Fredric S. Brandt

Hyaluronic acid gel fillers in the management of facial aging

Time affects facial aging by producing cellular and anatomical changes resulting in the consequential loss of soft tissue volume. With the advent of new technologies, the physician has the opportunity of addressing these changes with the utilization of dermal fillers. Hyaluronic acid (HA) dermal fillers are the most popular, non-permanent injectable materials available to physicians today for the correction of soft tissue defects of the face. This material provides an effective, non invasive, non surgical alternative for correction of the contour defects of the face due to its enormous ability to bind water and easiness of implantation. HA dermal fillers are safe and effective. The baby-boomer generation, and their desire of turning back the clock while enjoying an active lifestyle, has expanded the popularity of these fillers. In the US, there are currently eight HA dermal fillers approved for commercialization by the Food and Drug Administration (FDA). This article reviews the innate properties of FDA-approved HA fillers and provides an insight on future HA products and their utilization for the management of the aging face.

Evaluation of Variable-Dose Treatment with a New U.S. Botulinum Toxin Type A (Dysport) for Correction of Moderate to Severe Glabellar Lines: Results from a Phase III, Randomized, Double-Blind, Placebo-Controlled Study

Background: In April, the U.S. Food and Drug Administration approved a new U.S. formulation of botulinum neurotoxin type A (Dysport; Medicis Aesthetics, Inc., Scottsdale, Ariz.). This formulation has demonstrated inhibition of glabellar lines at a 50-unit dose. Standard clinical practice is to adjust the dose based on muscle mass. Methods: Patients stratified by race/ethnicity were randomized to receive a single treatment of Dysport administered in various doses or placebo. Dysport was administered in a total volume of 0.4 to 0.6 ml for women (50, 60, or 70 units) and 0.5 to 0.7 ml for men (60, 70, or 80 units), based on procerus/corrugator muscle mass. Efficacy was assessed by a blinded evaluator and patient self-evaluation on days 14, 30, 60, 90, 120, and 150 after treatment. Results: At day 30, 85 percent and 87 percent of Dysport-treated patients were responders as assessed by blinded evaluator and patient self-evaluation, respectively, compared with 3 percent and 5 percent of placebo-treated patients, respectively (p < 0.001). Median duration of effect was 109 days for Dysport versus 0 days for placebo (blinded evaluator) and 107 days for Dysport versus 0 days for placebo (patient self-evaluation). Response and duration of action were slightly higher in African American patients. The majority of treatment-emergent adverse events were mild or moderate in severity. Conclusion: A single treatment with Dysport, with the dose based on gender and muscle mass, is well tolerated and provides a greater and longer-lasting improvement in glabellar lines compared with placebo.

Randomized, Placebo‐Controlled Study of a New Botulinum Toxin Type A for Treatment of Glabellar Lines: Efficacy and Safety

BACKGROUND A new botulinum toxin type A (BoNT‐A) has been assessed in the United States for treatment of glabellar lines. In April 2009, the US FDA approved the Biologics License Application for a new US formulation of BoNT‐A (Dysport [abobotulinumtoxinA]; Medicis Aesthetics Inc., Scottsdale, AZ). OBJECTIVE To compare efficacy and safety of a single treatment of BoNT‐A with placebo in subjects with moderate to severe glabellar lines. METHODS AND MATERIALS One hundred fifty‐eight subjects with moderate to severe glabellar lines were randomized 2:1 to receive 50 U of BoNT‐A (n=105) or placebo (n=53). Responders were defined as having no or mild glabellar lines at 30 days posttreatment according to investigator and subject assessments (co‐primary endpoint) using the validated Glabellar Line Scale Score at maximum frown. Subject diaries were used to document onset of effect. When conducting the research, the authors conformed to the ethical guidelines of the 1975 Declaration of Helsinki. RESULTS According to investigator assessment, the proportion of responders to BoNT‐A at Day 30 was 89.5%, versus 7.5% for placebo (p<.001); according to subject assessment, the proportion of responders was 75.7%, versus 9.8% for placebo (p<.001). CONCLUSION A single treatment with BoNT‐A (50 U) was significantly superior to placebo in the correction of moderate to severe glabellar lines, with comparable tolerability. Medicis Aesthetics, Inc. provided funding and the material Dysport for this study. Dr. Baumann is a consultant and advisory board member for the both Medicis and Allergan.

Twelve-month persistency of a novel ribose-cross-linked collagen dermal filler.

BACKGROUND The porcine collagen–derived dermal filler Dermicol-P35 (Evolence, Colbar LifeScience Ltd, Herzliya, Israel) has low immunogenicity and the potential to provide a long-lasting corrective response for soft-tissue contour deficiencies and deformities. OBJECTIVE The objective was to assess the persistence of the corrective response with Dermicol-P35 up to 12 months after obtaining an optimal cosmetic result (OCR) in a randomized, multicenter study comparing the efficacy and safety of Dermicol-P35 with the hyaluronic acid (HA) filler Restylane (Medicis Pharmaceutical Co.). METHODS & MATERIALS Subjects with moderate to deep nasolabial wrinkles (n=149) were randomized to injections of either Dermicol-P35 or HA on one side of the face and the alternative preparation on the contralateral side. If necessary, one touch-up injection could be given after 2 weeks to obtain an OCR. RESULTS Although the mean Modified Fitzpatrick Wrinkle Scale score increased gradually after achieving the OCR with Dermicol-P35, 95.3 and 76.5% of subjects, respectively, met the criteria for persistence of the corrective response after 9 and 12 months. Persistency rates were similar regardless of the requirement for a touch-up injection at Week 2. No unexpected, severe, or serious injection-related adverse events were experienced. CONCLUSION The effectiveness of Dermicol-P35 appears to be maintained for up to 1 year after achieving an OCR, both for touch-up and for non–touch-up subjects.

A randomized study of the efficacy and safety of injectable poly-L-lactic acid versus human-based collagen implant in the treatment of nasolabial fold wrinkles

BACKGROUND Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable, biocompatible polymer device. OBJECTIVE We sought to compare the efficacy and safety of injectable PLLA with human-derived collagen in treating nasolabial fold wrinkles. METHODS In this randomized, evaluator-blinded, parallel-group, multicenter study, subjects received injectable PLLA (n = 116) or collagen (n = 117) injections (1-4 visits, 3-week intervals). Wrinkle Assessment Scale scores were calculated at screening; posttreatment week 3; months 3, 6, 9, and 13 (injectable PLLA or collagen groups); and months 19 and 25 (injectable PLLA group). Safety data were obtained from subject interviews and case report forms. RESULTS Injectable PLLA significantly improved mean Wrinkle Assessment Scale scores (all time points, P < .001). Improvements (up to 25 months after last treatment) were significantly greater (P < .001) than with collagen for posttreatment months 3 to 13. LIMITATIONS Mostly white women and subjects with Fitzpatrick skin types II and III were included. CONCLUSION Injectable PLLA provides well-tolerated, effective, and long-lasting (up to 25 months) nasolabial fold wrinkle correction.

Efficacy and Safety Evaluation of a Novel Botulinum Toxin Topical Gel for the Treatment of Moderate to Severe Lateral Canthal Lines

BACKGROUND Botulinum toxin type A (BoNTA) is commonly injected to treat facial wrinkles. Complications include pain, erythema, bruising, and potential infection. RT001 Botulinum Toxin Type A Topical Gel (RT001) is under development for the treatment of lateral canthal lines (LCLs). OBJECTIVE To assess the efficacy and safety of RT001 for the treatment of LCLs using a randomized, double‐blind, repeat‐dose, placebo‐controlled study design. METHODS & MATERIALS Healthy adult subjects were randomized to receive RT001 (N=19) or placebo (N=17) applied to their lateral canthal areas (LCAs). To evaluate safety of repeat exposure, treatment was administered at baseline and week 4. The primary efficacy measure was improvement in baseline LCL severity using the Investigators Global Assessment of Lateral Canthal Line at Rest (IGA‐LCL) Severity Scale. RESULTS At 8 weeks, 19 (50%) LCAs treated with RT001 showed a 2‐point or greater improvement in baseline IGA‐LCL severity, versus none (0%) of the placebo‐treated subjects (p<.001); 36 (94.7%) LCAs treated with RT001 showed a 1‐point or more improvement in baseline IGA‐LCL severity, versus five (14.7%) placebo‐treated LCAs (p<.001). There were no treatment‐related adverse events. CONCLUSION RT001 was well tolerated and demonstrated an improvement in LCLs. This study was sponsored by Revance Therapeutics, Inc., Newark, CA.

Cosmeceuticals: current trends and market analysis.

The desire to maintain a youthful image combined with an emerging global market with disposable income has driven the development of many new industries. The cosmeceutical industry is based on the development and marketing of products that lie between cosmetics and pharmaceuticals. Today, there are over 400 suppliers and manufacturers of cosmeceutical products, and the industry is estimated to grow by 7.4% by 2012. Although a number of products advertise predictable outcomes, the industry is largely unregulated and any consumers of cosmeceutical products should consult a dermatologist prior to use. This review will provide a snapshot of the current trends of this industry and provide an analysis of this multi-billion dollar market.

Systematic review of clinical trials of small- and large-gel-particle hyaluronic acid injectable fillers for aesthetic soft tissue augmentation.

BACKGROUND Hyaluronic acid (HA) is the most frequently injected filler for soft tissue augmentation in the United States. OBJECTIVE To systematically review published evidence for aesthetic use of small‐ and large‐gel‐particle HA. METHODS AND MATERIALS Clinical data on anatomic area, level of evidence, patient population, trial design, endpoints, efficacy, and safety were extracted from PubMed. RESULTS Fifty‐three primary clinical reports were analyzed. The highest‐quality efficacy evidence was for the nasolabial folds (NLFs), with 10 randomized, blind, split‐face, comparative trials. Several randomized, blind trials supported treatment of the glabella, lips, and hands. Lower‐level evidence (from studies with nonrandomized, open‐label, or retrospective designs) was recorded for the nasojugal folds (tear troughs), upper eyelids, nose, infraorbital hollows, oral commissures, marionette lines, perioral rhytides, temples, and cheeks. Common adverse events (AEs) across anatomic areas were pain, bruising, swelling, and redness. Serious AEs were uncommon (8 events in 8 patients of 4,605 total patients) and were considered to be unrelated (7 events) or probably unrelated (1 event) to treatment. CONCLUSION The efficacy and safety of small‐ and large‐gel‐particle HA are well established for NLFs; evidence for the glabella, lips, and hands is more limited. Preliminary reports in other anatomic regions suggest efficacy without major complications.

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 investigators rating on the FWS, and 2‐point or more responders at maximum frown on Day 30 according to the patients 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.

Botulinum toxin for the treatment of neck lines and neck bands

Rejuvenation of the aging neck with botulinum toxin injections is a minimally invasive, safe, and effective treatment modality with a very high patient satisfaction rate. Treatments are usually started early in the aging process of the neck to prevent further degenerative changes and are performed thereafter at 4- to 6-month intervals. It is the ideal alternative to rhytidectomy when the patient is too young for face-lift surgery or for patients unwilling to take recuperation time. Furthermore, botulinum toxin therapy can be used to correct jowl and platysmal band asymmetry occurring after suboptimal rhytidectomy. Botulinum exotoxin should not be used in pregnant or lactating women or in patients with a known sensitivity to human albumin or with a history of neuromuscular disorders.