), Type I (14%), and Type IV (7%). Two sites injected 12 units of onabotulinumtoxinA and one site injected 10 units of onabotulinumtoxinA on both canthal sides across their patients at baseline. LTPS demonstrated superior efficacy by statistically significantly outperforming the PS in improving under-eye fine lines and wrinkles at rest, 26.63 percent (**p<0.01) and 19.60 percent (*p<0.05) respectively, at Week 12 compared to baseline. Similarly, LPTS showed superiority to PS by statistically significantly improving under eye fine lines, 26.12 per (**p<0.01), and periorbital skin texture, 30.82% (*p<0.05), at max smile at Week 12 compared to baseline (Figure 1). Improvement in clinical efficacy parameters, including undereye fine lines and wrinkles and periorbital skin texture, were further demonstrated by VISIA^® in standard light; under-eye fine lines and wrinkles at rest (Figure 2A, B, C, D) and at max smile (Figure 2E, F). 3D PRIMOSCR imaging was not performed in this study, however in the stand-alone study PRIMOSCR results indicated an improvement in wrinkle length and total wrinkle count.3

FIGURE 1.

Clinical efficacy parameters assessed by clinical investigators across three sites using the modified Griffith’s 10-point scale; percent mean change from baseline between LTPS/onabotulinumtoxinA and placebo serum/onabotulinumtoxinA at Week 12.

FIGURE 2.

(A, B, C, D) VISIA^® clinical photography of subject’s face at rest. Female subject was 43 years old, Fitzpatrick skin type III; (A, C) baseline and (B, D) week 12. (E, F) VISIA^® clinical photography at maximum smile. Female subject was 52 years old, Fitzpatrick skin type II Right side treated with LTPS + Botox^® and left side treated with placebo serum + Botox^®.

The results of the novel topical LTPS with five neuromodulating peptides and GABA are attributed to blunting of the concentration of acetylcholine at the epidermal surface, thus mitigating horizontal and vertical expression lines.5 Providing a synergistic skincare solution that combines the benefits of in-office neuromodulator procedures and an at-home skincare regimen to enhance patient offerings, improve facial expression lines, and long-term skin health.