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.

Comparison of Hyaluronidase-Mediated Degradation Kinetics of Commercially Available Hyaluronic Acid Fillers In Vitro.

BACKGROUND: The ability to degrade hyaluronic acid (HA)-based fillers with hyaluronidase allows for better management of adverse effects and reversal of suboptimal treatment outcomes. OBJECTIVES: The aim of this study was to compare the enzymatic degradation kinetics of 16 commercially available HA-based fillers, representing 6 manufacturing technologies. METHODS: In this nonclinical study, a recently developed in vitro multidose hyaluronidase administration protocol was used to induce degradation of HA-based fillers, enabling real-time evaluation of viscoelastic properties under near-static conditions. Each filler was exposed to repeated doses of hyaluronidase at intervals of 5 minutes to reach the degradation threshold of G' ≤ 30 Pa. RESULTS: Noticeable differences in degradation characteristics were observed based on the design and technology of different filler classes. Vycross fillers were the most difficult to degrade and the Cohesive Polydensified Matrix filler was the least difficult to degrade. Preserved Network Technology products demonstrated proportional increases in gel degradation time and enzyme volume required for degradation across the individual resilient hyaluronic acid (RHA) products and indication categories. No obvious relationship was observed between gel degradation characteristics and the individual parameters of HA concentration, HA chain length, or the degree of modification of each filler when analyzed separately; however, a general correlation was identified with certain physicochemical properties. CONCLUSIONS: Manufacturing technology was the most important factor influencing the reversibility of an HA product. An understanding of the differential degradation profiles of commercially available fillers will allow clinicians to select products that offer a higher margin of safety due to their preferential reversibility.

Effectiveness and Safety of Resilient Hyaluronic Acid (RHA) Dermal Fillers for the Correction of Moderate-to-Severe Nasolabial Folds in People of Color: Post Hoc Subgroup Analyses of US Pivotal Clinical Data.

BACKGROUND: People of color (POC) are often underrepresented in clinical studies evaluating the safety and effectiveness of aesthetic products, including hyaluronic acid (HA) fillers, for which there is to date limited clinical data in POC. OBJECTIVES: The aim of this study was to assess the safety and effectiveness of a new line of dynamic resilient HA fillers (RHA; Revance, Nashville, TN) for treating moderate-to-severe nasolabial folds (NLFs) in POC vs non-POC. METHODS: Post hoc subgroup analyses compared the efficacy and safety of POC vs non-POC subjects treated with RHA2, RHA3, or RHA4 for correction of moderate-to-severe NLFs in the pooled per-protocol population (N = 217) in 2 clinical trials. Evaluated population cohorts were classified by Fitzpatrick skin type (FST) (high FST [IV-VI] vs low FST [I-III]) and by subject-reported race (non-White vs White) relative to baseline at 6, 9, 12, and 15 months. RESULTS: POC consistently showed greater improvement in wrinkle severity and higher responder rates compared with non-POC, which reached statistical significance at several measured time points. Global Aesthetic Improvement Scale scores and subject satisfaction ratings were similar for POC and non-POC and remained high throughout the course of the study. Treatment-related adverse event rates were generally lower for high FSTs vs low FSTs, with no reported cases of keloidal scarring. CONCLUSION: The RHA line of dynamic fillers is well tolerated and effective for the correction of moderate-to-severe NLFs in POC and can be confidently used in this important and growing patient population.See the abstract translated into Hindi, Portuguese, Korean, German, Italian, Arabic, Chinese, and Taiwanese online here: https://doi.org/10.1093/asj/sjad251.

Biochemical Stability and Microbial Control of Reconstituted DaxibotulinumtoxinA-lanm for Injection.

DaxibotulinumtoxinA-lanm for injection (DAXI) is a unique US Food and Drug Administration-approved product comprising daxibotulinumtoxinA and a stabilizing excipient peptide (RTP004). DAXI has a longer-labeled shelf life (72 h) following reconstitution than other botulinum toxin type A products. Here, we report the stability and microbial control of reconstituted DAXI when stored at 2 °C-8 °C over a period of 36 days (Study 1) and 7 days (Study 2) following reconstitution with unpreserved or preserved saline. The pH and biological activity of reconstituted DAXI in the 50 U/vial and 100 U/vial formats remained stable at the final assessed time point in both preserved and unpreserved saline when refrigerated (2 °C-8 °C). No changes in recoverable 150 kDa neurotoxin (measured by enzyme-linked immunosorbent assay) were observed over 6 days of refrigeration. Bacterial growth or pathogen proliferation was not observed in DAXI reconstituted in preserved or unpreserved saline in both studies.

A technology evaluation of the atypical use of a CPP-containing peptide in the formulation and performance of a clinical botulinum toxin product.

INTRODUCTION: Cell-penetrating peptides (CPPs), are small peptides that facilitate cytosolic access and, thus, transport of therapeutic macromolecules to intracellular sites when conjugated to cargo proteins. As with all new delivery platforms, clinical development of CPP-containing therapeutics has faced considerable challenges. AREAS COVERED: RTP004 is a novel, 35-amino acid, bi-CPP-containing excipient that binds noncovalently with its cargo (botulinum toxin type A) rather than conjugated as a fusion protein. An RTP004-containing neurotoxin formulation, daxibotulinumtoxinA-lanm for injection (DAXI), has recently been approved by the FDA. The formulation and pharmacological characteristics of RTP004 and the efficacy and safety of the RTP004-neurotoxin formulation are discussed. EXPERT OPINION: RTP004 is a highly positively charged lysine- and arginine-rich structure that provides formulation stability, preventing self-aggregation of the cargo protein and adsorption to container surfaces. The presence of RTP004 in the formulation also appears to increase presynaptic binding of the neurotoxin, reduces post-injection diffusion, and thus facilitates an increase in the cleavage of the intracellular substrate for the botulinum toxin, likely through enhanced cellular uptake. The RTP004-neurotoxin formulation is the first CPP-containing product approved for clinical use. The potential for RTP004 to facilitate other therapeutic cargo molecules requires further research.

Bridging the Gap: Sustained Treatment Effect of Glabellar Lines With Twice-A-Year Treatment With DaxibotulinumtoxinA.

BACKGROUND: To achieve natural-looking outcomes when treating dynamic lines with botulinum toxin (BoNT), retreatment must be timed such that the patient maintains a relatively constant aesthetic outcome. Although first-generation BoNT products require retreatment with 3- to 4-month frequency to avoid discontinuous correction, the average patient returns for treatment every 6 months, when these toxins have generally fully worn off. OBJECTIVE: To discuss the number of days a typical patient treated with daxibotulinumtoxinA for injection (DAXI) or legacy BoNT products will spend undertreated or uncorrected in a given calendar year. MATERIALS AND METHODS: Median time for maintaining glabellar lines in the "none" or "mild" severity range was compared for approved doses of onabotulinumtoxinA (ONA; 120 days) and DAXI (168 days). RESULTS: The average patient treated with 40U of DAXI every 6 months can expect to be uncorrected (with "moderate" or "severe" glabellar lines) for 14.5 days between visits compared with 61.5 days for 20U of ONA. CONCLUSION: An extended duration BoNT product can be expected to create greater consistency in aesthetic outcome and minimize the discontinuous correction commonly seen with first-generation BoNT products for patients treated twice a year, without requiring a change in patient behavior regarding visit frequency.

Immunogenicity of DaxibotulinumtoxinA for Injection in Glabellar Lines.

DaxibotulinumtoxinA-lanm for injection (DAXI), a novel botulinum toxin type A formulation, contains a purified 150-kD core neurotoxin (daxibotulinumtoxinA) and proprietary stabilizing peptide (RTP004), and is approved for glabellar line treatment. As with any biologic product, DAXI may potentially be immunogenic and elicit unwanted antibody formation, possibly resulting in partial or complete treatment failure. The immunogenicity of DAXI was assessed in 2 double-blind, placebo-controlled, single-dose studies and an open-label safety study of up to 3 repeat treatments. Of the 2737 evaluable patients, none developed neutralizing antibodies to daxibotulinumtoxinA and 0.8% developed treatment-related nonneutralizing anti-daxibotulinumtoxinA-binding antibodies. Of evaluable patients exposed to RTP004 with either DAXI or placebo, 1.3% developed treatment-related anti-RTP004-binding antibodies, which were mostly transient. No patient developed binding antibodies to both daxibotulinumtoxinA and RTP004. All patients with treatment-related binding antibodies to daxibotulinumtoxinA or RTP004 achieved a clinical response (none or mild glabellar line severity) at Week 4 following each DAXI treatment cycle. The duration of clinical response was not different between treatment cycles when antibodies were detected vs when they were absent. Although the analysis population was small compared to the number of patients likely to receive repeated treatment in clinical practice, these results suggest that DAXI administration at the approved glabellar lines dose has low immunogenic potential and that nonneutralizing antibodies to daxibotulinumtoxinA or RTP004 occur infrequently and often transiently, and have no impact on clinical efficacy, safety, or duration of action. Real-world data encompassing larger numbers of patients is needed to substantiate these results.

Clinical Immunogenicity of DaxibotulinumtoxinA for Injection in Glabellar Lines: Pooled Data from the SAKURA Phase 3 Trials.

DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A product containing daxibotulinumtoxinA with a stabilizing excipient peptide (RTP004). DAXI immunogenicity was assessed in three phase 3 glabellar line studies (two placebo-controlled, single-dose studies and an open-label repeat-dose safety study). Binding antibodies to daxibotulinumtoxinA and RTP004 were detected by validated ELISAs. Samples positive for daxibotulinumtoxinA-binding antibodies were evaluated further for titer and neutralizing antibodies by mouse protection assay. Overall, 2786 subjects received DAXI and 2823 subjects were exposed to RTP004 as DAXI (n = 2786) or placebo (n = 37). Treatment-related anti-daxibotulinumtoxinA binding antibodies were detected in 21 of 2737 evaluable subjects (0.8%). No subject developed neutralizing antibodies. Treatment-related anti-RTP004 binding antibodies were detected in 35 (1.3%) of 2772 evaluable subjects. Binding antibodies were generally transient, of low titer (<1:200), and no subject had binding antibodies to both daxibotulinumtoxinA and RTP004. All subjects with treatment-induced binding antibodies to daxibotulinumtoxinA or RTP004 achieved none or mild glabellar line severity at Week 4 following each DAXI cycle, indicating no impact on DAXI efficacy. No subjects with binding antibodies to daxibotulinumtoxinA or RTP004 reported immune-related adverse events. This evaluation of anti-drug antibody formation with DAXI shows low rates of antibody formation to both daxibotulinumtoxinA and RTP004.

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.

Integrative Assessment for Optimizing Aesthetic Outcomes When Treating Glabellar Lines With Botulinum Toxin Type A: An Appreciation of the Role of the Frontalis.

Despite the perception that treatment of glabellar lines with botulinum toxin A is straightforward, the reality is that the glabellar region contains a number of interrelated muscles. To avoid adverse outcomes, practitioners need to appreciate how treatment of 1 facial muscle group influences the relative dominance of others. In particular, practitioners need to understand the independent role of the frontalis in eyebrow outcomes and the potential for negative outcomes if the lower frontalis is unintentionally weakened by botulinum toxin A treatment. In addition, practitioners must recognize how inter-individual variation in the depth, shape, and muscle fiber orientation among the upper facial muscles can affect outcomes. For optimal results, treatment of the glabellar complex requires a systematic and individualized approach based on anatomical principles of opposing muscle actions rather than a one-size-fits-all approach. This review provides the anatomical justification for the importance of an integrated assessment of the upper facial muscles and eyebrow position prior to glabellar treatment. In addition, a systematic and broad evaluation system is provided that can be employed by practitioners to more comprehensively assess the glabellar region in order to optimize outcomes and avoid negatively impacting resting brow position and dynamic brow movement.

Impact of Glabellar Injection Technique With DaxibotulinumtoxinA for Injection on Brow Position.

BACKGROUND: Precise injection technique is vital for avoiding suboptimal eyebrow position when treating glabellar lines with botulinum toxin type A. OBJECTIVES: The aim of this study was to evaluate the impact of glabellar injection technique on eyebrow position in patients treated with DaxibotulinumtoxinA for Injection (DAXI). METHODS: This retrospective post hoc analysis involved 60 adults who received a single treatment with DAXI 40 U to the glabella and had standardized facial photography. Median vertical and horizontal displacement of the brows (at rest) at baseline and 2 weeks after glabellar injection were measured. Brow position outcomes were evaluated by an oculoplastic surgeon and expert anatomist. Investigators were interviewed to ascertain individual injection techniques. RESULTS: Precise injection location and depth, and median resting brow position following treatment varied between investigators. Positive brow outcomes were achieved with deep DAXI injections into the medial corrugator, superficial lateral corrugator injections placed between the midpupil and lateral limbus, and deep midline procerus injections. Glabellar injection technique that more precisely targeted the corrugator muscles resulted in longer glabellar line treatment duration compared to a less targeted technique. Medial corrugator injections above the medial brow; lateral corrugator injections administered deeply or more medially, toward the medial third of the brow; and procerus injections superior to the inferomedial brow tended to be associated with suboptimal outcomes that were more apparent during dynamic expression. CONCLUSIONS: Aesthetically pleasing brow outcomes and greater duration of efficacy can be achieved with an injection pattern that precisely treats the anatomic location of the corrugator supercilii and procerus muscles, avoiding the frontalis.

Overview of DaxibotulinumtoxinA for Injection: A Novel Formulation of Botulinum Toxin Type A.

Botulinum toxin type A (BoNTA) products are widely used for therapeutic and aesthetic indications, but there is a need for longer-lasting treatments that maintain symptom relief between injections and reduce the frequency of re-treatment. DaxibotulinumtoxinA for Injection (DAXI) is a novel BoNTA product containing highly purified 150-kDa core neurotoxin and is the first to be formulated with a proprietary stabilizing excipient peptide (RTP004) instead of human serum albumin. The positively charged RTP004 has been shown to enhance binding of the neurotoxin to neuronal surfaces, which may enhance the likelihood of neurotoxin internalization. DAXI produces robust, extended efficacy across both aesthetic and therapeutic indications. In an extensive glabellar lines clinical program, DAXI showed a high degree of efficacy, a consistent median time to loss of none or mild glabellar line severity of 24 weeks, and median time until return to baseline of up to 28 weeks. In adults with cervical dystonia, DAXI at 125 U and 250 U significantly improved Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores, with a median duration of efficacy of 24 and 20 weeks, respectively, which compares favorably with the 12-14 weeks' duration reported for approved BoNTA products. Overall, DAXI was well tolerated, and the consistent extended duration of effect suggests that DAXI has the potential to improve the management of both aesthetic and therapeutic conditions.

Botulinum toxin is used to block the nerve signals that cause muscles to contract. Products containing botulinum toxin are commonly given by injection to treat muscle spasms (such as cervical dystonia, a painful condition where the neck muscles contract involuntarily) and for cosmetic treatment of frown lines. However, the effects of the currently approved botulinum toxin products typically wear off about 3­4 months after injection and so the injections must be repeated regularly. A new product called DAXI (DaxibotulinumtoxinA for Injection) has been developed. In this product, the botulinum toxin is formulated with a unique protein (called RTP004) that has been designed to help deliver the botulinum toxin to the nerve cells. Research suggests that the RTP004 protein in DAXI adheres the botulinum toxin to the nerves close to the injection site, potentially making its effect last longer. To date, DAXI has been studied in over 3800 patients. The studies have shown that DAXI is effective for treating neck spasms (cervical dystonia) and for reducing the appearance of frown lines. Importantly, the effects of DAXI lasted up to 6 months, which is longer than seen with other botulinum toxin products. The side effects seen with DAXI are consistent in nature and frequency with those seen with other botulinum toxin products. These findings suggest that DAXI can improve both medical and cosmetic treatments due to its longer-lasting effect.

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.

Prior Botulinum Toxin Treatment Does Not Impact Efficacy or Safety in Clinical Trials: Analysis of DaxibotulinumtoxinA for Injection in the SAKURA Program.

BACKGROUND: Pivotal studies of approved botulinum toxin type A (BoNTA) formulations for treatment of glabellar lines have mostly included treatment-naive participants, and the impact of prior BoNTA treatment on efficacy and safety is not well documented. OBJECTIVE: To evaluate whether prior BoNTA treatment affects efficacy, duration of response, and tolerability for treatment of glabellar lines. METHODS: Adults with moderate or severe glabellar lines treated with DaxibotulinumtoxinA for Injection (DAXI) or placebo from the randomized, double-blind SAKURA 1/2 trials and the open-label SAKURA 3 safety study were analyzed by prior BoNTA treatment status. Efficacy was evaluated using investigator and participant assessments. RESULTS: In this analysis, 609 participants (52.2% BoNTA-experienced) from the SAKURA 1/2 trials and 2,380 (38.0% BoNTA-experienced) from the SAKURA 3 study were evaluated. Proportion of participants with none or mild glabellar lines and duration of response were similar between the BoNTA-naive and BoNTA-experienced cohorts in both the DAXI and placebo groups. The incidence of adverse events was also comparable regardless of prior BoNTA treatment status. CONCLUSION: Efficacy and tolerability were similar with DAXI and placebo regardless of prior BoNTA treatment. Assuming an appropriate washout is observed, future BoNTA trials should enroll both treatment-experienced and treatment-naive participants to reflect clinical practice.

DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Efficacy Results From SAKURA 3, a Large, Open-Label, Phase 3 Safety Study.

BACKGROUND: DaxibotulinumtoxinA for Injection (DAXI) is botulinum toxin Type A formulated with a novel peptide excipient. Two pivotal, single-treatment, placebo-controlled trials demonstrated efficacy and safety for moderate or severe glabellar lines. OBJECTIVE: To further evaluate DAXI in a large, open-label, repeat-treatment study. METHODS: Subjects (n = 2,691) were enrolled from the preceding pivotal trials or de novo and received 40U DAXI. Those who received repeat treatments could be retreated when they returned to baseline on the Investigator Global Assessment-Frown Wrinkle Severity (IGA-FWS) and Patient FWS (PFWS) scales at/after 12 weeks and up to 36 weeks after treatment. RESULTS: High (>96%) response rates (none or mild severity) on the IGA-FWS scale were seen after each of the 3 treatments, with peak response between Weeks 2 to 4. At Week 24, ≥32% had a response of none or mild severity. Peak response rates of ≥92% were observed at Weeks 2 to 4 on the PFWS scale. The median duration for return to moderate or severe severity was 24 weeks. The safety profile was favorable and consistent with previous trials. CONCLUSION: DaxibotulinumtoxinA for Injection efficacy was highly consistent across treatment cycles. These results confirm the previously observed efficacy rates and duration of response.

A Large, Open-Label, Phase 3 Safety Study of DaxibotulinumtoxinA for Injection in Glabellar Lines: A Focus on Safety From the SAKURA 3 Study.

BACKGROUND: SAKURA 3 was a Phase 3, open-label, repeat-dose safety study of DaxibotulinumtoxinA for Injection (DAXI); a component of the largest Phase 3 clinical development program of an aesthetic neuromodulator in glabellar lines. OBJECTIVE: To evaluate the use of DAXI (40U) up to 3 treatments for moderate or severe glabellar lines. METHODS: Eligible subjects rolled over from the placebo-controlled trials (n = 477) or were de novo (n = 2,214) and received 1 to 3 treatments over a maximum of 84 weeks. Safety and efficacy were evaluated at least every 4 weeks up to Week 36 (Treatments 1 and 2) and Week 12 (Treatment 3). Select subjects could be retreated after Week 12 if glabellar lines returned to baseline. RESULTS: Safety results are reported for 2,691 subjects, of which 882 received a second treatment and 568 a third. Treatment-related adverse events (AEs) occurred in 17.8% of subjects, which were generally mild and resolved. No serious AEs were treatment-related. Eyelid ptosis occurred in 0.9% of treatments. Adverse events were consistent across treatments and no new safety signals were observed. CONCLUSION: The safety of DAXI in this large open-label safety study confirms the findings from the pivotal Phase 3 trials, providing reassurance in its overall safety profile.

Maximizing Panfacial Aesthetic Outcomes: Findings and Recommendations From the HARMONY Study.

BACKGROUND: Aesthetic medicine has evolved from targeting individual treatment areas to a global approach of panfacial rejuvenation. HARMONY was the first clinical study to systematically demonstrate positive physical and psychosocial impacts of panfacial treatment. OBJECTIVE: Provide evidence-based guidance on treatment strategies to help maximize outcomes in patients seeking panfacial rejuvenation. MATERIALS AND METHODS: Study sites with the lowest (n = 2) and highest (n = 2) improvements based on FACE-Q Satisfaction with Face Overall scores were analyzed to understand differences in treatment strategy that may contribute to incrementally greater patient satisfaction. RESULTS: The highest scoring sites exhibited greater improvement in all patient-reported outcomes and investigator-assessed measures related to dermal filler treatment compared with the lowest scoring sites. The highest sites favored lateral malar augmentation and used less volume medially versus the lowest sites. In the lower face, the highest sites used greater volumes and more HYC-24L than HYC-24L+. Initial treatment volumes were more conservative at highest than lowest sites; greater volumes were used by highest sites in touch-up treatments. CONCLUSION: Product usage trends common to the highest scoring sites (including injection volume, injection sites, and product selection) may provide guidance on best practices for a panfacial approach to aesthetic treatment to maximize patient satisfaction.

DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Results from Each of Two Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 3 Studies (SAKURA 1 and SAKURA 2).

BACKGROUND: DaxibotulinumtoxinA for Injection (DAXI) is a novel botulinum toxin type A formulation in clinical development. A phase 2 dose-ranging study identified an optimal dose and demonstrated efficacy with a median duration of 24 weeks. METHODS: In two phase 3, multicenter, randomized, double-blind, placebo-controlled studies (SAKURA 1 and SAKURA 2), subjects with moderate or severe glabellar lines at maximum frown were assigned randomly to receive placebo or 40 U of DAXI. Glabellar lines were evaluated at least every 4 weeks for at least 24 weeks until severity returned to baseline (≤36 weeks). RESULTS: Overall, 609 subjects were enrolled (DAXI, n = 405; placebo, n = 204). DAXI was significantly more effective than placebo in achieving the primary efficacy outcome (≥2-point improvement in glabellar line severity at maximum frown at week 4 according to both investigator and subject ratings): 73.6 percent versus 0.0 percent (SAKURA 1), and 74.0 percent versus 1.0 percent (SAKURA 2) (both p < 0.0001). Composite investigator and subject ratings of maximum frown after DAXI treatment showed that glabellar line severity of none or mild was maintained for a median of 24.0 weeks (SAKURA 1) and 23.9 weeks (SAKURA 2), and glabellar line severity did not return to baseline levels for a median of 27.7 and 26.0 weeks, respectively. DAXI was generally well tolerated, with the most common adverse events related to DAXI treatment being headache (SAKURA 1, 7.0 percent; SAKURA 2, 5.9 percent) and injection-site pain (5.0 percent and 2.4 percent, respectively). CONCLUSIONS: Results from both studies were highly consistent. DAXI may offer a prolonged duration of response (median, ≥24 weeks) and is generally well tolerated. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Racial and Ethnic Differences in Self-Assessed Facial Aging in Women: Results From a Multinational Study.

BACKGROUND: Racial/ethnic variations in skin structure and function may contribute to differential manifestations of facial aging in various races/ethnicities. OBJECTIVE: To examine self-assessed differences in facial aging in women by race/ethnicity and Fitzpatrick skin phototypes. METHODS: Women aged 18 to 75 years in the United States, Canada, the United Kingdom, and Australia compared their features against photonumeric rating scales depicting degrees of severity for 10 facial aging characteristics. Impact of race/ethnicity (black, Hispanic, Asian, and Caucasian) and skin phototypes on severity was assessed. RESULTS: In total, 3,267 women completed the study. Black women reported the least severe facial aging; Caucasian women reported the most severe facial aging, with Asian and Hispanic women falling between these groups. Similarly, women with a skin phototype V/VI reported lesser aging severity than women with phototypes I through IV. More than 30% of black women did not report the presence of moderate/severe aging of facial areas until 60 to 79 years; most Hispanics and Asians did not report moderate/severe facial aging until 50 to 69 years and Caucasians, 40 to 59 years. CONCLUSION: In this diverse sample, black women reported less severe aging of facial features compared with Hispanic, Asian, and Caucasian women. These results were supported by Fitzpatrick skin phototype analyses.