LetibotulinumtoxinA Attenuates the Psychological Burden of Glabellar Lines and Is Associated With High Subject Satisfaction in Phase 3 Clinical Trials.

BACKGROUND: Hyperfunctional glabellar frown lines can transmit facial miscues that adversely affect emotional communication, increase perceptions of age, and diminish self-esteem. OBJECTIVE: To evaluate the efficacy of letibotulinumtoxinA in mitigating the negative psychological impact associated with moderate to severe glabellar lines and to assess subject satisfaction with treatment outcome in the BLESS phase 3 clinical trials. MATERIALS AND METHODS: Baseline and posttreatment assessments were made using validated subject-administered instruments: Modified Skindex-16 Glabellar Line Quality of Life (GL-QoL) Scale, Facial Assessment and Cosmetic Evaluation Questionnaire (FACE-Q) Appraisal of Lines Between Eyebrows Scale, FACE-Q Age Appraisal Visual Analog Scale, and FACE-Q Satisfaction with Outcome Scale. An integrated analysis using pooled BLESS data was conducted on these secondary end points. RESULTS: Among enrolled and treated subjects ( N = 1,272), 85.5% had moderate to severe psychological impact at baseline. LetibotulinumtoxinA subjects experienced significant improvements compared with placebo on all measures. Mean improvement to Week 4 for the Modified Skindex-16 GL-QoL Scale overall score was -33.84 for letibotulinumtoxinA subjects compared with -1.37 for placebo subjects ( p < .001). Attenuation of psychological burden was highly correlated with improvement in glabellar line severity ( p < .0001). CONCLUSION: LetibotulinumtoxinA significantly improved the psychosocial burden associated with glabellar lines across all trials. Treated subjects experienced improved quality of life, younger perceived age, and satisfaction with treatment outcome.

Efficacy and Safety of LetibotulinumtoxinA in the Treatment of Moderate and Severe Glabellar Lines in Females 35 to 50 Years of Age: Post Hoc Analyses of the Phase 3 Clinical Study Data.

Background: Botulinum toxin type A (BoNT-A) injections continue to be widely used as a common treatment for both males and females. According to a recent survey conducted by the International Society of Plastic Aesthetic Surgeons, the majority of patients receiving these injections are females between the ages 35 and 50. Objectives: A post hoc analysis was conducted to examine whether there were variances in the effectiveness and safety of letibotulinumtoxinA for treating vertical glabellar lines between the broader female study population and a particularly defined group of female participants aged 35 to 50. Methods: For this post hoc analysis, data from females aged 35 to 50 were extracted and analyzed from the BLESS III study. In this Phase 3 clinical trial, 355 participants with moderate-to-severe glabella frown lines received either 20 U of letibotulinumtoxinA or a placebo. The study evaluated Glabella Line Severity (GLS) score, treatment onset, duration of effects, time to retreatment, and adverse events. A positive response was determined by achieving a GLS score of 0 or 1, as assessed by both patients and investigators, along with at least a 2-point improvement in GLS score relative to baseline at Week 4 after the injections. Results: Composite responder rates for patients aged 35 to 50 receiving active treatment were significantly higher than for the remaining female population receiving active treatment at Weeks 1, 2, and 4. Females aged 35 to 50 showed higher rates of GLS improvement of ≥1 at Weeks 1, 2, 4, 8, 12, 16, and 20 compared with the remaining female population receiving active treatment. At Week 4, a higher percentage of females aged 35 to 50 achieved a GLS score of 0 upon maximum frowning compared with the remaining females. Females aged 35 to 50 had a shorter median time to onset of GLS improvement compared with the remaining female population. Safety assessments showed a low incidence of treatment-related adverse events in females aged 35 to 50. Conclusions: LetibotulinumtoxinA showed significantly higher response rates in females aged 35 to 50 compared with other female patients at Weeks 1, 2, and 4. Response rates remained higher up to Week 16. The treatment demonstrated efficacy and safety in treating vertical glabellar lines in this patient group.

Safety and Duration of Effect of 40U PrabotulinumtoxinA-xvfs for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients: A Phase II, Multi-Center, Randomized, Double Blind, Active-Controlled Trial.

BACKGROUND: Extending the duration of effect of botulinum toxins - by administering doses beyond those of the approved labels - has been an area of increasing interest in the field of aesthetics. OBJECTIVES: To investigate the safety and duration of effect of 40U prabotulinumtoxinA-xvfs (twice the approved dose and concentration) for the treatment of moderate-to-severe glabellar lines. METHODS: 154 adult patients were randomized 1:1:1 to a single treatment of either 40U prabotulinumtoxinA-xvfs (PRA 40, 5 injections of 8U/0.05 mL), or 20U of either prabotulinumtoxinA-xvfs (PRA 20) or onabotulinumtoxinA (ONA 20). Both 20U controls were administered as 5 injections of 4U/0.1 mL. Efficacy and safety were assessed on Days 2, 7 (by phone), 30 and every 30 days thereafter up to 365 days or until the patient had returned to Baseline. The primary effectiveness endpoint was the duration of effect (estimated by Kaplan-Meier analysis), defined as the number of days from Treatment Day (Baseline) to the day that glabellar line severity at maximum frown by investigator assessment returned to the baseline value. RESULTS: Patients had a mean age of 47 years (20-72 years); 69.5% had severe glabellar lines at Baseline. Of the 36 adverse events, 32 (88.9%) were mild and 4 (11.1%) were moderate in severity; none were serious. The median durations of effect were estimated to be 183, 149 and 148 days for PRA 40-, PRA 20- and ONA 20-treated patients, respectively. CONCLUSIONS: In this Phase II pilot study, 40U prabotulinumtoxinA-xvfs was observed to be safe and had a duration of 6 months.

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.

Effect of Topical Platelet Extract Daily Serum as a Cosmetic Product to Reduce Facial Redness.

Objective: The primary objective of this pilot study was to demonstrate the benefits of topical human platelet extract (plated)™ serum for the improvement of persistent facial redness. Methods: This single-center, open-label pilot study evaluated six subjects using (plated)™ serum containing human platelet extract (HPE) with Renewosome™ technology twice daily for six weeks. The primary efficacy endpoint was a reduction in the Clinical Erythema Assessment (CEA) grade, and a reduction in Patient Subjective Assessment grade at six weeks. Secondary endpoints included an improvement in quality of life related to facial redness, and a reduction in redness by Mexameter™ spectrometry measurement. Safety data included monitoring for adverse events. Results: Topical HPE serum demonstrated a statistically significant improvement in facial redness at Week 9 when averaging the Mexameter™ spectrometry results across nine regions of the face (p=0.0052). The primary and secondary endpoints were achieved. CEA grade at Week 6 demonstrated that all subjects improved by at least one grade, while one subject improved by two grades. One patient reported dryness. No other adverse effects were observed. Limitations: Study limitations included a small sample size and lack of darker skin types (Fitzpatrick IV-VI). Conclusion: This study demonstrates that topical HPE with Renewosome™ technology provides statistically significant reduction in facial redness and is safe and well-tolerated.

A Randomized, Multicenter, Evaluator-blind Study to Evaluate the Safety and Effectiveness of VYC-12L Treatment for Skin Quality Improvements.

BACKGROUND: Skin quality may be assessed by degrees of skin smoothness, fine lines, and hydration. VYC-12L is a recently developed hyaluronic acid filler to improve skin quality. OBJECTIVE: This was a randomized, evaluator-blind study assessing safety and effectiveness of intradermal VYC-12L treatment for improving cheek skin smoothness, fine lines, and hydration. METHODS: Participants (≥22 years) with moderate-to-severe investigator-assessed Allergan Cheek Smoothness Scale (ACSS) scores were randomized in 2:1 ratio to receive VYC-12L or control (no treatment with optional treatment). Effectiveness was assessed 1 month after last injection (initial or touch-up) by a responder rate (≥1-grade improvement from baseline on both cheeks) using investigator-rated ACSS and Allergan Fine Lines Scale (AFLS), and tissue dielectric constant probe-measured skin hydration. Safety was evaluated throughout. RESULTS: Participants (VYC-12L, n = 131; control, n = 71) were 86.1% female with a median age of 58.0 years. At month 1, ACSS and AFLS responder rates were statistically significantly higher in the VYC-12L group (57.9%, 58.3%, respectively) than in the untreated controls (4.5%, 5.4%, respectively; p < .001). VYC-12L ACSS and AFLS responder rates remained consistent throughout the 6-month follow-up. Six participants reported treatment-related adverse events; none led to study discontinuation. CONCLUSION: VYC-12L is an effective, well-tolerated treatment for lasting improvement of cheek skin smoothness, fine lines, and hydration.

Patient Comfort, Safety, and Effectiveness of Resilient Hyaluronic Acid Fillers Formulated With Different Local Anesthetics.

BACKGROUND: Maximizing patient comfort during hyaluronic acid gel injection is a common concern that is usually addressed by selecting fillers with lidocaine. OBJECTIVE: Two randomized, double-blinded, split-face trials aimed to demonstrate noninferiority of specific hyaluronic acid fillers incorporating mepivacaine (RHA-M) versus their lidocaine controls, at providing pain relief. METHODS: Thirty subjects per trial received injections of RHA R -M versus RHA R , and RHA4-M versus RHA4, respectively, in the perioral rhytids (PR) and nasolabial folds (NLF). Pain was assessed on a visual analog scale; aesthetic effectiveness was evaluated with validated scales, and safety was monitored based on common treatment responses (CTRs) and adverse events (AEs). RESULTS: RHA-M fillers proved as effective as their lidocaine counterparts at reducing pain (noninferior, p < .0002 and p < .0001). Bilateral wrinkle improvement was measured both in the PR (-1.5 ± 0.6 points on each side) and in the NLF (-1.8 ± 0.6 and -1.9 ± 0.5 points) trials at one month, with virtually identical responder rates (≥96.7%). Common treatment responses and AEs were similar between treated sides, and none was clinically significant. CONCLUSION: Resilient hyaluronic acid fillers with either mepivacaine or lidocaine are equally effective at reducing pain during treatment and equally performant and safe for correction of dynamic facial wrinkles and folds.

A Randomized Trial to Assess Effectiveness and Safety of a Hyaluronic Acid Filler for Chin Augmentation and Correction of Chin Retrusion.

BACKGROUND: The chin is important for facial appearance, affecting overall balance and harmony of the face. The purpose of this study was to evaluate effectiveness of the hyaluronic acid filler Restylane Defyne for chin augmentation and correction of chin retrusion versus a no-treatment control. METHODS: Male and female subjects, aged 22 years or older, with mild to moderate chin retrusion, were randomized 3:1 to the hyaluronic acid filler Restylane Defyne ( n = 107) or no treatment ( n = 33). Assessments included live, blinded evaluations on a validated chin retrusion scale (Galderma Chin Retrusion Scale), aesthetic improvement (Global Aesthetic Improvement Scale), subject-reported FACE-Q Satisfaction with Chin, and safety follow-up. RESULTS: Galderma Chin Retrusion Scale responder rate (≥1 grade improvement) was higher for the hyaluronic acid filler Restylane Defyne (81 percent) than for control (6 percent) ( p < 0.001) at week 12, and remained higher at week 48 (74 percent versus 11 percent; p < 0.001). Aesthetic improvement rates were high throughout the study as reported by investigators (≥96 percent) and subjects (≥85 percent). Subject satisfaction was higher in the hyaluronic acid filler Restylane Defyne group than in the control group at week 12 ( p < 0.001). In the individual FACE-Q scale items, 87 to 98 percent of subjects were satisfied at week 12. Treatment-related adverse events were mild to moderate. CONCLUSIONS: The hyaluronic acid filler Restylane Defyne was safe and effective for augmentation of the chin region to improve the chin profile and associated with high aesthetic improvement and subject satisfaction. Effectiveness was sustained throughout 48 weeks. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Collagenase Clostridium Histolyticum-aaes for Treatment of Cellulite: A Pooled Analysis of Two Phase-3 Trials.

Background: Collagen-rich fibrous septae and subcutaneous adipose protrusions play a role in cellulite pathophysiology. Collagenase clostridium histolyticum-aaes (CCH-aaes) injection causes enzymatic release of septae to resolve cellulite depressions and create a skin smoothing effect. This analysis pooled data from two identically designed, phase-3, randomized, double-blind, placebo-controlled studies to examine the efficacy and safety of CCH-aaes. Methods: Adult women with moderate/severe cellulite (3-4 on Clinician Reported Photonumeric Cellulite Severity Scale and Patient Reported Photonumeric Cellulite Severity Scale) on the buttocks received up to three treatment sessions (Days 1, 22, and 43) of subcutaneous CCH-aaes 0.84 mg or placebo per treatment area. Composite and individual component response (≥2-level or ≥1-level improvement from baseline in Patient Reported Photonumeric Cellulite Severity Scale and/or Clinician Reported Photonumeric Cellulite Severity Scale) and additional patient-reported outcomes were determined at Day 71. Results: Analysis included 424 CCH-aaes-treated and 419 placebo-treated women. CCH-aaes-treated women were 5.9 times more likely than placebo-treated women to be ≥2-level composite responders at Day 71 (odds ratio [95% confidence interval], 5.9 [2.2-15.4]; P < 0.001). A significantly greater percentage of CCH-aaes-treated women versus placebo-treated women were ≥1-level composite responders at Day 71 (39.4% versus 14.6%; P < 0.001). Subgroup analyses indicated no apparent impact of Fitzpatrick skin type category and baseline cellulite severity (moderate/severe) on CCH-aaes efficacy. An inverse relationship between age and CCH-aaes response was observed in those with a body mass index less than 32 kg per m2. The most common adverse events with CCH-aaes were injection-site bruising and injection-site pain. Conclusion: CCH-aaes treatment significantly improved moderate-to-severe buttock cellulite appearance and was generally well tolerated.

Subject satisfaction and psychological well-being with escalating abobotulinumtoxinA injection dose for the treatment of moderate to severe glabellar lines.

BACKGROUND: Previous studies indicate that the efficacy and durability of a single AbobotulinumtoxinA (ABO) treatment for moderate to severe glabellar lines may be enhanced with increasing dose, while safety outcomes remain consistent with those of the licensed dose (50 U). AIMS: Evaluation of subject-reported indicators of treatment efficacy, satisfaction, and psychological well-being with ABO dose escalation. METHODS: A Phase 2, 36-week, multicenter, randomized, dose-ranging, double-blind, placebo-controlled study was conducted in adults with moderate to severe glabellar lines. Subjects received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Efficacy endpoints comprised subject-assessed improvement in line severity of ≥1-grade from baseline at maximum frown, global aesthetic improvement scale (GAIS) grade, FACE-Q™ appraisal of lines, psychological well-being and age, and subject satisfaction. RESULTS: The study included 399 subjects (88.2% were female). Respective responder rates (≥1-grade improvement) with ABO 50-125 U doses ranged between 96.3%-100% at Week 4, 65.0%-67.9% at Week 24, and 33.8%-44.4% at Week 36. GAIS responder rate and FACE-Q appraisal of lines showed a similar pattern of change. Satisfaction was high and psychological well-being was improved from Week 4 through Week 36, with natural, youthful, and refreshed appearance reported for all ABO doses. CONCLUSIONS: A single ABO treatment (dosed at 50-125 U) provided significant and sustained improvements in glabellar line severity over durations up to 36 weeks, versus placebo. Treatment satisfaction was high with all doses. Participants reported natural and youthful appearance, alongside improvements in psychological well-being.

Evaluation of five collagenase clostridium histolyticum-aaes injection techniques for the treatment of cellulite on the buttock or thigh.

BACKGROUND: Given differences in buttock versus thigh cellulite, collagenase clostridium histolyticum-aaes (CCH-aaes) injection technique may impact treatment effects at these sites. AIM: To evaluate efficacy and safety of 5 CCH-aaes injection techniques. METHODS: A phase 2A, open-label trial enrolled women with mild-to-severe cellulite (Clinician Reported Photonumeric Cellulite Severity Scale) on both buttocks or thighs. CCH-aaes 0.84 mg was administered as 12 injections in each of two buttock or two thigh treatment areas (total dose, 1.68 mg) during three treatment sessions (Days 1, 22, 43). On Day 1, women were sequentially assigned to: Technique A = shallow injection/3 aliquots; Technique B = shallow injection/1 aliquot; Technique C = deep injection/1 aliquot; Technique D = deep and shallow injections/5 aliquots; or Technique E = shallow injection/4 aliquots. Change from baseline in Hexsel Cellulite Severity Scale (CSS) depression depth (range, 0 [no depressions] to 3 [deep depressions]) was assessed at Day 71. Safety was evaluated via adverse events. RESULTS: Sixty-three women with buttock (n = 31) or thigh (n = 32) cellulite received ≥1 CCH-aaes dose. For buttock cellulite, CCH-aaes injection Technique A resulted in the greatest baseline-adjusted improvement in CSS score on Day 71 (least-squares mean, 1.17-point improvement). For thigh cellulite, CSS score improvement was greatest with Technique D (least-squares mean, 1.40-point improvement). CCH injection Techniques A, D, and E were associated with more favorable safety profiles than Techniques B and C. CONCLUSION: Different CCH-aaes injection techniques are required with buttock (Technique A) versus thigh (Technique D) cellulite to optimize treatment outcomes.

Injection Guidelines for Treating Midface Volume Deficiency With Hyaluronic Acid Fillers: The ATP Approach (Anatomy, Techniques, Products).

Midface rejuvenation is among the most valuable indications of hyaluronic acid dermal fillers, because malar projection and full upper cheeks significantly contribute to a youthful appearance. Hyaluronic acid fillers have evolved over the past 2 decades to meet specific clinical needs such as strong projection capacity and adaptability to facial dynamism. As a result, they now represent the treatment of choice for midface rejuvenation throughout age ranges by offering the potential for noninvasive treatment, immediate results, and minimal downtime. Because the 5-layered structure of the midface plays a central role in the human face, injecting the midface area may also indirectly improve other aesthetic concerns such as infraorbital hollowing and nasolabial folds. Nonetheless, midface rejuvenation requires a tailored treatment approach and a thorough knowledge of anatomy to minimize procedural risks and achieve natural-looking results. This article provides an extensive anatomical description of the midface and of the usual course and depth of vascular structures circulating nearby to delineate a treatment area and minimize procedural risks. Furthermore, considering the differential mobility and mechanical constraints of each layer of the midface, a multilayer treatment algorithm is proposed for adapting the treatment strategy to patient specificities (including age, gender, skin type, and morphology). Emphasis is also placed on desirable filler properties to create deep structural support on the one hand and accompany facial movement on the other hand.

Efficacy and Safety of Letibotulinumtoxin A in the Treatment of Glabellar Lines: A Randomized, Double-Blind, Multicenter, Placebo-Controlled Phase 3 Study.

BACKGROUND: Letibotulinumtoxin A (Hugel, Inc., Chuncheon, Republic of Korea and CROMA Pharma, Leobendorf, Austria) is a newly manufactured neurotoxin derived from Clostridium botulinum strain CBFC26. OBJECTIVES: The aim of this study was to assess the efficacy and safety of letibotulinumtoxin A in reducing glabellar line severity (GLS) and to evaluate long-term safety and efficacy following repeated injections. METHODS: In this prospective, randomized, parallel-group, double-blind, multicentre, placebo-controlled Phase III clinical trial, 355 subjects with moderate to severe glabella frown lines received injections of 20 U of letibotulinumtoxin A or placebo. GLS, onset and duration of effect, time to retreatment, and adverse events were evaluated. Response to treatment was defined as a GLS score of 0 or 1 (assessed by the subject and the investigator) and an improvement at Week 4 of ≥2 points in GLS score relative to baseline. RESULTS: At 4 weeks, 78.6% of the active treatment subjects were responders based on the investigator's assessment and 68.8% based on the subject's assessment, resulting in a composite responder rate of 64.7% for the active treatment group, whereas the corresponding rate was 0.0% in the placebo group (P < 0.001). Subjects noted a substantial improvement in GL severity as early as Day 2, with the median time to onset of effect being 3 days. The mean [standard deviation] time until first retreatment for the letibotulinumtoxin A group was 127.26 [65.6] days. Letibotulinumtoxin A was well tolerated. CONCLUSIONS: Letibotulinumtoxin A demonstrates high efficacy and a convincing safety profile in the treatment of glabellar lines.

Efficacy and Safety of a New Resilient Hyaluronic Acid Filler in the Correction of Moderate-to-Severe Dynamic Perioral Rhytides: A 52-Week Prospective, Multicenter, Controlled, Randomized, Evaluator-Blinded Study.

BACKGROUND: The perioral region is highly mobile and subject to multifactorial changes during aging. Resilient Hyaluronic Acid Redensity (RHAR), an RHA filler, was developed with the aim of optimizing outcomes in dynamic facial areas. OBJECTIVE: This randomized, blinded, multicenter clinical study aimed to demonstrate superiority of RHAR over no-treatment control for correction of moderate-to-severe dynamic perioral rhytides. MATERIALS AND METHODS: Blinded live evaluator assessments of efficacy included improvement in perioral rhytides severity using a proprietary scale (Perioral Rhytids Severity Rating Scale [PR-SRS]) and the Global Aesthetic Improvement Scale. Subjects self-assessed their results with FACE-Q, a validated patient-reported outcome measure, and satisfaction scales. Safety was monitored throughout the study based on common treatment responses (CTRs) and adverse events (AEs). RESULTS: The primary efficacy end point was achieved, with the treatment group showing statistically significant superiority over the control group at Week 8 (80.7% vs 7.8% responder rate by PR-SRS, p < .0001). Most patients (66%) were still responders at Week 52 (study completion). Most AEs were CTRs after perioral injection of a dermal filler, and none was a clinically significant treatment-related AE. CONCLUSION: Resilient Hyaluronic Acid Redensity is effective and safe for the correction of dynamic perioral rhytides in all Fitzpatrick phototypes, with marked durability.

High-Dose Neuromodulators: A Roundtable on Making Sense of the Data in Real-World Clinical Practice.

BACKGROUND: For aesthetic treatment with botulinum neurotoxin type A (BoNTA), interest in maximizing treatment duration and efficacy has prompted study of doses higher than those used in registration studies. As data emerge, it is important that physicians understand how to apply study findings to their own practice so that patient demand is satisfied. OBJECTIVES: To bring together leading experts in neuromodulators for a roundtable discussion on the implications of high-dose BoNTA studies for patient care. METHODS: The authors reviewed and discussed recent data from high-dose BoNTA studies for abobotulinum toxin A, incobotulinum toxin A, and Oonobotulinumtoxin A. RESULTS: Discussion focused on the challenges of data interpretation and extrapolation of study findings for real-world patient care. The authors participated in a candid discussion of whether the observed improvements in treatment duration and patient satisfaction warrant treatment with high-dose regimens delivered as high-concentration injections. Safety was also discussed, as well as economic considerations for both practices and patients. Of note, for BoNTA products, the registration dose, when administered in a smaller total volume, appears to give rise to more durable results than those observed in pivotal trials, implicating product concentration as an important consideration. Importantly, at higher doses, extended duration of effect does not appear to be at the expense of natural-looking results. CONCLUSIONS: While the authors provide considerations for the development of individual clinical practice, there is no one-size-fits-all recommendation. It may be that "high-dose" BoNTA is in reality the optimal dose; however, important economic considerations may prevent rapid uptake for all patients.

AbobotulinumtoxinA for the Treatment of Moderate-to-Severe Glabellar Lines: A Randomized, Dose-Escalating, Double-Blind Study.

OBJECTIVE: To evaluate the efficacy and safety of AbobotulinumtoxinA (ABO) dose escalation in the correction of moderate-to-severe glabellar lines. DESIGN: Phase 2, 36-week, multicenter, randomized, dose-ranging, double-blind, placebo-controlled study. METHODS: Adults with moderate-to-severe glabellar lines received a single ABO treatment, dosed at 50, 75, 100, or 125 U, or placebo. Primary endpoint was week 4 composite ≥2-grade responder rate among those achieving a severity score of 0 (none) or 1 (mild) at maximum frown, evaluated using concurrent investigator and subject assessments. Secondary endpoints included ≥1-grade severity improvement, duration of effect, and reporting of treatment-emergent adverse events (TEAEs). RESULTS: Overall, 399 subjects were included (88.2% were female). Week 4 composite ≥2-grade ABO responder rate was 80.0% (50 U), 88.8% (75 U), 90.0% (100 U) and 95.1% (125 U), versus 2.6% with placebo (P<0.001). Responder rate (≥1-grade) ranged between 53% (50 U) and 69% (125 U) at week 24 and between 18% (50 U) and 31% (125 U) at week 36. Median time (weeks) to return to baseline severity/worse, among those scoring 0 (none) or 1 (mild), was 32.3 (50 U), 34.3 (75 U), 36.0 (100 U) and 36.6 (125 U), versus 23.7 (placebo). ABO-related TEAEs were reported in 4% of subjects (80% were mild). No seroconversion to ABO neutralizing antibodies was seen. CONCLUSION: A single ABO treatment provided rapid and effective improvements in glabellar line severity at all doses. Higher doses tended to demonstrate elevated response rates and longer duration of effect. All ABO doses were well-tolerated with low TEAE incidence. J Drugs Dermatol. 2021;20(9):980-987. doi:10.36849/JDD.6263.

Botulinum Toxin Type A for Glabellar Frown Lines: What Impact of Higher Doses on Outcomes?

Botulinum toxin serotype-A (BoNT-A) preparations are widely used to improve the appearance of wrinkles. While effective and well tolerated, patients require retreatment over time to re-establish the effects. There is growing interest from patients as to whether higher doses can prolong response without significantly increasing side effects. We reviewed the efficacy and safety evidence for high-dose BoNT-A treatment of glabellar lines, by evaluating high-dose studies published since 2015. Toxins approved for glabellar line treatment in the US or Europe were considered. "High-dose" indicated doses above the licensed dose for each BoNT-A preparation. Five studies met the inclusion criteria and most were randomized, double-blind trials; designs and population sizes varied. Findings suggested that higher-dose BoNT-A treatment is feasible and may improve response duration without increased safety issues. Around 9 months' median duration was achieved with a 2-2.5-fold increase of the abobotulinumtoxinA on-label dose, or with a 5-fold increase in incobotulinumtoxinA dose. A 2-4-fold increase of the onabotulinumtoxinA on-label dose yielded a median duration of around 6 months. Importantly, patient satisfaction and natural look remained with increasing abobotulinumtoxinA doses. While more data are needed, these findings may lead to more effective, individually tailored treatment plans to meet patient expectations.

The First of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients.

BACKGROUND: PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. OBJECTIVES: The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. METHODS: This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as assessed by the investigator on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment of 20 U prabotulinumtoxinA (4 U/0.1 mL freeze-dried formulation injected into 5 target glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety was evaluated throughout the study. RESULTS: The 352 study patients received a median total dose of 60 U, that is, 3 treatments per year. Fifty-one patients (14.5%) experienced adverse events (AEs) assessed as possibly study drug related; 11.1% experienced study drug-related AEs after the initial treatment. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Six patients (1.7%) experienced study drug-related AEs of special interest: 3 eyelid ptosis (0.9%), 2 speech disorder (0.6%), and 1 blepharospasm (0.3%). Seven patients (2.0%) experienced serious AEs; none were study drug related. Of the 2393 samples tested, 2 patients (0.6%) tested positive for antibotulinum toxin antibodies at a single postbaseline visit. CONCLUSIONS: The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was first established in this early phase II study based on a broad range of outcomes.