A Double-Blind, Randomized Clinical Trial to Determine Effects of Increasing Doses and Dose-Response Relationship of IncobotulinumtoxinA in the Treatment of Glabellar Rhytids

Abstract

Abstract Background IncobotulinumtoxinA is an effective neuromodulator for treating glabellar rhytids. The relationship between dose and reduction in rhytid severity is well established. However, the effects of escalating doses on the treatment duration response are less understood. Objectives The aim of this study was to assess the effects of increasing doses of incobotulinumtoxinA on the treatment duration for glabellar rhytids. Methods A randomized, double-blind, Phase IV study was conducted at a fully accredited, outpatient surgical facility. Subjects (31 female, 7 male) with moderate to severe glabellar rhytids were randomized to 1 of 3 incobotulinumtoxinA dose groups: 20, 60, or 100 U. Effect duration was determined by calculating the time to return to baseline for dynamic glabellar lines during maximal contraction. Follow-up was completed through 1 year, and adverse events were monitored. Results The median duration of effect was 120 days (95% confidence interval [CI] [90, 180 days]), 180 days (95% CI [180, 210 days]), and 270 days (95% CI [240, 330 days]) for the 20-, 60-, and 100-U groups, respectively. A Wald chi-square test from the Cox regression on the primary efficacy variable indicated a statistically significant effect of dose group on time to baseline (chi square = 54.63; df = 2; P < 0.001). Hazard ratios were HR = 0.21 (95% CI [0.10; 0.43] for the 60-U vs the 20-U group, and HR = 0.06 (95% CI [0.10; 0.43]) for the 100-U vs the 20-U group, indicating a statistically longer return to baseline for both the 60- and 100-U cohorts. Conclusions There is a dose-dependent relationship between incobotulinumtoxinA and duration of effect in the glabella. Level of Evidence: 2