Safety, Tolerability, and Efficacy of Repeat-Dose Injections of IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results from a Prospective, Open-Label, Phase III Study

May 2020 | Volume 19 | Issue 5 | Original Article | 461 | Copyright © May 2020

Published online April 24, 2020

Tanja Fischer , Gerhard Sattler , Welf Prager , Berthold Rzany , Tatjana Pavicic , Gerd Gauglitz , Petra Weissenberger , Shahbaz Riaz

aHaut- and Lasercentrum, Potsdam, Germany bRosenparkklinik GmbH, Darmstadt, Germany cPrager and Partner Dermatologische Praxis, Hamburg, Germany dRZANY & HUND Privatpraxis, Berlin, Germany eDermatologische Praxis, Munich, Germany fLudwig-Maximilian University, Munich, Germany gMerz Pharmaceuticals GmbH, Frankfurt, Germany hFormerly Merz North America, Raleigh, NC iUniversity of Hamburg, Hamburg, Germany

Abstract
In aesthetic practice, wrinkles in the upper face are commonly treated with repeat-dose injections. The objective of this study was to investigate the safety, tolerability, and efficacy of repeat-dose injections of incobotulinumtoxinA in the combined treatment of moder-ate to severe upper facial lines (UFL) [glabellar frown lines (GFL), horizontal forehead lines (HFL), and lateral periorbital lines (LPL)]. Healthy subjects (≥18 years) with moderate to severe GFL, HFL, and LPL on the Merz Aesthetics Scales (MAS) at maximum contrac-tion were administered 54 to 64 U of incobotulinumtoxinA (GFL, 20 U; HFL, 10 to 20 U; LPL, 24 U) in up to four, 120-day treatment cycles. Adverse events (AE) were recorded for each cycle until 120 ± 7 days after treatment. Investigator-assessed MAS scores were evaluated for each treated area at maximum contraction on day 30 [responder = score of “none” (0) or “mild” (1)]. Subject-assessed scores for overall appearance of the upper face of “much improved” or “very much improved” were noted at day 30 of each treatment cycle on the Global Impression of Change Scale (GICS). Overall, 140 subjects were treated, and 125 subjects completed the study. Mean injected units per injection cycle ranged from 56.3 U to 57.7 U. During the four-cycle study period 17.1% of total treated subjects experienced a treatment emergent adverse event (TEAE). TEAEs of special interest were documented for 9 subjects (6.4%), in 6 of these subjects (4.3%) the TEAEs were related to treatment. No clinically significant mean changes in laboratory and vital-sign values were observed from screening to final-treatment visit. Over the study interval, a response rate of > 80% on the investigator-assessed MAS was reported for all treated areas except HFL. Greater than 80% of subjects in cycles 1, 3, and 4 and 78.5% of subjects in cycle 2 reported ratings of “much improved” or “very much improved” on the GICS for the overall appearance of the upper face. Incobotu-linumtoxinA for the repeat-dose treatment of UFL is safe and well tolerated with a stable safety profile, without new formation of neutralizing antibodies and has excellent efficacy during prolonged administration.

J Drugs Dermatol. 2020;19(5):461-469. doi:10.36849/JDD.2020.5013

INTRODUCTION

IncobotulinumtoxinA (Xeomin/Xeomeen/Bocouture/XEOMIN Cosmetic; botulinum toxin type A free from complexing proteins [150 kDa]; Merz Pharmaceuticals GmbH) is indicated worldwide for the correction of glabellar frown lines (GFL) and in Europe additionally for lateral periorbital lines (LPL; crow’s feet) and upper facial lines (UFL; ie, simultaneous treatment of GFL, LPL, and horizontal forehead lines [HFL]).1 The efficacy of incobotulinumtoxinA in the treatment of multiple or singular facial areas has been extensively demonstrated.2-10 With the recent surge in interest for a more holistic approach, consisting of combined treatment of GFL, HFL, and LPL in a single treatment session, there is a need for demonstrating safety and efficacy for such procedures.9-14 In 2015, the first-placebo-controlled, randomized, double-blind study provided clinically significant evidence for the efficacy and safety of incobotulinumtoxinA (54 to 64 U) for the combined treatment of moderate to severe GFL, HFL, and LPL (P<0.001 for all 3 areas).9 Treatment response was defined as investigator-assessed scores of “0” (none) or “1” (mild) on the 5-point Merz Aesthetics Scales (MAS) at maximum contraction on day 30 for GFL, HFL, and LPL.