Efficacy and Safety of ATX-101 by Treatment Session: Pooled Analysis of Data From the Phase 3 REFINE Trials.

BACKGROUND: ATX-101 (deoxycholic acid injection) is the only injectable drug approved for submental fat (SMF) reduction. In the phase 3 REFINE trials, adults with moderate or severe SMF who were dissatisfied with the appearance of their face/chin were eligible to receive up to 6 treatment sessions with ATX-101 (2 mg/cm2) or placebo. Primary and secondary endpoints, evaluated at 12 weeks after last treatment, significantly favored ATX-101 supporting its efficacy for reducing SMF and the psychological impact of SMF, and increasing satisfaction with the appearance of the face/chin. OBJECTIVES: To evaluate the efficacy and safety of ATX-101 by treatment session. METHODS: This post hoc analysis used pooled data from the REFINE trials to evaluate efficacy endpoints and adverse events following each treatment session to further characterize the ATX-101 treatment response and safety profile. RESULTS: In both treatment groups, mean injection volume declined over subsequent treatment sessions, though more markedly in the ATX-101 group. The majority of ATX-101-treated patients achieved a ≥1-grade improvement in SMF within 2 to 4 treatment sessions based on either clinician or patient assessment. Furthermore, 19.1% of ATX-101-treated patients (vs 3.9% of placebo-treated patients) received fewer than 6 treatment sessions owing to patient satisfaction with treatment or lack of sufficient SMF for further treatment. In both treatment groups, the incidence/severity of common injection-site adverse events declined over subsequent treatment sessions. CONCLUSIONS: Although up to 6 treatment sessions were permitted in the REFINE trials, most ATX-101-treated patients achieved an improvement in SMF within 2 to 4 treatment sessions. Level of Evidence: 3.

A randomized, placebo-controlled, double-blind phase III trial investigating the efficacy and safety of incobotulinumtoxinA in the treatment of glabellar frown lines using a stringent composite endpoint.

BACKGROUND: A prospective, randomized, double-blind, multicenter, Phase III trial of incobotulinumtoxinA using new Food and Drug Administration endpoints. OBJECTIVE: To investigate the efficacy and safety of a single dose of incobotulinumtoxinA for the treatment of glabellar frown lines. MATERIALS AND METHODS: Two hundred seventy-one subjects with moderate to severe glabellar frown lines at maximum frown-as assessed by an investigator according to the facial wrinkle scale (FWS)-were randomized 2:1 to receive one treatment of 20 U of incobotulinumtoxinA or placebo, respectively, and assessed over 120 days. The primary efficacy variable was a composite endpoint consisting of patients who were 2-point or more responders at maximum frown on Day 30 according to the investigator's rating on the FWS, and 2-point or more responders at maximum frown on Day 30 according to the patient's assessment on a 4-point scale. Safety analyses were performed throughout the study. RESULTS: IncobotulinumtoxinA was statistically significantly more efficacious than placebo using a new rigorous composite endpoint (p < .0001). CONCLUSION: A single dose of 20 U of incobotulinumtoxinA is superior to placebo in the treatment of glabellar frown lines at Day 30 and is well-tolerated.

Safety and tolerability of high-intensity focused ultrasonography for noninvasive body sculpting: 24-week data from a randomized, sham-controlled study.

BACKGROUND: High-intensity focused ultrasonography (HIFU) is a nonsurgical, noninvasive method for body sculpting in nonobese patients. The technique ablates subcutaneous adipose tissue by causing molecular vibrations that increase tissue temperature and induce rapid cell necrosis. OBJECTIVES: The authors evaluate the long-term safety of a HIFU device for sculpting the abdomen and flanks. METHODS: Adults with subcutaneous abdominal fat ≥2.5 cm in thickness who met screening criteria were randomized to receive HIFU treatment of the anterior abdomen and flanks at 1 of 3 energy levels (3 passes per patient): 47 J/cm(2) (141 J/cm(2) total), 59 J/cm(2) (177 J/cm(2) total), or 0 J/cm(2) (no energy applied; sham control). Safety was assessed for 24 weeks and included laboratory testing, physical examinations, and documentation of adverse events. RESULTS: Adverse events (AE) included mild to moderate discomfort, ecchymosis, and edema, all of which were transient. There were no reports of scarring or burns and no clinically meaningful changes in lipid panel findings, inflammatory markers, or renal or hepatic function. Physical examination results were unremarkable. CONCLUSIONS: This HIFU device exhibited an AE profile similar to that of sham treatment. There were no significant changes from baseline in laboratory values, including lipid levels.

Randomized sham-controlled trial to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for noninvasive body sculpting.

BACKGROUND: High-intensity focused ultrasound presents a noninvasive approach to body sculpting for nonobese patients. The purpose of this study was to evaluate the safety and effectiveness of a high-intensity focused ultrasound device for sculpting of the abdomen and flanks. METHODS: Adults (aged 18 to 65 years) with subcutaneous abdominal fat greater than or equal to 2.5 cm thick who met screening criteria were randomized to receive high-intensity focused ultrasound treatment of the anterior abdomen and flanks at energy levels (a total of three passes each) of 47 J/cm (141 J/cm total), 59 J/cm (177 J/cm), or 0 J/cm (no energy applied, sham control). The primary endpoint was change from baseline waist circumference at the iliac crest level at posttreatment week 12. Subjective aesthetic assessments included the Global Aesthetic Improvement Scale and a patient satisfaction questionnaire. Safety assessments included adverse events, laboratory values, and physical examinations. RESULTS: For the primary endpoint, in the intent-to-treat population, statistical significance versus sham was achieved for the 59-J/cm (-2.44; p = 0.01) but not the 47-J/cm treatment group (-2.06 cm; p = 0.13). In a per-protocol population, statistical significance versus sham was achieved for both the 59-J/cm (-2.52 cm; p = 0.002) and the 47-J/cm treatment groups (-2.10 cm; p = 0.04). Investigator subjective measures of global aesthetic improvement and patient satisfaction also favored each active treatment versus sham. Adverse events included mild to moderate discomfort, bruising, and edema. Laboratory values and physical examinations were unremarkable. CONCLUSIONS: Treatment with this high-intensity focused ultrasound device reduced waist circumference and was generally well tolerated for noninvasive body sculpting. Reduction in waist circumference was statistically significant with both active treatments (per protocol). CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.(Figure is included in full-text article.).

Improvement in nasolabial folds with a hyaluronic acid filler using a cohesive polydensified matrix technology: results from an 18-month open-label extension trial.

BACKGROUND: Repeat treatments of nonpermanent dermal fillers are used in the long-term treatment of wrinkles and folds and to volumize. OBJECTIVE To determine the safety and effectiveness of a nonanimal-sourced hyaluronic acid (HA) (which uses a cohesive polydensified matrix (CPM) technology [CPMHA]) for the treatment of nasolabial folds (NLFs) during an 18-month open-label extension trial. METHODS AND MATERIALS: Ninety-five of 118 subjects continued with this optional open-label extension of a split-face, double-blind trial. All subjects received CPMHA in both NLFs at 24 weeks after treatment in this study and were assessed at weeks 32, 48, 72, and 96. Touch-ups were allowed for optimal correction. Safety was assessed according to reported adverse events (AEs) and serum antibody measurement. RESULTS: At all four post-week 24 time points, the severity of the NLFs showed a decrease from baseline on the Wrinkle Severity Rating Scale. The effects persisted in the majority (∼80%) of subjects without repeat treatment for at least one interval of 48 weeks. The study filler was well tolerated, with only one related AE (injection site bruising) reported. Little potential for immunogenic reactions was identified. CONCLUSION: This CPMHA is a well-tolerated and effective treatment for at least 48 weeks in the majority of subjects for the correction of moderate to severe NLFs with repeat injections given over an 18-month period.

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.

Techniques in facial fat grafting.

According to the author, autologous fat transplantation is an ideal technique to correct facial atrophy, providing a stable and potentially long lasting alternative to "off the shelf" fillers. Structural augmentation with fat involves multilayer blunt fat infiltration designed around concepts of volume expansion and resultant tissue shifting. The author has found that retention varies in different parts of the face and fat seems to "take" best in areas in which fat atrophy is the problem, such as in the cheek, periorbital area, and mandible. When fat is being used to replace bony remodeling or mucosal atrophy (both occur in the perioral area), retention can be unpredictable.

Reduction in facial photodamage by a topical growth factor product.

A topical gel containing a proprietary mixture of over 110 growth factors, cytokines, and soluble matrix proteins secreted by human dermal fibroblasts was evaluated for safety and efficacy in the treatment of mild to severe facial photodamage. In a double-blind study, 60 subjects were randomly assigned to receive either active gel or the vehicle and applied twice daily for 6 months along with a moisturizing cleanser and sunscreen. Efficacy (profilometry, photography, and clinical assessment) and safety (adverse event reporting) measures were evaluated at 0, 3, and 6 months. Treatment with the active gel for 3 months produced greater reduction in fine lines and wrinkles than the vehicle treatment as measured by objective and subjective assessment techniques. The results were either statistically significant (P < or = .05) or trending towards statistical significance (P < or = .1). This study demonstrates that addition of a topical formulation of growth factors and cytokines to a basic skin care regimen reduces the signs of photoaging.

Panfacial volume restoration with fat.

BACKGROUND: A careful look at the aging face shows it to consist of more than loose skin and rhytids. With aging, the face loses its anterior projection, with a resultant displacement of skin inferiorly. There is mimetic muscular accentuation and an abundance of deep grooves and shadows. In addition, fat redistributes in specific patterns in overweight versus lean individuals. OBJECTIVE: To restore the three-dimensional projection and overall shape of the face to more youthful contours and to eliminate shadowing and muscle to skin interactions. METHODS: Autologous fat is harvested with an open-tipped, blunt cannula under tumescent anesthesia. It is then transferred to 1 mL syringes for injection into the face under local anesthesia. Fat is woven into the deep tissues of the face using a small-bore blunt cannula. The entire face is addressed by filling one cosmetic unit at a time. Fat is anchored deep to the muscles, in the muscles, and subcutaneously depending on the anatomic site and desired result. RESULTS: Dramatic changes in contour are achieved with judicious placement of fat. Skin redraping and the interruption of muscle to skin interactions occur when autologous fat is infiltrated in small aliquots, with specific direction at appropriate tissue levels. Complications are rare and minor with this technique. CONCLUSIONS: Autologous fat is an excellent tool for replacing volume and restoring contour to the aging face.

Aggressive Acne Treatment.

In brief Too often acne treatment focuses on diminishing lesions without considering what an active patient really wants: completely clear skin. In addition to benzoyl peroxide cleansing and topical acne medication, a three-tier approach of oral agents often achieves clear skin regardless of the severity of acne. Tetracycline is the first line of treatment, followed by minocycline if the first drug is not effective. If these two antibiotics fail to clear the acne, isotretinoin can be highly effective-but patients need to know that the drug produces birth defects in almost all women who take the drug while pregnant.