Neuronal effects of glabellar botulinum toxin injections using a valenced inhibition task in borderline personality disorder.

Previous studies have indicated that glabellar botulinum toxin (BTX) injections may lead to a sustained alleviation of depression. This may be accomplished by the disruption of a facial feedback loop, which potentially mitigates the experience of negative emotions. Accordingly, glabellar BTX injection can attenuate amygdala activity in response to emotional stimuli. A prototypic condition with an excess of negative emotionality and impulsivity accompanied by elevated amygdala reactivity to emotional stimuli is borderline personality disorder (BPD). In order to improve the understanding of how glabellar BTX may affect the processing of emotional stimuli and impulsivity, we conducted a functional magnetic resonance imaging (fMRI) study. Our hypotheses were (1) glabellar BTX leads to increased activation in prefrontal areas during inhibition performance and (2) BTX decreases amygdala activity during the processing of emotional stimuli in general. Using an emotional go-/no-go paradigm during fMRI, the interference of emotion processing and impulsivity in a sample of n = 45 women with BPD was assessed. Subjects were randomly assigned to BTX treatment or serial acupuncture (ACU) of the head. After 4 weeks, both treatments led to a reduction in the symptoms of BPD. However, BTX treatment was specifically associated with improved inhibition performance and increased activity in the motor cortex. In addition, the processing of negative emotional faces was accompanied by a reduction in right amygdala activity. This study provides the first evidence that glabellar BTX injections may modify central neurobiological and behavioural aspects of BPD. Since the control treatment produced similar clinical effects, these neurobiological findings may be specific to BTX and not a general correlate of symptomatic improvement.

Calcium Hydroxyapatite Filler With Integral Lidocaine CaHA (+) for Soft Tissue Augmentation: Results from an Open-Label Multicenter Clinical Study.

BACKGROUND: Soft tissue augmentation with calcium hydroxylapatite (CaHA) is a versatile technique for line filling, skin tightening, lifting, contouring, and volumizing. The present study was designed to confirm safety and effectiveness of the product with lidocaine (CaHA (+)) in a holistic treatment of nasolabial folds (NLFs), marionette lines, and/or cheeks. METHODS: A total of 207 subjects with moderate to severe facial volume deficit were treated with CaHA(+) in this open-label study. Effectiveness assessments included Merz Aesthetics Scales® (MAS), investigator- and subject-assessed Global Aesthetic Improvement Scales (iGAIS/sGAIS), and FACE-QTM questionnaires. Responder rates were defined as at least one-point improvement on MAS according to blinded rating. Safety was assessed through adverse event reporting. RESULTS: Primary endpoint was evaluated 12 weeks after last injection. Responder rates were 93.6%, 88.7%, and 81.9% in the NLFs, marionette lines, and cheeks, respectively, and were statistically significant above the pre-defined 60% threshold (P< 0.0001). Investigator- and subject-assessed GAIS were consistent and showed high rates of improvement throughout the study, with peak values of 98.0% at week 4 on iGAIS and 93.5% at 12 weeks after last injection on sGAIS. After 18 months, the majority of subjects (52.5%) still perceived improvement via sGAIS. Moreover, total FACE-Q scores demonstrated high subject satisfaction with treatment. All related treatment emergent adverse events were transient and expected injection-site reactions mostly of mild to moderate intensity. CONCLUSION: CaHA (+) has demonstrated safety and effectiveness in the treatment of NLFs, marionette lines, and cheek volume loss in real-life conditions up to 18 months. J Drugs Dermatol. 2022;21(5):481-487. doi:10.36849/JDD.6737.

Clinical effects of glabellar botulinum toxin injections on borderline personality disorder: A randomized controlled trial.

BACKGROUND: Inhibition of frowning via injections of botulinum toxin A (BTX) into the glabellar region has shown beneficial effects in the treatment of major depression. Preliminary research suggests that improvements in the affective domain are not depression-specific, but may also translate to other psychiatric disorders. AIM: This 16-week, single-blind, two-center randomized controlled trial investigated the influence of BTX on clinical symptoms of borderline personality disorder (BPD). METHODS: Fifty-four patients with BPD were randomly assigned to treatment with BTX (n = 27) or a minimal acupuncture (ACU) control condition (n = 27). Clinical outcomes were followed at 2, 4, 6, 8, 12, and 16 weeks. Primary endpoint was the relative score change on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) 8 weeks after baseline relative to the control group and adjusted for treatment center. Secondary and additional outcome variables were self-rated borderline symptoms, comorbid symptoms of depression, psychological distress, and clinical global impression. RESULTS: Participants showed significant improvements at the primary efficacy endpoint in both treatment groups (BTX: M = -0.39, SD = 0.39; ACU: M = -0.35, SD = 0.42), but no superior effect of the BTX condition in comparison with the control intervention was found-F(1,5323) = 0.017, p = 0.68). None of the secondary or additional outcomes yielded significant group differences. Side effects were mild and included headache, transient skin or muscle irritations, and dizziness. CONCLUSION: Evidence regarding the efficacy of BTX for BDP remains limited, and the design of adequate control conditions presents an opportunity for further research.ClinicalTrials.gov registry: Botulinum Toxin A for Emotional Stabilization in Borderline Personality Disorder (BPD), NCT02728778, https://clinicaltrials.gov/ct2/show/NCT02728778.

IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

BACKGROUND: To further explore clinical trial results indicating increasing doses of botulinum toxin A prolong duration of effect, a 2-stage, phase 2, randomized, double-blind study investigated the duration of effect and safety of incobotulinumtoxinA (INCO; Xeomin®, Bocouture®) doses higher than the US Food and Drug Administration-approved 20 units (U) for glabellar frown lines (GFL). The stage 1 primary efficacy and safety results were reported previously. Here, we report the results of the final analysis (stage 1 and 2), including primary and secondary efficacy and safety endpoints. METHODS: A total of 241 subjects with moderate-to-severe GFL were randomized to receive a single treatment with 20 (N=61), 50 (N=60), 75 (N=61), or 100U (N=59) INCO. The primary efficacy endpoint was duration of ≥ 1-point improvement from baseline assessed by investigator at maximum frown on the Facial Wrinkle Scale. RESULTS: The median duration of effect was 175 days for the 20U group (95% CI 142, 185), 185 days for the 50U group (95% CI 182, 205), 210 days for the 75U group (95% CI 182, 217), and 215 days for the 100U group (95% CI 183, 237). The incidence of treatment-related adverse events was low across all doses and there were no treatment-related serious adverse events. CONCLUSIONS: These results demonstrate that all INCO doses were well tolerated, consistent with the known safety profile of 20U, and increasing dose prolongs the duration of effect for GFL. J Drugs Dermatol. 2021;20(10):1052-1060. doi:10.36849/JDD.6377THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Safety of Cohesive Polydensified Matrix Cross-Linked Hyaluronic Acid Volumizing Gel in Temporal Hollows and Cheeks: A Prospective, Open-Label, Postmarket Study.

BACKGROUND: Facial aging is characterized by volume loss and progressive hollowing of temples and cheeks. Biodegradable filler materials are preferred over nonabsorbable materials; of these, hyaluronic acid (HA) fillers are the most often used because of their favorable effectiveness and safety profile. OBJECTIVE: To confirm the safety and effectiveness of Cohesive Polydensified Matrix (CPM)-HA26 gel in the treatment of volume deficiency. METHODS: Subjects received up to 2 treatments in the temples and/or cheeks. A blinded investigator assessed improvement according to the Merz Temple Volume Scale (MTVS) and Merz Cheek Fullness Assessment Scale (MCFAS). Subjects were followed for 48 weeks after the last treatment. RESULTS: In total, 87 healthy subjects were enrolled. The proportion of subjects achieving at least a 1-grade improvement on MTVS and/or MCFAS was above 70% for each (MTVS: Weeks 4, 24, and 48 = 95.4%, 94.2%, and 77.0%; MCFAS: Weeks 4, 24, and 48 = 92.3%, 83.1%, and 71.8%). Based on MTVS and MCFAS scores at Visit 5, improvement remained visible at up to 48 weeks. No treatment-related serious AEs occurred. CONCLUSION: CPM-HA26 demonstrated both a favorable safety and effectiveness profile, with improvement in facial volume evident for up to 48 weeks. It was well tolerated and had a positive, long-lasting effect.

Repetitive Daylight Photodynamic Therapy versus Cryosurgery for Prevention of Actinic Keratoses in Photodamaged Facial Skin: A Prospective, Randomized Controlled Multicentre Two-armed Study.

Actinic keratoses are a chronic condition in ultraviolet-damaged skin, with a risk of progressing to invasive skin cancer. The aim of this study was to investigate the preventive potential of field-directed repetitive daylight photodynamic therapy for actinic keratoses. A randomized trial was performed, including 58 patients with ≥5 actinic keratoses on photodamaged facial skin, who received either 5 full-face sessions of daylight photodynamic therapy within a period of 2 years or lesion-directed cryosurgery. Primary outcome was the mean cumulative number of new actinic keratoses developed between visits 2 and 6 (visit 6 being a follow-up). This outcome was lower after daylight photo-dynamic therapy (7.7) compared with cryosurgery (10.2), but the difference did not reach significance (-2.5, 95% confidence interval -6.2 to 1.2; p=0.18). Several signs of photoageing (fine lines, pigmentation, roughness, erythema, sebaceous gland hyperplasia) were significantly reduced after daylight photodynamic therapy, but not after cryosurgery. Significantly less pain and fewer side-effects were reported during daylight photodynamic therapy than during cryosurgery. This study found that repetitive daylight photodynamic therapy had photo-rejuvenating effects. However, the prevention of actinic keratoses by this therapy could not be proven in a statistically reliable manner.

Facial Skin Revitalization with Cohesive Polydensified Matrix-HA20G: Results from a Randomized Multicenter Clinical Study.

BACKGROUND: There is a growing interest in the application of hyaluronic acid (HA) derivatives in skin quality improvement. The aim of this study was to confirm safety and effectiveness of cohesive polydensified matrix-hyaluronic acid + glycerol (CPM-HA20G; Belotero Revive) in revitalization of early-onset photodamaged facial skin. METHODS: A total of 159 subjects with early signs of facial photodamaged skin were randomized in a 2:1 ratio to multiple- or single-dose treatment with CPMHA20G. Effectiveness assessments included biophysical measurements of skin hydration; elasticity, firmness, and roughness; investigator- and subject-assessed Global Aesthetic Improvement Scales; and FACE-Q Skin Changes and Treatment Satisfaction questionnaires. RESULTS: In both treatment groups, skin hydration improved from baseline to all follow-up visits in subjects with dry or very dry skin. This improvement was significant at week 16 after initial treatment in the multiple-dose group (P = 0.0013). Investigator- and subject-reported outcomes showed that the majority of subjects across all skin hydration types benefited from treatment, with higher satisfaction rates observed in the multiple-dose group. According to investigator-assessed Global Aesthetic Improvement Scale, 90.7% of subjects at week 12 in the multiple-dose and 74.6% of subjects at week 4 in the single-dose group were rated as at least "improved." All related treatment-emergent adverse events were transient, expected injection-site reactions of mild to moderate intensity. CONCLUSIONS: Effectiveness of CPM-HA20G for skin hydration in subjects with dry or very dry skin was demonstrated up to 9 months after last injection. Overall, CPM-HA20G demonstrated effective and safe use in facial skin revitalization among subjects with early-onset photodamaged skin.

IncobotulinumtoxinA Demonstrates Safety and Prolonged Duration of Effect in a Dose-Ranging Study for Glabellar Lines.

BACKGROUND: Recently reported clinical data provides evidence that increasing the dose of botulinum toxin A increases the duration of efficacy. A 2-stage Phase 2, randomized, double-blind study investigated the duration of effect and safety of IncobotulinumtoxinA (INCO; Xeomin®, Bocouture®; Merz Pharmaceuticals GmbH, Frankfurt am Main, Germany) at doses higher than the approved 20 units (U) for glabellar frown lines (GFL). Primary safety and efficacy endpoints of Stage 1 are reported here. METHODS: 151 subjects with moderate-to-severe GFL were randomized 1:2:2 to receive a single treatment with 20U, 50U, or 75U INCO. The primary efficacy endpoint was median duration of at least 1-point improvement from baseline as assessed by investigator at maximum frown on the Facial Wrinkle Scale. RESULTS: The median duration of effect was 185 days for the 50U dose group (95% CI:[182, 205]) and 210 days for the 75U dose group (95% CI:[182, 217]). Duration of effect was significantly longer for 75U vs 50U (P=0.0400) and 20U (P=0.0166) despite the study not being powered for confirmatory statistical significance testing between the dose groups. Duration of effect was also longer for 50U vs 20U, however; statistical significance was not reached (P=0.4349). The incidence of treatment-related adverse events was low across all doses (20U:2[6.7%], 50U:6[10.0%] and 75U:8[13.1%]). CONCLUSIONS: These results demonstrate a dose effect of at least 6 months duration with higher doses in the majority of GFL subjects. All doses were well tolerated and safety was consistent with the known safety profile of 20U INCO for GFL. J Drugs Dermatol. 2020;19(10):985-991. doi:10.36849/JDD.2020.5454.

Safety and Performance of Etermis 3 and 4 in Wrinkles/Folds Treatment and Facial Volume Enhancement: A Prospective, Evaluator-Blinded, Open-Label Study.

BACKGROUND: Facial aging is characterized by increased prominence of nasolabial folds (NLFs), marionette lines, and thinning of the lips. Cross-linked hyaluronic acid injection is a very effective method for the temporary correction of these areas. OBJECTIVE: To confirm the clinical performance and the safety of Etermis 3 (ET3) and/or Etermis 4 (ET4) in the treatment of moderate and severe wrinkles/folds, as well as lip volume enhancement. METHODS: Subjects were treated in at least two facial areas (NLFs, marionette lines, lips). ET3 was used in facial moderate wrinkles while ET4 was used in severe facial skin volume loss. An optional touch-up 1 month after treatment was possible. A blinded investigator assessed improvement on Merz Aesthetic Scales (MAS). Subjects were followed-up for 12 months after the last treatment. RESULTS: In total, 154 healthy subjects were enrolled. The proportion of subjects achieving ≥1 score improvement in MAS after treatment was above 60% for ET4 (Month 6/7: NLFs 94.9% and marionette lines 81.4%, p≤0.0004; Month 3/4: lips 63.0%, p=0.39) and ET3 (Month 6/7: marionette lines 79.4%, p=0.0005; Month 3/4: lips 65.5%, p=0.31). Facial improvement was still visible at Month 12/13 for ET4 (NLFs ≥76.6%, marionette lines ≥61%, lips ≥36%) and ET3 (marionette lines ≥50% and lips ≥21.9%). No treatment-related serious AEs occurred. The most frequent AEs were injection-site reactions. CONCLUSION: Etermis 3 and Etermis 4 demonstrated good clinical performance and safety for NLFs and marionette lines volume enhancement for up to 12 months. Both products can also be used safely to treat lips for volume augmentation.

Safety, Tolerability, and Efficacy of Repeat-Dose Injections of IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results from a Prospective, Open-Label, Phase III Study.

In aesthetic practice, wrinkles in the upper face are commonly treated with repeat-dose injections. The objective of this study was to investigate the safety, tolerability, and efficacy of repeat-dose injections of incobotulinumtoxinA in the combined treatment of moder-ate to severe upper facial lines (UFL) [glabellar frown lines (GFL), horizontal forehead lines (HFL), and lateral periorbital lines (LPL)]. Healthy subjects (≥18 years) with moderate to severe GFL, HFL, and LPL on the Merz Aesthetics Scales (MAS) at maximum contrac-tion were administered 54 to 64 U of incobotulinumtoxinA (GFL, 20 U; HFL, 10 to 20 U; LPL, 24 U) in up to four, 120-day treatment cycles. Adverse events (AE) were recorded for each cycle until 120 ± 7 days after treatment. Investigator-assessed MAS scores were evaluated for each treated area at maximum contraction on day 30 [responder = score of “none” (0) or “mild” (1)]. Subject-assessed scores for overall appearance of the upper face of “much improved” or “very much improved” were noted at day 30 of each treatment cycle on the Global Impression of Change Scale (GICS). Overall, 140 subjects were treated, and 125 subjects completed the study. Mean injected units per injection cycle ranged from 56.3 U to 57.7 U. During the four-cycle study period 17.1% of total treated subjects experienced a treatment emergent adverse event (TEAE). TEAEs of special interest were documented for 9 subjects (6.4%), in 6 of these subjects (4.3%) the TEAEs were related to treatment. No clinically significant mean changes in laboratory and vital-sign values were observed from screening to final-treatment visit. Over the study interval, a response rate of > 80% on the investigator-assessed MAS was reported for all treated areas except HFL. Greater than 80% of subjects in cycles 1, 3, and 4 and 78.5% of subjects in cycle 2 reported ratings of “much improved” or “very much improved” on the GICS for the overall appearance of the upper face. Incobotu-linumtoxinA for the repeat-dose treatment of UFL is safe and well tolerated with a stable safety profile, without new formation of neutralizing antibodies and has excellent efficacy during prolonged administration. J Drugs Dermatol. 2020;19(5):461-469. doi:10.36849/JDD.2020.5013.

Managing intravascular complications following treatment with calcium hydroxylapatite: An expert consensus.

BACKGROUND: Inadvertent intra-arterial injection of dermal fillers including calcium hydroxylapatite (CaHA) can result in serious adverse events including soft tissue necrosis, permanent scarring, visual impairment, and blindness. When intra-arterial injection occurs, immediate action is required for optimal outcomes, but the infrequency of this event means that many physicians may never have experienced this scenario. The aim of this document is to provide evidence-based and expert opinion recommendations for the recognition and management of vascular compromise following inadvertent injection of CaHA. METHODS: An international group of experts with experience in injection of CaHA and management of vascular complications was convened to develop a consensus on the optimal management of vascular compromise following intra-arterial CaHA injection. The consensus members were asked to provide preventative advice for the avoidance of intravascular injection and to produce a treatment protocol for acute and delayed presentation. To ensure all relevant treatment options were included, the recommendations were supplemented with a PubMed search of the literature. RESULTS: For prevention of intra-arterial CaHA injection, consensus members outlined the importance of a thorough knowledge of facial vascular anatomy and patient history, as well as highlighting potential risk zones and optimal injection techniques. Individual sections document how to recognize the symptoms of vascular occlusion leading to vision loss and tissue necrosis as well as detailed treatment protocols for the management of these events. For impending tissue necrosis, recommendations are provided for early and delayed presentations with treatment protocols for acute and follow-up treatment. A separate section details the treatment options for open and closed wounds. CONCLUSIONS: All physicians should be prepared for the eventuality of intra-arterial injection of a dermal filler, despite its rarity. These consensus recommendations combine advice from aesthetic experts with the latest reports from the published literature to provide an up-to-date office-based protocol for the prevention and treatment of complications arising from intra-arterial CaHA injection.

Effectiveness and Safety of an Overnight Patch Containing Allium cepa Extract and Allantoin for Post-Dermatologic Surgery Scars.

BACKGROUND: An occlusive overnight intensive patch medical device (OIP) containing onion extract and allantoin has been developed for preventing and treating dermatologic scars and keloids. Here, we examined the efficacy and safety of the OIP for post-dermatologic surgery scars. METHODS: This was an intra-individual randomized, observer-blind, controlled study in adults with post-dermatologic surgery scars. Two scars per subject were randomized to no treatment or overnight treatment with the OIP for 12-24 weeks. Scar quality was assessed using the Patient and Observer Scar Assessment Scale (POSAS) and a Global Aesthetic Improvement Scale. RESULTS: A total of 125 subjects were included. The decrease in observer-assessed POSAS from baseline was significantly greater for treated than untreated scars at week 6 (p < 0.001) and 24 (p = 0.001). The decrease in patient-assessed POSAS was significantly greater for the treated scar than the untreated scar at week 12 (p = 0.017) and 24 (p = 0.014). Subject- and investigator-evaluated Global Aesthetic Improvement Scale scores were higher for the treated than the untreated scar at all visits. All subjects considered the global comfort of the OIP to be good or very good, and no safety concerns were identified. CONCLUSIONS: This study confirmed that the OIP safely promotes scar healing after minor dermatologic surgery. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The Use of a Self-Occluding Topical Anasthetic in Daily Practice: A Non-Interventional Study.

INTRODUCTION: A variety of topical anesthetic creams are available to reduce pain associated with dermatological procedures. Pliaglis is a self-occluding eutectic mixture of lidocaine and tetracaine. STUDY OBJECTIVES: To evaluate the post-marketing safety profile of Pliaglis and efficacy in terms of pain reduction, product satisfaction, and daily practice use prior to pre-defined dermatological procedures. METHODS: A prospective, non-interventional study conducted at 44 sites in four European countries; 581 patients were treated prior to dermatological procedures such as pulsed-dye laser therapy, laser-assisted hair removal, non-ablative laser resurfacing, dermal filler injections, and vascular access. Efficacy was assessed by patients and investigators and included pain intensity (visual analogue scale [VAS]), satisfaction, and adequacy of pain relief. Safety was evaluated by adverse event (AE) reporting. RESULTS: In 75% of the performed procedures, patients scored the pain experienced during the procedure as ≤30 mm on the VAS and most were very satisfied or satisfied with the pain reduction. The investigators assessed the product as providing adequate anesthesia in 97% of the performed procedures and were mostly very satisfied or satisfied with the convenience of use (79%) and tolerability (95%). Twenty-four AEs were reported in 18 (3%) patients. DISCUSSION: Most patients experienced mild pain only as evident by the ≤ 30 mm VAS scores. Patients and investigators were aligned with regards to both product satisfaction and their opinion on adequacy of pain reduction. The AE frequency was low compared to previous studies, possibly relating to different ways of collecting AEs. CONCLUSION: Pliaglis was well-tolerated and provided adequate pain reduction prior to dermatological procedures. www.clinicaltrials.gov (NCT01800474).

J Drugs Dermatol. 2018;17(4):413-418.

Partial study data have been presented at the Anti-Aging Medicine European Congress (AMEC), Paris; October, 24-25, 2014, and the European Academy of Dermatology and Venereology (EADV), Istanbul; October 2-6, 2013.

Patient-Reported Outcomes following Split-Face Injection of 2 Volumizing Fillers in the Upper Cheeks.

BACKGROUND: Patient-reported outcomes are important measures when assessing the efficacy of aesthetic procedures. OBJECTIVE: To compare outcomes between 2 volumizing hyaluronic acid fillers. MATERIALS AND METHODS: Subjects with moderate-to-severe volume loss in the cheeks were randomized in a split-face design to malar enhancement with Cohesive Polydensified Matrix 26 mg/ml HA (CPM-26) and Vycross 20 mg/ml HA (VYC-20). The same injection technique and injection volume were applied for both sides of the face. Anesthetics, overcorrection, and touch-ups were not permitted. Blinded subjects assessed aesthetic improvements using the Global Aesthetic Improvement Scale and treatment satisfaction by confirming their willingness to repeat treatment or recommend it to friends. Follow-up was 18 months. RESULTS: A total of 45 subjects received a single 2 mL injection of CPM-26 on one side and VYC-20 on the contralateral side of the face. The proportion of subjects reporting improvement on the Global Aesthetic Improvement Scale compared with baseline for CPM-26 and VYC-20 was 97.7% and 88.6%, respectively, at 3 months, 73.8% and 71.1% at 12 months, and 61.0% and 56.7% at 18 months. Treatment satisfaction was high, with the majority of subjects stating that they would repeat treatment and recommend it to friends, but at each time point, a higher proportion of subjects was more satisfied with the CPM-26-treated side of the face. CONCLUSIONS: In this first direct comparison of CPM-26 and VYC-20, the majority of subjects were satisfied with both treatments throughout the study. Patient-reported outcome measures identified a trend in favor of CPM-26.

Effectiveness evaluation of two volumizing hyaluronic acid dermal fillers in a controlled, randomized, double-blind, split-face clinical study.

BACKGROUND: Enhancement of the midface can be achieved with volumizing hyaluronic acid (HA) fillers. OBJECTIVE: The objective of this study was to compare the safety and effectiveness of Cohesive Polydensified Matrix® 26 mg/mL HA gel (CPM-26) and Vycross® 20 mg/ml HA gel (VYC-20) in a controlled, randomized, evaluator-blind, split-face clinical study. PATIENTS AND METHODS: Subjects with moderate-to-severe malar volume loss on the Merz Aesthetics Scale (MAS) received CPM-26 on one side and VYC-20 on the contralateral side of the face. Effectiveness assessments were performed by blinded evaluators including photographic and live MAS ratings and live Global Aesthetic Improvement Scale (GAIS) ratings. Calculations of anatomical volume variations at month 3 (M3), month 6 (M6), month 12 (M12) and month 18 (M18) were also performed. RESULTS: Non-inferiority of CPM-26 versus VYC-20 was demonstrated at M3 (primary end point) based on MAS. GAIS rating showed that significantly more subjects had better improvement with CPM-26 than with VYC-20 at month 1, M3, M12 and M18 (p=0.0032, p=0.0074, p=0.0384 and p=0.0110, respectively). Standardized evaluation of volume variations from baseline to M3, M12 and M18 showed that CPM-26 created more volume augmentation at all time points, and the difference was significant at M3. CONCLUSION: CPM-26 was non-inferior to VYC-20 based on MAS ratings at M3 and demonstrated a favorable safety and effectiveness profile for midfacial volume enhancement with results lasting up to M18.

IncobotulinumtoxinA for Aesthetic Indications: A Systematic Review of Prospective Comparative Trials.

BACKGROUND: IncobotulinumtoxinA is a botulinum toxin type A (BoNTA) indicated for temporary improvement in the appearance of upper facial lines with well-established efficacy and safety profiles. Whether incobotulinumtoxinA and other BoNTAs are equipotent is subject of debate. OBJECTIVE: To compare the efficacy of incobotulinumtoxinA and other BoNTAs for aesthetic applications. MATERIALS AND METHODS: PubMed and Embase were systematically searched for prospective clinical trials comparing incobotulinumtoxinA with onabotulinumtoxinA, abobotulinumtoxinA, or placebo for aesthetic applications. RESULTS: Fifteen articles met the selection criteria. Two studies found that incobotulinumtoxinA was noninferior or equivalent to onabotulinumtoxinA for the treatment of glabellar frown lines (GFLs). Eight studies found no difference in efficacy between incobotulinumtoxinA and other BoNTAs. One study suggested differences in response rates at certain time points between incobotulinumtoxinA and onabotulinumtoxinA for GFLs, and one suggested differences for dynamic horizontal forehead lines but not for GFLs or lateral periorbital lines, but both had study design issues limiting the ability to draw conclusions. Finally, 3 placebo-controlled studies demonstrated the efficacy of incobotulinumtoxinA for treating GFLs and upper facial lines. CONCLUSION: The weight of the evidence from comparative clinical trials indicates that incobotulinumtoxinA, onabotulinumtoxinA, and abobotulinumtoxinA have similar efficacy for aesthetic applications.

Mid-Face Volumization With Hyaluronic Acid: Injection Technique and Safety Aspects from a Controlled, Randomized, Double-Blind Clinical Study.

BACKGROUND: Injection of hyaluronic acid (HA) volumizing fillers in the malar area is intended for rejuvenation of the mid-face. The choice of products, depth, and technique of injection depends on the desired level of volume enhancement and practitioners' preferences.

OBJECTIVE: To describe a volumizing injection technique in the scope of a controlled, randomized, double-blind, single-center, split-face clinical study. MATERIALS & METHODS: A total of 45 subjects with bilateral symmetrical moderate to severe volume loss in the malar area received a single 2 mL injection of CPM®-26 (Cohesive Polydensified Matrix®) on one side and VYC®-20 (VYCROSS®) on the contralateral side of the face. The same injection technique was applied for both sides of the face. Use of anesthetics, overcorrection, and touch-ups were not permitted. The investigator completed a product satisfaction questionnaire. Adverse events (AE) and injection-site reactions (ISRs) were reported during the study.

RESULTS: The products were placed at the epiperiosteal depth in 88.9% (n=40), at the subdermal depth in 8.9% (n=4) and at both levels in 2.2% (n=1) of subjects. Fanning technique using cannulae was applied in most cases (97.8%, n=44). Results of the investigator satisfaction questionnaire allowed to characterize CPM-26 in comparison to other volumizing gels. Both study products were generally well tolerated. Local reactions were transient and of mild to moderate intensity, with the most frequent ones being redness, pain, and swelling.

CONCLUSION: Adequate injection technique in volumizing treatments is essential to create a natural aesthetic rejuvenation while respecting the safety aspect of the procedures. A 22G blunt cannula used with CPM-26 was preferred due to an easier and a more homogeneous distribution of the product. The investigator also appreciated CPM-26 for its ease of injection, positioning, lifting, and volumizing capacity.

J Drugs Dermatol. 2017;16(4):351-357.

Hyaluronic acid fillers with cohesive polydensified matrix for soft-tissue augmentation and rejuvenation: a literature review.

BACKGROUND: Cohesive monophasic polydensified fillers show unique viscoelastic properties and variable density of hyaluronic acid, allowing for a homogeneous tissue integration and distribution of the material. OBJECTIVE: The aim of this paper was to review the clinical data regarding the performance, tolerability, and safety of the Belotero(®) fillers for soft-tissue augmentation and rejuvenation. METHODS: A literature search was performed up until May 31, 2015 to identify all relevant articles on Belotero(®) fillers (Basic/Balance, Hydro, Soft, Intense, Volume) and equivalent products (Esthélis(®), Mesolis(®), Fortélis(®), Modélis(®)). RESULTS: This comprehensive review included 26 papers. Findings from three randomized controlled trials showed a greater reduction in nasolabial fold severity with Belotero(®) Basic/Balance than with collagen (at 8, 12, 16, and 24 weeks, n=118) and Restylane(®) (at 4 weeks, n=40), and higher patient satisfaction with Belotero(®) Intense than with Perlane(®) (at 2 weeks, n=20). With Belotero(®) Basic/Balance, an improvement of at least 1 point on the severity scale can be expected in ~80% of patients 1-6 months after injection, with an effect still visible at 8-12 months. Positive findings were also reported with Belotero(®) Volume (no reduction in hyaluronic acid volume at 12 months, as demonstrated by magnetic resonance imaging), Soft (improvement in the esthetic outcomes when used in a sequential approach), and Hydro (improvement in skin appearance in all patients). The most common adverse effects were mild-to-moderate erythema, edema, and hematoma, most of which were temporary. There were no reports of Tyndall effect, nodules, granulomas, or tissue necrosis. CONCLUSION: Clinical evidence indicates sustainable esthetic effects, good safety profile, and long-term tolerability of the Belotero(®) fillers, particularly Belotero(®) Basic/Balance and Intense.

Efficacy and Safety of IncobotulinumtoxinA in the Treatment of Upper Facial Lines: Results From a Randomized, Double-Blind, Placebo-Controlled, Phase III Study.

BACKGROUND: Treating upper facial lines (UFL)-a combination of glabellar frown lines (GFL), horizontal forehead lines (HFL), and lateral periorbital lines (LPL)-is a common aesthetic practice. OBJECTIVE: To provide the first placebo-controlled evidence of the efficacy and safety of incobotulinumtoxinA for UFL. METHODS: Healthy subjects (≥18 years) with moderate-to-severe GFL, HFL, and LPL on the Merz Aesthetics Scales (MAS) at maximum contraction were randomized to incobotulinumtoxinA or placebo. For incobotulinumtoxinA, 54 to 64 U were administered (GFL, 20 U; HFL, 10-20 U; LPL, 24 U). Investigator-assessed MAS scores were evaluated for each area at maximum contraction on Day 30, both separately (responder = score of "none" [0] or "mild" [1]) and combined (UFL; sum score ≤3). Adverse events were recorded until 120 ± 7 days after treatment. RESULTS: Overall, 156 subjects were treated (incobotulinumtoxinA: 105; placebo: 51). On Day 30 at maximum contraction, a significant (p ≤ .0001) effect of incobotulinumtoxinA versus placebo for GFL (84.5% vs 0.0%, respectively), HFL (70.9% vs 2.1%), LPL (64.1% vs 2.1%), and UFL combination (55.3% vs 0.0%) was demonstrated for investigator-assessed "none" or "mild" scores. Two cases of mild eyelid ptosis occurred with incobotulinumtoxinA. CONCLUSION: IncobotulinumtoxinA demonstrated significant efficacy in treating GFL, HFL, and LPL separately and combined, as well as a good safety profile.

A prospective, comparative survey to investigate practitioners' satisfaction with a cohesive, polydensified-matrix(®) , hyaluronic acid-based filler gel with and without lidocaine for the treatment of facial wrinkles.

BACKGROUND: Lidocaine-containing dermal fillers may reduce procedural pain compared with lidocaine-free counterparts. OBJECTIVES: To assess practitioners' administration experience with, and the efficacy and safety of, a cohesive, polydensified-matrix(®) , hyaluronic acid-based filler containing lidocaine vs. its lidocaine-free counterpart. METHODS: The lidocaine-containing formulation was injected to one side of the face and the lidocaine-free to the other in 29 females (30-85 years). Administered dose was appropriate to the treatment zone and technique varied according to zone and practitioner preference. Questionnaires assessed practitioners' administration experience, their perception of results, subject satisfaction, and product safety. RESULTS: Practitioners considered the formulations to be similar in terms of ejection force, texture, and placement. The blanching technique was used for 72% of subjects, and its ease was rated as "identical" for both products in 81% of applications and "easier" for the lidocaine-containing product in 6.9% of applications. Results with both formulations were "identical" for 86% of applications and "similar" for the remainder. In 86% of cases, practitioners would "certainly" consider continuing treatment with the lidocaine-containing formulation. All subjects were "satisfied" with treatment. Practitioners reported that, compared with the lidocaine-free product, subject-assessed pain with the lidocaine-containing product was "less prominent" for 86% and 79% of participants during and following treatment, respectively. Similarly, mean pain intensity was significantly lower for the lidocaine-containing preparation (P = 0.0001). Adverse events were similar for both treatments. CONCLUSIONS: The lidocaine-containing dermal filler significantly reduced pain during and following treatment compared with the same preparation without lidocaine, without impact on administration, aesthetic outcome, or safety.