Impact of DaxibotulinumtoxinA for Injection on Brow Position and Frontalis Muscle Activity Following Treatment of Glabellar Lines.

BACKGROUND: Botulinum toxin type A (BoNTA) injections for the treatment of facial lines may lead to pleasant or undesirable changes in eyebrow height and position. OBJECTIVES: The aim of this study was to evaluate the impact of glabellar injection of DaxibotulinumtoxinA for Injection (DAXI), a novel BoNTA formulation, on eyebrow position and frontalis activity. METHODS: This study involved the post hoc analysis of adult patients from the Phase 2a forehead lines (FHL, N = 60) and open-label safety (OLS, N = 175) studies who received a single dose of DAXI 40 U to the glabella and for whom facial photographs were taken at rest and at maximum eyebrow elevation. Median vertical and horizontal displacement of the brows and median forehead strain (an objective quantitative assessment of frontalis activity) from baseline to 2 weeks after glabellar DAXI injection were measured. RESULTS: Two weeks after glabellar DAXI injection, vertical eyebrow movement (at rest) of the lateral brow was observed. In both studies, vertical movement was greatest in the lateral (0.6-0.9 mm) and mid (0.5-0.7 mm) brow regions; movement in the medial brow was negligible (0-0.23 mm). In both studies, a graded reduction in forehead strain was observed 2 weeks post glabellar DAXI injection, with the greatest reduction being in the lower segment (FHL, -73%; OLS, -82%). Treatment with DAXI showed improvements in FHL wrinkle severity. CONCLUSIONS: Glabellar injection of DAXI showed a positive reduction in dynamic frontalis activity that maintained or had a positive effect on eyebrow position. Vertical movement of the brow was suggestive of an improved eyebrow shape with a mild lateral arch.

The Practical Use of AbobotulinumtoxinA in Aesthetics.

Botulinum toxin (BoNT) has been approved for aesthetic use since 2002. Since then, clinical studies and expert use have informed our understanding of how BoNT exerts its clinical effect and the practical use of this product across a number of aesthetic applications. This review discusses the clinical properties and characteristics of abobotulinumtoxinA, which patients are suitable for its use, and how it can be utilized to treat facial rhytides.

Sleep Wrinkles: Facial Aging and Facial Distortion During Sleep.

Wrinkles are just one indicator of facial aging, but an indicator that is of prime importance in our world of facial aesthetics. Wrinkles occur where fault lines develop in aging skin. Those fault lines may be due to skin distortion resulting from facial expression or may be due to skin distortion from mechanical compression during sleep. Expression wrinkles and sleep wrinkles differ in etiology, location, and anatomical pattern. Compression, shear, and stress forces act on the face in lateral or prone sleep positions. We review the literature relating to the development of wrinkles and the biomechanical changes that occur in response to intrinsic and extrinsic influences. We explore the possibility that compression during sleep not only results in wrinkles but may also contribute to facial skin expansion.

OnabotulinumtoxinA for Treatment of Moderate to Severe Crow's Feet Lines: A Review.

Lateral canthal lines or crow's feet lines (CFL) may be treated with onabotulinumtoxinA. We identified several key concepts important to understanding the use of onabotulinumtoxinA for treatment of moderate-to-severe CFL. To contextualize and integrate data on the recommended dose and injection patterns of onabotulinumtoxinA for treatment of CFL, we summarized data from pivotal clinical studies in the development of onabotulinumtoxinA for treatment of CFL. Data from key studies of onabotulinumtoxinA for CFL are presented. The efficacy and safety of onabotulinumtoxinA treatment of moderate-to-severe CFL were evaluated in 2 randomized, controlled phase 3 studies comprising 1362 patients. The 24U total dose of onabotulinumtoxinA used in these studies was based on a phase 2 dose-ranging trial. Two injection patterns were available to investigators; each involved 3 injection sites per side in the lateral orbicularis oculi muscle. A cross-sectional analysis of photographs from the phase 3 trials provided detailed information on the frequency of 4 distinct CFL patterns. In the primary efficacy analysis for each phase 3 trial, CFL responder rates were significantly greater with onabotulinumtoxinA vs placebo at day 30 (P< .001). Eyelid edema (1%) was the only adverse event reported in ≥ 1% of patients receiving onabotulinumtoxinA, occurring more frequently with onabotulinumtoxinA than with placebo. The studies showed that onabotulinumtoxinA is effective and generally well-tolerated for CFL treatment. Additionally, 2 different injection patterns allow physicians to tailor treatment based on a patient's CFL pattern.

Heterogeneity of crow's feet line patterns in clinical trial subjects.

BACKGROUND: Patterns of crow's feet lines (CFLs) vary among individuals. OBJECTIVE: To characterize distribution and predictors of CFL patterns. METHODS: Patterns of CFLs (full fan, lower fan, central fan, and upper fan) were evaluated at maximum smile and at rest from photographs of subjects with moderate-to-severe CFLs. Relationships between CFL pattern and severity, age, gender, and subject-reported outcomes were explored. RESULTS: Evaluations of 2,699 photographs from 1,392 subjects were conducted; 1,389 and 1,310 had evaluable CFL patterns at maximum smile and at rest, respectively. Lower-fan, central-fan, and full-fan patterns were identified in 28.4% to 34.7% at maximum smile and 27.7% to 33.9% at rest; upper fan was found in ∼5%. The pattern distribution of CFLs demonstrated a relationship to baseline CFL severity, age, and gender; full-fan and lower-fan patterns were more common in severe versus moderate CFL at maximum smile; full fan increased with age. Lower fan was more common in males. Subjects with full fan at maximum smile were most dissatisfied with their appearance and perceived themselves to look older versus other patterns. CONCLUSION: Baseline CFL severity, age, and gender may predict fan pattern. Patterns may progress with age from central to lower fan or full fan. Pattern heterogeneity of CFLs suggests that tailored treatment may be warranted.

A Randomized, Double-Blind Trial to Investigate the Equivalence of IncobotulinumtoxinA and OnabotulinumtoxinA for Glabellar Frown Lines.

BACKGROUND: IncobotulinumtoxinA and onabotulinumtoxinA are indicated for the temporary improvement in the appearance of glabellar frown lines (GFL). This is the first randomized direct comparator study to date, at the Food and Drug Administration-recommended dose of 20 units (U), for the treatment of GFL. OBJECTIVE: To investigate the dose equivalence of incobotulinumtoxinA (20 U) and onabotulinumtoxinA (20 U) for the treatment of moderate-to-severe GFL. MATERIALS AND METHODS: Prospective, randomized (1:1), double-blinded, parallel-group study in 250 females (18-50 years), employing a single treatment with incobotulinumtoxinA or onabotulinumtoxinA, followed by a 4-month observational period. RESULTS: At the primary efficacy endpoint (1 month after treatment), incobotulinumtoxinA was equivalent to onabotulinumtoxinA in the treatment of GFL at the 20 U dose within the prespecified ± 15% margin of equivalence. Efficacy remained similar between treatment groups through 4 months after treatment as assessed by the independent masked panel and the masked treating physicians. Patient satisfaction ratings were similar between groups and favorable (>90%) throughout. Both treatments were well tolerated. CONCLUSION: Equivalence was demonstrated at the primary endpoint between incobotulinumtoxinA and onabotulinumtoxinA in the treatment of GFL at the 20 U dose at 1 month. Similar efficacy and tolerability profiles were observed through 4 months after treatment.

Optimized Aesthetic Outcomes When Treating Glabellar Lines with Botulinum Toxin Type A: GLO 3 + 2: A Precise Technique Based on Anatomy.

Good patient outcomes after treatment of the glabellar complex with botulinum toxin type A entail elimination of glabellar lines and maintenance of a natural eyebrow position. A precise injection technique that accurately targets the muscles that influence eyebrow position is required to reduce the risk of adverse aesthetic outcomes or unmasking an underlying eyelid ptosis. Here, we describe the glabellar lines optimization (GLO 3 + 2) injection anatomy technique, a precise five-point injection pattern that is based on current understanding of facial functional anatomy and which aims to minimize the risk of affecting nontargeted muscles. Injection sites above the brow or that do not target the precise location of the muscles in the glabellar complex are likely to inadvertently expose the frontalis to botulinum toxin type A and result in undesirable aesthetic outcomes. Because the frontalis is a strong determinant of aesthetic outcomes, it is important to consider the overall effects of the interactions between the eyebrow depressors and the opposing forces of the frontalis on brow outcomes in both the resting brow position and during dynamic brow movement.

The convergence of medicine and neurotoxins: a focus on botulinum toxin type A and its application in aesthetic medicine--a global, evidence-based botulinum toxin consensus education initiative: part I: botulinum toxin in clinical and cosmetic practice.

BACKGROUND: The U.S. Food and Drug Administration has approved four distinct formulations of botulinum toxin (BoNT) serotypes A and B (BoNTA and BoNTB) for medical use. These four products are indicated for many medical applications, but the three BoNTA formulations are the most widely used worldwide and are the only products approved for aesthetic use. The latest approval of a BoNTA with no complexing proteins (incobotulinumtoxinA) necessitates a review and discussion of differences between available formulations and the effect that these differences may have on clinical practice. OBJECTIVES: To review the history, science, safety information, and current and emerging applications of BoNT in clinical and cosmetic practice and to compare commercially available BoNTA formulations. METHODS AND MATERIALS: Publications, clinical trials, and author experience were used as a basis for an up-to-date review of BoNT and its use in human medicine. The similarities and differences between formulations are presented, and diffusion, spread, equivalency ratios, stability, and storage are discussed. RESULTS: Each commercial formulation has unique characteristics that may influence its use in aesthetic medicine. Familiarity with the similarities and differences between products will aid physicians in making patient care decisions. CONCLUSION: New formulations, emerging uses, and continued research into the science and uses of BoNTA will lead to increasingly refined therapeutic approaches and applications. Continued education is important for physicians to optimize use of the agent according to the most current evidence and approaches.

Current aesthetic use of abobotulinumtoxinA in clinical practice: an evidence-based consensus review.

The amount and complexity of scientific and clinical evidence for aesthetic use of botulinum neurotoxin type A (BoNT-A) has expanded rapidly in recent years, especially for abobotulinumtoxinA, necessitating reassessment of current knowledge about aesthetic use of abobotulinumtoxinA and other BoNT-A preparations. A committee of 13 plastic surgeons, facial plastic surgeons, and dermatologists engaged in a live discussion of information from a systematic literature review and an Internet-based survey of their beliefs and practices. The committee achieved consensus on most issues. It was concluded that doses of different BoNT-A preparations cannot be interconverted with a fixed ratio. The size of the "field of effect" is difficult to measure, and comparisons between preparations have yielded equivocal results. Nonresponse due to neutralizing antibodies appears exceedingly rare with currently available BoNT-A preparations and of little concern clinically. BoNT-A dose, injection depth, and injection technique should be adjusted according to the anatomic area being treated and each patient's individual characteristics and goals. Aesthetic use of BoNT-A has a good safety profile. Most adverse events are minor and related to the trauma of injection, although special care is needed in certain anatomic areas. Detailed recommendations for treatment of different anatomic areas are presented. BoNT-A products are often used in conjunction with other treatment modalities (eg, fillers and resurfacing), but little agreement was reached on best practices. The findings reported in this consensus document may serve as a practical guide for aesthetic practitioners as they apply the latest knowledge about BoNT-A in providing their patients with optimal care.

Time to onset of response of abobotulinumtoxina in the treatment of glabellar lines: a subset analysis of phase 3 clinical trials of a new botulinum toxin type A.

BACKGROUND: A new botulinum neurotoxin type A formulation, abobotulinumtoxinA (BoNTA-ABO; Medicis Aesthetics Inc., Scottsdale, AZ), was approved in 2009 in the United States for treatment of moderate to severe glabellar lines in adults younger than 65. OBJECTIVE To determine onset of response based on participant assessments recorded from days 1 through 7. MATERIALS & METHODS: Time to onset was assessed as a secondary endpoint in four multicenter, double-blind, placebo-controlled, randomized phase 3 trials evaluating BoNTA-ABO efficacy. Participants received 50 to 80 U of BoNTA-ABO (n=1,160) or placebo (n=580) at five injection sites in the glabellar region. Participants self-evaluated and recorded first effects. RESULTS: Response on day 1 was 13.4% to 32.5% in participants receiving BoNTA-ABO and 3% to 7% in those receiving placebo. Integrated analysis of three studies showed that 19.7% of participants responded by day 1; median onset was 3 days for BoNTA-ABO and 15 days for placebo. Men responded less frequently in fixed-treatment studies than in the study in which doses were adjusted for muscle mass. CONCLUSIONS: Treatment with BoNTA-ABO demonstrates significantly greater reduction in glabellar lines than placebo. Improvement was seen as early as 24 hours, with median time to onset of 2 to 4 days.

High-intensity focused ultrasound effectively reduces waist circumference by ablating adipose tissue from the abdomen and flanks: a retrospective case series.

BACKGROUND: Currently available technologies for performing aesthetic body sculpting are either noninvasive but require multiple treatments to achieve relatively superficial effects or very effective but also invasive and sometimes associated with serious complications. A new, noninvasive alternative is to ablate adipose tissue using high-intensity focused ultrasound (HIFU). When focused within subcutaneous adipose tissue, HIFU quickly raises the local temperature, resulting in instantaneous cell death via coagulative necrosis within the targeted area but no damage to the surrounding tissue. METHODS: A new HIFU device, the LipoSonix system (Medicis Technologies Corporation, Bothell, WA, USA), was used by our clinic staff to reduce waist circumference via removal of excess adipose tissue from the anterior abdomen and flank areas. This report describes the results of a retrospective chart review of patients at one clinic who underwent HIFU treatment of the anterior abdomen and flank areas. RESULTS: A total of 85 men and women with a mean age of 43.8 years underwent a single HIFU treatment session. The time required to complete treatment was approximately 1 to 1.5 h. Using a mean energy level of 134.8 J/cm(2) and a focal depth of 1.1 to 1.6 cm, the waist circumference was decreased by an average of 4.6 cm after 3 months. Of the 85 patients, 10 (11.8%) reported adverse events including prolonged tenderness (n = 3), ecchymosis (n = 3), hard lumps (n = 2), edema (n = 1), and pain (n = 1), which resolved spontaneously. CONCLUSIONS: The authors conclude from their experience that HIFU represents a safe and effective means for performing noninvasive body sculpting.

An analysis of efficacy data from four phase III studies of botulinum neurotoxin type A-ABO for the treatment of glabellar lines.

BACKGROUND: A new formulation of a botulinum neurotoxin type A (BoNTA-ABO; Dysport [abobotulinumtoxinA], Medicis Aesthetics, Scottsdale, AZ) has recently been approved in the United States for the treatment of moderate to severe glabellar lines. OBJECTIVE: We describe the results of four phase III studies of BoNTA-ABO for the treatment of glabellar lines. METHODS: Of the four studies reported here, three were double-blind, multicenter, randomized, placebo-controlled studies and one was an open-label extension study. A second phase III, open-label extension study is ongoing. Studies enrolled ethnically diverse, healthy adults with glabellar lines of at least moderate severity at maximum frown. Patients were followed for up to 180 days after treatment. The fixed-dose, single treatment study randomized 158 patients to receive placebo or a single 50-unit BoNTA-ABO dose. The fixed-dose, repeat treatment study enrolled 311 patients to assess treatment following repeat BoNTA-ABO treatment of 50 units. A variable-dose study randomized 816 patients to receive placebo or a single variable dose (50 to 80 units, based on gender and muscle mass assessment). The fourth phase III study was open-label to evaluate repeat dosing (50 units). Clinical evaluations were performed on days 14 and 30, and monthly thereafter. Primary efficacy endpoints were based on the investigators' and patients' assessment of glabellar line severity at day 30 using wrinkle severity rating scales. Responders were defined as patients who had a composite 2+ grade improvement in wrinkle severity, meaning that a patient had a baseline Glabellar Line Severity Scale (GLSS) score of 2 (moderate glabellar lines) and a day 30 GLSS score of 0 (no glabellar lines/none), or a baseline GLSS score of 3 (severe glabellar lines) and a day 30 GLSS score of 0 (no glabellar lines/none) or 1 (mild glabellar lines), for both the blinded investigator's and patient's assessments. RESULTS: Patients (1116 total; 720 BoNTA-ABO, 396 placebo) treated with BoNTA-ABO received 50 to 80 units. The median duration of response was 85 days for fixed dosing and 109 days for variable dosing. Similar efficacy occurred at doses adjusted for gender and muscle mass, although male patients required higher doses than female patients in the variable-dose study. Responses appeared as early as 24 hours, with a median time to onset of three days. The open-label extension study evaluated 1200 patients for 13 months. Maintenance of efficacy was seen after multiple treatment cycles, indicating that patients did not develop a tolerance. A second open-label study is ongoing and is not included in this report. CONCLUSIONS: BoNTA-ABO significantly improved moderate to severe glabellar lines compared with placebo, with onset of effect seen as soon as 24 hours after treatment and a median duration of effect of 85 and 109 days for fixed and variable dosing, respectively.