OnabotulinumtoxinA (Botox) in the Treatment of Crow's Feet Lines in Japanese Subjects

Abstract

Background: This study evaluated the safety and efficacy of onabotulinumtoxinA in Japanese subjects with crow's feet lines (CFL).

Methods: This phase 3, multicenter, double-blind, randomized study included 2 treatment periods: 6-month placebo-controlled period followed by a 7-month open-label period. In period 1, subjects with moderate to severe CFL received onabotulinumtoxinA 24 U (n = 104) or 12 U (n = 99), or placebo (n = 97). In period 2, placebo subjects switched to onabotulinumtoxinA 24 U or 12 U (double-blind dose). Up to 5 total treatments were permitted for subjects meeting re-treatment criteria. The primary efficacy measure was the proportion of investigator-assessed responders (achieving CFL severity of none or mild at maximum smile using the Facial Wrinkle Scale with Asian Photonumeric Guide [FWS-A] at day 30 of treatment 1). Additional endpoints included other responders (achieving at least 1-grade improvement at maximum smile and at rest using the FWS-A at day 30), responders at other time points, duration of effect, subject-reported outcomes, and safety.

Results: All efficacy endpoints were met. At day 30, the proportion of subjects achieving none or mild severity at maximum smile was significantly greater (P < 0.001) in the onabotulinumtoxinA 24 and 12 U groups (68.3 and 56.6%, respectively) compared with the placebo group (8.2%). Efficacy results were consistent over repeated treatments, and subjects' self-assessed outcomes were similar to investigator-assessed results.

Conclusions: Treatment with onabotulinumtoxinA 24 and 12 U improved the appearance of CFL in Japanese subjects and was well tolerated, with no new safety findings.

Level of evidence i: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Keywords: Botox; Botulinum toxins, type A; Neurotoxins; Skin aging.

Conflict of interest statement

K. Harii, M. Kawashima, and N. Furuyama have no conflicts to disclose. X. Lei, R. Hopfinger, and E. Lee are employees and stockholders of Allergan plc.

Figures

Fig. 1

Alternative injection patterns for treatment of crow’s feet lines. a The first injection was in the orbicularis oculi at the level of the lateral canthus, at least 1.5–2.0 cm temporal to the lateral canthus and just temporal to the lateral orbital rim (marked as AX). The second injection was 1.0–1.5 cm above this first injection site, at an approximately 30° angle medially (marked as BX). The third injection was 1.0–1.5 cm below the first injection site, at an approximately 30° angle medially (marked as CX). b If the lines in the crow’s feet region were primarily below the lateral canthus, the injector had the option to inject below the lateral canthus. Injections were given in a line angling from anteroinferior to superoposterior, with the most anterior injection point lateral to a line drawn vertically from the lateral canthus and the most inferior injection superior to the maxillary prominence. Reprinted with permission from Carruthers et al. [2]

Fig. 2

Subject disposition. a Randomized treatment assignment in Period 1. b Randomized treatment assignment in Period 2. c Received placebo

Fig. 3

Proportion of subjects achieving none or mild severity of crow’s feet lines at maximum smile, through day 90 of first treatment (intent-to-treat population). P < 0.001 at every time point for both onabotulinumtoxinA 24 U & 12 U versus placebo

Fig. 4

Proportion of subjects achieving none or mild severity of crow’s feet lines at maximum smile, through day 90 of each treatment using the FWS-A (intent-to-treat population). FWS-A, Facial Wrinkle Scale with Asian Photonumeric Guide

Fig. 5

Proportion of subjects achieving at least a 1-grade improvement in severity of crow’s feet lines at maximum smile (a) and at rest (b), through day 90 of each treatment using the FWS-A (intent-to-treat population). FWS-A, Facial Wrinkle Scale with Asian Photonumeric Guide

Fig. 6

Representative photographs of Subject 1 and Subject 2 taken at baseline (A, C) and at the end of treatment period 1 on day 30 (B, D). Subject 1, a 53-year-old Japanese female, received onabotulinumtoxinA 12 U, while Subject 2, a 55-year-old Japanese female, received onabotulinumtoxinA 24 U