Progressive Improvement in Static Glabellar Lines After Repeated Treatment With DaxibotulinumtoxinA for Injection.

BACKGROUND: DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin in development that has demonstrated efficacy on dynamic glabellar lines. OBJECTIVE: To evaluate the effect of repeated DAXI treatment on static glabellar lines. METHODS: This post hoc analysis included adults with moderate or severe dynamic glabellar lines who were treated with 40U DAXI in the SAKURA clinical program. Glabellar line severity was evaluated through validated subject and investigator scales. RESULTS: Overall, 568 subjects received 3 DAXI treatments. Most subjects were White (92.3%) and female (85.7%). At baseline, 9.0% and 27.3% of subjects had no static glabellar lines based on subject and investigator assessment, respectively. Four weeks after DAXI Treatment Cycle 1, the proportion of subjects with no static glabellar lines increased to 57.9% and 64.8% based on subject and investigator assessment, respectively. At Week 4 after DAXI Treatment Cycles 2 and 3, the proportion further increased to 68.7% and 71.5%, respectively, based on subject assessment and 75.0% and 77.6% based on investigator assessment. CONCLUSION: Subjects who received repeated DAXI treatment showed progressive improvement in their static glabellar lines. The extended duration of therapeutic benefit with DAXI on dynamic glabellar lines likely provides a long period of muscle inactivity/hypoactivity, during which dermal remodeling can occur.

A Double-Blind, Placebo-Controlled, Phase 3b Study of ATX-101 for Reduction of Mild or Extreme Submental Fat.

BACKGROUND: ATX-101 (deoxycholic acid injection) is approved for reduction of moderate or severe submental fat (SMF). OBJECTIVE: To evaluate the efficacy and safety of ATX-101 in subjects with mild or extreme SMF. PATIENTS AND METHODS: Adults with mild or extreme SMF (based on clinician assessment) were randomized to receive ≤6 treatments with ATX-101 or placebo. Efficacy end points, evaluated at 12 weeks after last treatment, included percentage of subjects who achieved ≥1-grade improvement in SMF from baseline based on both clinician and patient assessment (composite CR-1/PR-1 response) as well as multiple subject-reported outcomes. Safety end points included change in skin laxity and incidence of adverse events. RESULTS: Overall, 61.3% of ATX-101-treated subjects versus 6.7% of placebo-treated subjects with mild SMF and 89.3% versus 13.3% of subjects, respectively, with extreme SMF achieved a composite CR-1/PR-1 response (p < .001 for both). ATX-101-treated subjects also reported higher levels of satisfaction and greater reductions in the psychological impact of SMF versus placebo-treated subjects regardless of baseline SMF severity. Skin laxity was unchanged or improved in most of the subjects. Adverse events were mainly mild/moderate, transient, and associated with the injection site. CONCLUSION: ATX-101 was efficacious and well tolerated for reduction of mild or extreme SMF.

A randomized, evaluator-blinded, controlled study of effectiveness and safety of small particle hyaluronic acid plus lidocaine for lip augmentation and perioral rhytides.

OBJECTIVE: To compare the safety and effectiveness of small particle hyaluronic acid plus lidocaine (SPHAL) versus no treatment for lip augmentation and perioral rhytides. METHODS AND MATERIALS: Adults scoring 1 (very thin) to 2 (thin) on the Medicis Lip Fullness Scale (MLFS) for upper and lower lips were randomized (3:1) to SPHAL or no treatment. Treatment success was an MLFS increase ≥1 point at Week 8. Secondary end points (MLFS score, independent photographic review, Global Aesthetic Improvement Scale, Wrinkle Assessment Scale for Upper Lip Lines) and safety were assessed throughout. RESULTS: Statistically significantly more patients were treatment successes with SPHAL (upper lip [80.2% vs 11.9%], lower lip [84.2% vs 18.4%], and upper and lower lips combined [76.1% vs 11.6%]), compared with no treatment (p <.001, all outcomes). Patients treated for both lip augmentation and perioral rhytides were rated as having an aesthetically meaningful improvement in perioral rhytides (p <.001). Most common treatment-emergent adverse events (AEs) included lip bruising, swelling, and pain and were mostly mild and transient in nature, without anticipated device AEs. CONCLUSION: Small particle hyaluronic acid plus lidocaine was effective and well tolerated and significantly more effective when both lips and perioral rhytides were treated, with improvement evident up to 6 months after treatment.

A review of the metabolism of 1,4-butanediol diglycidyl ether-crosslinked hyaluronic acid dermal fillers.

BACKGROUND: Cosmetic procedures are growing ever more common, and the use of soft tissue fillers is increasing. Practicing physicians need to be aware of the biological behavior of these products in tissue to enable them to respond to any safety concerns that their patients raise. OBJECTIVES: To provide an overview of the metabolism of 1,4-butanediol diglycidyl ether (BDDE)-crosslinked hyaluronic acid (HA) dermal fillers and to examine the safety of the resulting byproducts. METHODS: A review of available evidence was conducted. RESULTS: After reaction with HA, the epoxide groups of BDDE are neutralized, and only trace amounts of unreacted BDDE remain in the product (<2 parts per million). When crosslinked HA, uncrosslinked HA, and unreacted BDDE degrade, they break down into harmless byproducts or into byproducts that are identical to substances already found in the skin. CONCLUSION: Clinical and biocompatibility data from longer than 15 years support the favorable clinical safety profile of BDDE-crosslinked HA and its degradation products. Given the strength of the empirical evidence, physicians should be confident in offering these products to their patients.

OnabotulinumtoxinA: a meta-analysis of duration of effect in the treatment of glabellar lines.

BACKGROUND: Duration of effect of aesthetic treatments with botulinum toxin potentially influences subject satisfaction, treatment frequency, and annual costs, but quantitative outcomes for measuring duration of effect and correlations with subject satisfaction have yet to be fully elucidated. METHODS AND MATERIALS: Phase III clinical trials with similar designs were identified and their data pooled to ascertain duration of clinical effect of onabotulinumtoxinA in glabellar muscles. Duration was calculated using the Kaplan-Meier method for investigator-rated Facial Wrinkle scale (FWS) scores and subject global assessment (SGA) of glabellar lines. Responders were determined according to FWS score at maximum contraction and at repose 30 days after injection. RESULTS: Data from four trials with 621 onabotulinumtoxinA-treated (20 U) subjects were analyzed, 523 of these (84.2%) were identified as day-30 responders on the FWS at maximum contraction. Pooled median duration of effect for day-30 responders was 120 days for FWS at maximum contraction and 131 days for FWS at repose. Higher day 30 SGA scores were correlated with a greater duration of effect on dynamic, but not static lines. CONCLUSION: Treatment of glabellar lines with 20 U of onabotulinumtoxinA resulted in sustained clinical benefit for 4 months in more than 50% of responders; subject satisfaction increased with duration of effect.

A randomized, evaluator-blinded, controlled study of the effectiveness and safety of small gel particle hyaluronic acid for lip augmentation.

OBJECTIVES: To assess the effectiveness and safety of small gel particle hyaluronic acid (SGP-HA) for lip augmentation. METHODS: Adults (n = 180; aged 18-65) scoring 1 (very thin) to 2 (thin) on the 5-point validated Medicis Lip Fullness Scale (MLFS) for the upper or lower lip were randomized (3:1) to SGP-HA (≤1.5 mL/lip) or no treatment. Co-primary effectiveness end points were blinded-evaluator MLFS score for upper or lower lip at week 8. Secondary end points (MLFS score, independent photographic review, Global Aesthetic Improvement Scale [GAIS], safety assessments) were measured throughout the study. RESULTS: Statistically significantly more MLFS responders (≥1 grades of MLFS improvement at week 8) received SGP-HA (93% combined upper and lower lip responders [95% upper lip; 94% lower lip]) than no treatment (29% combined; p < .001). SGP-HA improved self-assessed combined lip GAIS (97% week 8; 74% week 24) significantly more than no treatment (0% throughout; p < .001). The SGP-HA group reported anticipated swelling (58%) and bruising (44%), 88% mild or 11% moderate severity, without unanticipated device adverse events. CONCLUSIONS: SGP-HA is highly effective and well tolerated for lip augmentation. Statistically significant improvement was evident based on the MLFS at 8 weeks, with visible results reported in the majority of participants 6 months after treatment.

Results of a randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a botulinum toxin type A topical gel for the treatment of moderate-to-severe lateral canthal lines.

BACKGROUND: Injections of botulinum toxin type A are commonly used to treat facial wrinkles; however, undesirable effects are associated with injections (e.g., pain, bruising, ptosis, immunogenicity, and needle aversion). To address these issues, RT001 Botulinum Toxin Type A Topical Gel is being developed for the treatment of lateral canthal lines. OBJECTIVES: To assess the safety and efficacy of RT001 for the treatment of lateral canthal lines in a randomized, double-blind, placebo-controlled study. MATERIALS & METHODS: Adult subjects were enrolled to receive a single treatment of RT001 (n=45) or placebo (n=45) applied topically in the lateral canthal area. The primary endpoint was the composite of the Investigator Global Assessment of Lateral Canthal Line Severity (IGA-LCL) and the Patient Severity Assessment of lateral canthal line severity (PSA) defined as a 2-point or greater improvement on both scales. RESULTS: At four weeks, 44.4 percent of subjects treated with RT001 achieved a 2-point or greater improvement on a rigorous composite of both the IGA-LCL and PSA scales compared to 0.0% for the placebo subjects (P<0.0001). At four weeks, 88.9 percent of subjects achieved clinically relevant improvement by investigator assessment. Adverse events were mild in severity and unrelated to study treatment. CONCLUSIONS: RT001 appears to be a safe and well-tolerated treatment for improvement of lateral canthal lines.

Development and validation of a new clinically-meaningful rating scale for measuring lateral canthal line severity.

BACKGROUND: Several scales have been employed for evaluating the effects of cosmetic treatments in the periorbital area. The Food and Drug Administration (FDA) has recently issued new recommendations specifying a rigorous process to validate new aesthetic scales. OBJECTIVES: The authors describe and validate a new clinical rating scale: the Investigator's Global Assessment of Lateral Canthal Line (IGA-LCL) severity scale. METHODS: The new FDA recommendations were utilized to validate the new scale. The first step was concept elicitation (based on direct input from clinicians, patients, and literature) and evaluation of content validity (appropriateness of concepts). The resulting five-point scale provided detailed descriptions of the lateral canthal lines (LCL), including quantitative assessment of LCL length and depth. Performance parameters, including intra- and interrater reproducibility and construct validity, were then evaluated in clinical studies. Finally, the scale's threshold for clinically-meaningful benefit and the ability of the scale to detect change were confirmed in two Phase 2b clinical studies involving a total of 270 subjects. RESULTS: Content validity was established and the IGA-LCL scale showed excellent interrater reliability (weighted Kappa = 0.89) and interrater reliability (weighted Kappa = 0.77; Kendall's coefficient of concordance = 0.89). In clinical trials, the scale was sensitive enough to detect clinically-meaningful one- and two-point changes in LCL severity following treatment with topical botulinum toxin type A (BoNT-A). The authors observed statistically-significant correlations between the physician-rated IGA-LCL results and patient-reported outcomes. CONCLUSIONS: The IGA-LCL scale was shown to be reliable, appropriate, and clinically meaningful for measuring LCL severity.

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.

Facial Soft-Tissue Fillers: Assessing the State of the Science conference---Proceedings report.

The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report summarizes the deliberations and key points made by the panel and presenters to the panel, and includes a summary of the panel's near-term and longer term recommendations for next steps to help guide future efforts to address the safety, efficacy, and effectiveness of facial soft-tissue fillers. This report represents the panel's assessment of the medical knowledge available on facial soft-tissue fillers at the time of the conference.

Facial Soft-Tissue Fillers conference: Assessing the State of the Science.

The American Academy of Dermatology and the American Society of Plastic Surgeons, with the support of other sister societies, conducted the Facial Soft-Tissue Fillers: Assessing the State of the Science conference in December of 2009. The American Academy of Dermatology and the American Society of Plastic Surgeons established a panel of leading experts in the field of soft-tissue fillers-from researchers to clinicians-and other stakeholders for the conference to examine and discuss issues of patient safety, efficacy, and effectiveness in relation to the approved and off-label use of soft-tissue fillers, and other factors, including the training and level of experience of individuals administering fillers. This report represents the systematic literature review that examines comprehensively the available evidence and gaps in the evidence related to soft-tissue fillers, to inform and support the work of the state-of-the-science conference panel. This evidence-based medicine review will serve as the foundation for future evidence-based medicine reports in this growing field.

12-Month controlled study in the United States of the safety and efficacy of a permanent 2.5% polyacrylamide hydrogel soft-tissue filler.

OBJECTIVE: To evaluate the safety and efficacy of a 2.5% polyacrylamide hydrogel in the aesthetic enhancement of nasolabial folds. METHODS AND MATERIALS: The safety and efficacy of a polyacrylamide hydrogel were compared with those of nonanimal stabilized hyaluronic acid (NASHA) in 315 subjects in a double-blind, randomized, multicenter, noninferiority trial with a 12-month follow-up. The primary efficacy end point was mean change in Wrinkle Assessment Scale (WAS) scores at 6 months. The primary safety end point was rate of serious adverse events (AEs) through 12 months after treatment. RESULTS: Polyacrylamide hydrogel was as effective as NASHA, and effectiveness persisted throughout the 12-month follow-up. Treatment-related AEs occurred with equal incidence; most were mild to moderate, transient, and related to injection procedure. One serious AE (infection) was thought to be related to treatment with polyacrylamide hydrogel; it resolved within 5 days after appropriate treatment. CONCLUSION: This 2.5% polyacrylamide hydrogel offers promise as a long-lasting soft tissue filler. It is well tolerated, as effective as NASHA in correction of nasolabial folds, and persistent. Longer evaluation is required to evaluate longer-term safety and demonstrate duration of effect beyond 12 months. This

The efficacy and safety of a new U.S. Botulinum toxin type A in the retreatment of glabellar lines following open-label treatment.

INTRODUCTION: A new U.S. Botulinum toxin type A (BoNT-A) has been shown to be safe and effective when administered once, but there is a paucity of clinical evidence regarding long-term use. OBJECTIVE: To evaluate the long-term efficacy and tolerability of repeated treatment with BoNT-A in the correction of moderate-to-severe glabellar lines. STUDY DESIGN/METHODOLOGY: Multicenter, phase 3, randomized, placebo-controlled, double-blind study comparing the efficacy of BoNT-A (50 units) with placebo upon re-treatment of glabellar lines following two-to-three cycles of open-label BoNT-A treatment in 311 patients. RESULTS: At endpoint, BoNT-A produced a significantly higher proportion of responders versus placebo. The incidence of treatment-emergent adverse effects (TEAEs) was slightly lower during additional treatment cycles; the frequency was comparable between BoNT-A and placebo groups. CONCLUSION: Multiple treatment cycles of BoNT-A were well tolerated in the majority of patients, and there was no tachyphylaxis seen during the study duration of up to 23 months.

Effect of injection techniques on the rate of local adverse events in patients implanted with nonanimal hyaluronic acid gel dermal fillers.

BACKGROUND: One question associated with dermal fillers is whether the rate and variability of local adverse events following treatment are related to injection technique and needle trauma or to the intrinsic chemical composition. OBJECTIVE: The objective was to determine if there is a relationship between dermal filler injection technique and the incidence of local adverse events. METHODS AND MATERIALS: A prospective, blinded, controlled study enrolled 283 patients who were randomized to receive midface volume correction of the nasolabial folds and oral commissures with the nonanimal-stabilized hyaluronic acid (NASHA) gel filler Restylane or Perlane (Medicis Pharmaceutical Corp.). Data were collected on multiple injection technique variables to assess adverse events. RESULTS: Injection techniques that increase the dissection of the subepidermal plane (e.g., fanlike needle use, rapid injection, rapid flow rates, and higher volumes) increased the incidence of local adverse events. Injection techniques that increase epidermal damage or subcutaneous exposure (e.g., multiple punctures or deep subcutaneous injection) had no effect on adverse events. Furthermore, single injection correction, depth of injection, and NASHA product injected had no effect on local adverse events. CONCLUSIONS: Local adverse events following injection with the NASHA gel fillers used in this study were related to investigator technique and not to differences in the intrinsic properties of the NASHA agents.

A quality rating scale for aesthetic surgical procedures.

BACKGROUND: Cosmetic dermatologic procedures offer the promise of visible aesthetic enhancement with minimal risk. While in recent years the number of available procedures has proliferated, there are few objective methods for evaluating the relative quality of these procedures for particular indications or specific patients. OBJECTIVE: (A) To develop a simple, easy-to-use numerical rating scale to assess the quality of cosmetic surgical procedures on a range of parameters pertaining to clinical efficacy and patient satisfaction; (B) to statistically validate the discriminative value of this rating scale. METHODS: (A) Patient and physician interviews were performed to elicit a list of factors that may collectively characterize the clinical efficacy and patient tolerability of cosmetic dermatologic procedures. A 0-100 point rating scale was developed based on these factors, with the face-validity of this scale checked by a group of patients and physicians; (B) Statistical analysis of the questionnaire was performed by asking 15 expert cosmetic dermatologic surgeons to use it to rate 23 common cosmetic dermatologic procedures, and analyzing the results. RESULTS: (A) An easy-to-use scale was constructed to assess the quality of cosmetic dermatologic procedures by rating the associated cost, risk, time (procedure and recovery), discomfort, results, and longevity of benefit. A "physician adjustment factor" was used to further increase the relevance of this 0-100 point scale for specific patients; (B) Repeated-measures analysis of variations (ANOVAs) performed on the data from the survey of experts demonstrated that this scale can be used to discriminate between common dermatologic procedures. The differences in mean subscores and total scores among procedures grouped by anatomic site and target lesion-type were significant at the level of P < .05. LIMITATIONS: Patient preferences exogenous to the rating scale may increase or decrease the suitability of specific procedures. CONCLUSIONS: Common cosmetic dermatologic procedures are of uniformly high quality, as per expert ratings on a systematic measure. This quality rating scale appears statistically valid and robust, given that expert raters assigned similar ratings to the same procedures but mean ratings were different across procedures. In the future, this quality rating scale can be used to assess novel interventions, and to help dermatologic surgeons faced with patient concern to optimally select among alternative procedures for a given indication.

Review of the use of botulinum toxin for hyperhidrosis and cosmetic purposes.

This article reviews the current status of dermatological uses for botulinum toxin type A (Botox), recently approved in the United States for treatment of glabellar wrinkles, and type B (Myobloc), approved for cervical dystonia. The respective formulations of Botox and Myobloc are described, and injection techniques and special considerations for administration in the treatment of dermatologic conditions are also discussed. The use of botulinum toxin injections for cosmetic treatment of movement-related facial lines and platysmal bands in the neck is reviewed, including injection procedures, efficacy, and potential complications. Recent developments in the use of botulinum toxins for the treatment of palmar and axillary hyperhidrosis are also described, comparing type A and type B results. Although direct comparisons between botulinum toxins for dermatologic applications are complicated by the lack of functional equivalence of the standard potency assays, appropriate dosing strategies for obtaining satisfactory clinical results using type B are being established, which will add to the experience already gained with type A. The diffusion characteristics of type B appear to show different and potentially advantageous clinical profiles in the treatment of crows' feet and hyperhidrosis compared with type A.

Hyperhidrosis and botulinum toxin A: patient selection and techniques.

Focal idiopathic excessive eccrine sweating presents most commonly as an affliction of three anatomically distinct area: the axillae, the palms and soles, and the upper face. The true incidence is not known, but about half of the patients referred to us with this condition have at least one first-degree relative similarly affected. Only a fraction of patients afflicted are thought to seek medical care because of the social stigma, lack of understanding on the part of medical providers as to the cause and nature of the problem, and, until now, lack of effective nonsurgical therapy. A large social sample is required to accurately measure both the incidence and the exact nature of the genetic influence.

Treatment of hyperhidrosis with botulinum toxin.

Focal idiopathic and episodic eccrine sweating of the axillae, palms, soles, and face troubles afflicted individuals with a social curse that can only be imagined by those whose hands or underarms dampen only occasionally. Although there is no accurate incidence in the epidemiology literature, it seems that about half of the patients who have presented to the author with this condition have at least one first-degree relative similarly affected. Social stigma, lack of understanding on the part of medical providers as to the cause and nature of the problem, and lack of effective therapy keeps most of these patients from seeking medical care. This article investigates the treatment of hyperhidrosis with botulinum toxin.