PrabotulinumtoxinA vs OnabotulinumtoxinA for the Treatment of Adult Males With Moderate to Severe Glabellar Lines: Post-hoc Analyses of the Phase III Clinical Study Data.

BACKGROUND: Despite a growing interest among men in cosmetic procedures such as botulinum toxin, comparator clinical trial data in this population are limited. OBJECTIVES: The authors sought to compare the efficacy and safety of prabotulinumtoxinA and onabotulinumtoxinA for the treatment of males with moderate to severe glabellar lines. METHODS: Post-hoc analyses were performed on the subpopulation of male patients treated with either a single dose of 20 U prabotulinumtoxinA (n = 25) or 20 U onabotulinumtoxinA (n = 31) in the EVB-003 Phase III glabellar line clinical study. One key efficacy endpoint was the proportion of responders with a ≥1-point improvement from baseline at maximum frown on the 4-point Glabellar Line Scale. RESULTS: Compared with onabotulinumtoxinA-treated males, the percentages of responders who had a ≥1-point improvement on the Glabellar Line Scale at maximum frown were higher at all postbaseline time points for prabotulinumtoxinA-treated males (P > 0.05 at all visits) by an absolute overall mean difference of 10.1% across all visits. Similar trends were observed for efficacy endpoints based on global aesthetic improvement and subject satisfaction. PrabotulinumtoxinA-treated males had a higher incidence of treatment-related headache and eyelid ptosis. CONCLUSIONS: The percentages of patients who met the definition of a responder were higher at almost all time points examined for prabotulinumtoxinA-treated males. Despite the high level of consistency across all measures, differences between the 2 treatment groups did not reach statistical significance. Further study is warranted to establish if these post-hoc analyses observations are reproducible in a larger male patient population.

Significantly Increased Patient Satisfaction Following Liquid Formulation AbobotulinumtoxinA Treatment in Glabellar Lines: FACE-Q Outcomes From a Phase 3 Clinical Trial.

BACKGROUND: The FACE-Q patient-reported outcome assesses patient experiences/outcomes with aesthetic facial procedure. A recent trial of abobotulinumtoxinA (ASI, liquid formulation) was the first to our knowledge to assess satisfaction with FACE-Q after glabellar line (GL) injection. OBJECTIVES: The authors sought to evaluate patient satisfaction with ASI for GL treatment employing 3 FACE-Q scales: facial appearance, psychological well-being, and aging appearance. METHODS: This was a Phase 3, randomized, double-blind, placebo-controlled trial (NCT02353871) of ASI 50 units in adults with moderate-to-severe GL with 6-month follow-up. RESULTS: Significantly greater least squares mean changes from baseline were associated with ASI treatment (N = 125) vs placebo (N = 59) for satisfaction with facial appearance at all visits until day 148 (5 months; P < 0.0001-0.0037), psychological well-being at all visits (P < 0.0001-0.0279), and aging appearance at all visits except day 148 (P < 0.0001-0.0409). Significant differences (ASI vs placebo) were observed at all visits for individual items: "how rested your face looks" (P < 0.0001-0.0415), "I feel okay about myself" (P = 0.0011-0.0399), and "I feel attractive" (P < 0.0001-0.0102). Maximal least squares mean (standard error) changes in aging appearance score were -1.4 (0.3; ASI) and -0.3 (0.4; placebo). Investigators' live assessment of GL at maximum frown significantly correlated with improvements in FACE-Q facial appearance and psychological scales (all patients: r = -0.41 and r = -0.36 [both P < 0.0001], respectively). CONCLUSIONS: Significant improvements in patient satisfaction with aging, facial appearance, and, importantly, psychological well-being were demonstrated with ASI employing FACE-Q scales up to 5 to 6 months post-injection. Results support a long duration of efficacy with ASI and use of FACE-Q in future trials and clinical practice.

Liquid Formulation of AbobotulinumtoxinA: A 6-Month, Phase 3, Double-Blind, Randomized, Placebo-Controlled Study of a Single Treatment, Ready-to-Use Toxin for Moderate-to-Severe Glabellar Lines.

BACKGROUND: Safety and efficacy of botulinum toxin A for glabellar line (GL) treatment are well established. Currently approved formulations require reconstitution before injection. OBJECTIVES: The authors sought to assess 6-month efficacy, safety, and patient satisfaction of new ready-to-use abobotulinumtoxinA solution for injection (ASI) in patients with moderate-to-severe GL at maximum frown. METHODS: The authors conducted a phase 3, double-blind, randomized, placebo-controlled trial (NCT02353871). Patients (N = 185) were randomized (2:1) to receive ASI 50 U or placebo. GL severity was evaluated at days 8, 15, 29, 57, 85, 113, 148, and 183 employing a 4-point scale for investigator's live assessment (ILA) and subject's self-assessment (SSA). Primary endpoint was ILA of GL at maximum frown at day 29, and secondary endpoints were ILA and SSA of GL at maximum frown (all time points), patient satisfaction with GL appearance, time to onset, and duration of action. RESULTS: Responder rates were significantly higher for ASI vs placebo (88.3% vs 1.4%; P < 0.0001) at day 29 by ILA and all time points by ILA (P < 0.0001-0.0441) and SSA (P < 0.0001-0.0036). Sixty percent of patients reported onset of treatment response on or before day 3 (P < 0.0001 vs placebo), and in 5% of patients, efficacy by ILA lasted 6 months (day 183; P = 0.0441 vs placebo). Patient satisfaction rates were significantly higher for ASI vs placebo at all visits (P < 0.0001). Safety was comparable with the known abobotulinumtoxinA profile. CONCLUSIONS: ASI was significantly efficacious for improving moderate or severe GL vs placebo by investigator and patient assessment. ASI was associated with high patient satisfaction, a long duration of action, and comparable safety profile to abobotulinumtoxinA.

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Phase III, Non-Inferiority Study Comparing PrabotulinumtoxinA and OnabotulinumtoxinA 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 efficacy and safety of prabotulinumtoxinA compared to onabotulinumtoxinA and placebo for the treatment of glabellar lines. METHODS: This was a 150-day, multicenter, double-blind, controlled, single-dose Phase III study. Adult patients (n = 540) with moderate to severe glabellar lines at maximum frown as assessed by the investigator on the validated 4-point Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), who also felt that their glabellar lines had an important psychological impact, were enrolled. Patients were randomized 5:5:1 to receive a single treatment (0.1 mL injected into each of 5 glabellar sites) of 20 U prabotulinumtoxinA (n = 245), 20 U onabotulinumtoxinA (n = 246), or placebo (n = 49). The primary efficacy endpoint was the proportion of responders (patients with a Glabellar Line Scale score of 0 or 1 at maximum frown by investigator assessment) on day 30. RESULTS: Responder rates for the primary efficacy endpoint were 87.2%, 82.8%, and 4.2% in the prabotulinumtoxinA, onabotulinumtoxinA, and placebo groups, respectively. The absolute difference between prabotulinumtoxinA and onabotulinumtoxinA groups was 4.4% (95% confidence interval [-1.9, 10.8]). Given that the lower bound of the 95% confidence interval for the difference was less than -10.0%, noninferiority of prabotulinumtoxinA vs onabotulinumtoxinA was concluded. Five patients (3 prabotulinumtoxinA, 1.2%; 1 onabotulinumtoxinA, 0.4%; 1 placebo, 2.0%) experienced serious adverse events, none of which were study drug related. CONCLUSIONS: A single treatment of 20 U prabotulinumtoxinA was safe and effective and noninferior to 20 U onabotulinumtoxinA for the treatment of moderate to severe glabellar lines.

Update of the S1 guidelines on the definition and treatment of primary hyperhidrosis.

Focal hyperhidrosis can have a considerable impact on social and occupational activities and be associated with significant impairment in quality of life. Primary (idiopathic) hyperhidrosis is neither caused by systemic disorders nor by external factors. It usually occurs in areas characterized by a high density of sweat glands such as the axillae and hands. The diagnosis of focal hyperhidrosis is based on history and clinical findings. Supplementary diagnostic tests include gravimetry (measurement of the amount of sweat) and the iodine starch test (which shows the area of sweating). Treatment options consist of topical agents, botulinum toxin A injections, iontophoresis, treatment with radiofrequency, microwaves, or ultrasound as well as surgical procedures (axillary suction curettage, sympathectomy). Systemic agents such as anticholinergics may also be used. Selection of the most appropriate therapeutic approach depends on the site affected, prior treatment as well as the patient's requests.

Liquid Formulation of AbobotulinumtoxinA Exhibits a Favorable Efficacy and Safety Profile in Moderate to Severe Glabellar Lines: A Randomized, Double-Blind, Placebo- and Active Comparator-Controlled Trial.

BACKGROUND: In most countries, approved botulinum toxin type A formulations require reconstitution before injection. OBJECTIVES: To evaluate the efficacy and safety of a ready-to-use liquid formulation of abobotulinumtoxinA (abobotulinumtoxinA solution for injection, ASI) in subjects with moderate to severe glabellar lines (GL). METHODS: In this Phase II, double-blind, placebo-controlled, randomized study, 176 female subjects (aged 30 to 60 years) were randomized into five treatment groups: ASI 20, 50, or 75 U, reconstituted abobotulinumtoxinA (aboBoNT-A) 50 U, and placebo. GL severity was assessed at maximum frown using a 4-point grading scale. Responders were subjects with severity grade of moderate [2] or severe [3] at baseline improving to none [0] or mild [1], evaluated at each time-point by Investigator's Live Assessment (ILA) or Subject's Self-Assessment (SSA). Safety profiles were also determined. RESULTS: Baseline characteristics were similar across groups. Responder rates on Day 29 by ILA were significantly greater for ASI 20, 50, and 75 U versus placebo (88.9%, 91.4%, and 87.9% vs. 0%, respectively; P < 0.0001). Similar results were observed by SSA. A greater proportion of responders was observed in ASI groups vs placebo from Day 8 to 113 for ILA and SSA (P < 0.001). AboBoNT-A responder rate on Day 29 for ILA was 77.1% (P < 0.1006 vs ASI 50 U); with comparable results by SSA. The ASI safety profile was comparable to that of aboBoNT-A. CONCLUSIONS: Ready-to-use liquid formulation of abobotulinumtoxinA was shown to be efficacious, with comparable results to reconstituted abobotulinumtoxinA, and to have a favorable safety profile in subjects with severe to moderate GL.

Topical azithromycin for the prevention of Lyme borreliosis: a randomised, placebo-controlled, phase 3 efficacy trial.

BACKGROUND: Lyme borreliosis develops in 1-5% of individuals bitten by ticks, but with a diagnostic gap affecting up to 30% of patients, a broadly applicable pharmacological prevention strategy is needed. Topical azithromycin effectively eradicated Borrelia burgdorferi sensu lato from the skin in preclinical studies. We assessed its efficacy in human beings. METHODS: In this randomised, double-blind, placebo-controlled, multicentre trial done in 28 study sites in Germany and Austria, adults were equally assigned to receive topical 10% azithromycin or placebo twice daily for 3 consecutive days, within 72 h of a tick bite being confirmed. Randomisation numbers, which were stratified by study site, were accessed in study centres via an interactive voice-response system, by pharmacists not involved in the study. The primary outcome was the number of treatment failures, defined as erythema migrans, seroconversion, or both, in participants who were seronegative at baseline, had no further tick bites during the study, and had serology results available at 8 weeks (intention-to-treat [ITT] population). This study is registered with EudraCT, number 2011-000117-39. FINDINGS: Between July 7, 2011, and Dec 3, 2012, 1371 participants were randomly assigned to treatment, of whom 995 were included in the ITT population. The trial was stopped early because an improvement in the primary endpoint in the group receiving azithromycin was not reached. At 8 weeks, 11 (2%) of 505 in the azithromycin group and 11 (2%) of 490 in the placebo group had treatment failure (odds ratio 0·97, 95% CI 0·42-2·26, p=0·47). Topical azithromycin was well tolerated. Similar numbers of patients had adverse events in the two groups (175 [26%] of 505 vs 177 [26%] of 490, p=0·87), and most adverse events were mild. INTERPRETATION: Topical azithromycin was well tolerated and had a good safety profile. Inclusion of asymptomatic seroconversion into the primary efficacy analysis led to no prevention effect with topical azithromycin. Adequately powered studies assessing only erythema migrans should be considered. A subgroup analysis in this study suggested that topical azithromycin reduces erythema migrans after bites of infected ticks. FUNDING: Ixodes AG.

Evaluation of self-esteem and depression symptoms in depressed and nondepressed subjects treated with onabotulinumtoxinA for glabellar lines.

BACKGROUND: Botulinum toxin type A (BoNT-A) injection has become the most popular cosmetic nonsurgical procedure, and it has been suggested that BoNT-A injections may improve emotional states when frown lines are treated. OBJECTIVES: To evaluate symptoms of depression and self-esteem before and after onabotulinumtoxinA (ONA) injections in the glabella in subjects with and without depression. METHODS: Twenty-five subjects with depression were allocated into one group and 25 subjects without depression were matched to those according to demographic characteristics. The Beck Depression Inventory (BDI) and Rosenberg Self-Esteem Scale (RSES) were used to assess depression symptoms and self-esteem, respectively. Patients were assessed up to 12 weeks after the intervention. RESULTS: Patients with depression had significant improvement in depression symptoms after ONA injections. The maximum effect occurred within the first 8 weeks after treatment. A significant reduction from baseline in BDI score and significant improvement in self-esteem were also observed in patients with depression. CONCLUSION: This research presents new data regarding BoNT-A as a potential treatment to improve depression symptoms in patients with Major Depressive Disorder. Self-esteem scores alone cannot explain the improvement in depression symptoms.

Repeated botulinum toxin A injections for the treatment of lines in the upper face: a retrospective study of 4,103 treatments in 945 patients.

BACKGROUND: Although botulinum toxin type A (BoNT-A) is a common aesthetic intervention, there are few published data on treatment over more than two cycles. OBJECTIVE: To evaluate the effectiveness/safety of repeated doses of BoNT-A (Dysport, Ipsen Ltd., Slough, UK) in the upper face for reduction of wrinkles. METHODS: Retrospective, cross-sectional patient chart review from 945 patients who had received a minimum of three consecutive, documented treatment cycles. RESULTS: The glabella was treated most frequently (93.9%), with the majority (81.5%) of patients receiving treatment in more than one area of the face. BoNT-A treatments were combined with other aesthetic procedures in 57.5% of cases, mostly with fillers (37.1%). There was no evidence of tachyphylaxia: the dose applied, the interval between treatments, and satisfaction with the results remained stable over the course of treatment. Adverse events were those expected with BoNT-A treatment (most common: local bruising and ptosis) and were all mild or moderate in intensity. There was no sign of any cumulative adverse effects: indeed, the adverse-event rate decreased in later treatment cycles. CONCLUSIONS: Long-term, repeated injections of BoNT-A for corrections of wrinkles in the upper face yield a continuously high level of safety and effectiveness in actual practice.

Making scents: improvement of olfactory profile after botulinum toxin-A treatment in healthy individuals.

BACKGROUND: The axilla is particularly associated with body odor and putative pheromone production in humans. Although botulinum toxin type A (BT-A) is injected increasingly into the axillary skin to stop excessive sweating, its potential to control body odor is largely unexplored. OBJECTIVE: The objective was to measure the impact of BT-A on human axillary odor in an objective and reproducible fashion. METHODS: This study was a randomized, double-blind, placebo-controlled trial with 51 healthy volunteers receiving 50 U of BOTOX (Allergan, Inc.) in one axilla and placebo in the other. Odor quality was assessed by treated subjects (questionnaire) as well as by independent raters who were exposed to blinded T-shirt samples. RESULTS: No major side effects occurred, and no subject withdrew from the study for medical reasons. Samples from the BT-A-treated side smelled less intense (p<.001) and better (p<.001) according to self-assessments. Likewise, independent raters found the BT-A-treated samples to smell less intense and better (p<.001). They preferred "to work together with the respective person" and found the odor "more erotic" (p<.001). CONCLUSION: Side-by-side comparison of odor samples (T-shirt sniff test) by independent raters showed that axillary odor in healthy individuals is significantly more appealing after BT-A injection.

Low-dose efficacy of botulinum toxin A for axillary hyperhidrosis: a randomized, side-by-side, open-label study.

OBJECTIVE: To compare 2 doses of botulinum toxin A in view of dose-dependent efficacy, longevity, and safety. DESIGN: Side-by-side, controlled, randomized clinical trial with extended follow-up over 2 treatment cycles. Patients were injected with 200 U of botulinum toxin A (Dysport; Ipsen Ltd, Wrexham, England) into one axilla and 100 U into the other axilla in a randomized fashion. After 48 weeks of follow-up, the patients were given a second treatment with identical doses to the respective axillae and were again followed up for 48 weeks. Gravimetric measurements of sweat production and the patients' own rating of sweating were monitored. SETTING: University-based outpatient clinic. PATIENTS: Forty-three subjects with primary axillary hyperhidrosis that was unresponsive to topical therapy. MAIN OUTCOME MEASURE: Absolute values of sweat production. RESULTS: Two weeks after treatment, the sweat production was significantly reduced compared with baseline levels. Both doses were equally effective. At week 48, the sweat production had returned to baseline levels irrespective of the dose. After the second treatment, both doses were again equally effective at any follow-up point. At the end of the follow-up period (96 weeks) for the second treatment, the sweat production was significantly lower than at the end of the first follow-up period (48 weeks). The treatment was well tolerated, and there were no lasting or severe adverse effects. CONCLUSIONS: Short- and long-term results show that doses of 100 and 200 U of botulinum toxin A are equally safe and effective. However, because of cost considerations and possible adverse effects, the lower dose is preferable for treating axillary hyperhidrosis.

Double-blind, randomized, placebo-controlled, dose-response study of the safety and efficacy of botulinum toxin type A in subjects with crow's feet.

BACKGROUND: Published evidence suggests that botulinum toxin type A (BTX-A) is an effective treatment for crow's feet. However, few dose-ranging studies have been performed. OBJECTIVES: To assess the safety and efficacy of a single treatment with one of four doses of BTX-A (Botox/Vistabel, Allergan Inc) compared with placebo for the improvement of crow's feet. METHODS: Subjects received a single bilateral treatment of 18, 12, 6, or 3 U of BTX-A or placebo injected into the lateral aspect of the orbicularis oculi muscle (parallel-group, double-blind design). Investigators and subjects rated crow's feet severity at maximum smile on day 7 and at 30-day intervals from days 30 to 180. RESULTS: As observed by both investigators and subjects, all doses of BTX-A resulted in improvements in crow's feet severity when compared with placebo. A dose-dependent treatment effect for efficacy was observed, with higher doses having an increased magnitude and duration of effect. However, a clear differentiation between the 18 U and 12 U doses was not apparent. Few adverse events were reported, with no statistically significant differences between BTX-A and placebo in the incidence of subjects experiencing adverse events. CONCLUSION: BTX-A is safe and effective in decreasing the severity of crow's feet, with 12 U per side suggested as the most appropriate dose.

Details from dignity to decay: facial expression lines in visual arts.

BACKGROUND: A number of dermatologic procedures are intended to reduce facial wrinkles. This article is about wrinkles as a statement of art. OBJECTIVE: This article explores how frown lines and other facial wrinkles are used in visual art to feature personal peculiarities and accentuate specific feelings or moods. Facial lines as an artistic element emerged with advanced painting techniques evolving during the Renaissance and following periods. The skill to paint fine details, the use of light and shadow, and the understanding of space that allowed for a three-dimensional presentation of the human face were essential prerequisites. Painters used facial lines to emphasize respected values such as dignity, determination, diligence, and experience. Facial lines, however, were often accentuated to portrait negative features such as anger, fear, aggression, sadness, exhaustion, and decay. This has reinforced a cultural stigma of facial wrinkles expressing not only age but also misfortune, dismay, or even tragedy. CONCLUSION: Removing wrinkles by dermatologic procedures may not only aim to make people look younger but also to liberate them from unwelcome negative connotations. On the other hand, consideration and care must be taken-especially when interfering with facial muscles-to preserve a natural balance of emotional facial expressions.

Pharmacologic denervation of frown muscles enhances baseline expression of happiness and decreases baseline expression of anger, sadness, and fear.

BACKGROUND: Individuals with intense frowning are commonly perceived as expressing negative emotions. Anger, fear, and sadness are associated with corrugator ("frown") muscle activity. OBJECTIVE: We sought to study how faces were perceived by others after denervation of frown muscles with localized botulinum toxin injections for treatment of facial frown lines. METHODS: Facial photographs were taken from volunteers before and after botulinum toxin injection. These photographs were shown to viewers who were naive to the procedure and asked to rate the expressed intensity of anger, sadness, fear, and happiness. As reference for this task we used a standard set of pictures of facial affect displaying different intensity levels for each emotion tested. RESULTS: Of 40 viewers, 39 were able to discriminate different intensity levels (0%, 25%, 50%, 75%, and 100%) of emotional affect in the control task. According to their ratings faces with denervated frown muscle activity expressed relatively less anger (-40%), fear (-49%), sadness (-10%), and more happiness (+71%). CONCLUSION: Frown muscle activity is essential for both negative and positive emotional expressions. Temporary denervation using botulinum toxin enhances the facial expression of positive emotion resulting in a shift rather than a loss of facial affect.

Amelioration of body odor after intracutaneous axillary injection of botulinum toxin A.

BACKGROUND: Body odor is a ubiquitous phenomenon. It is commonly attributed to sweating and noted explicitly in the axillary area. Botulinum toxin A has recently been shown to be effective for axillary hyperhidrosis. Its effect on axillary odor, however, is unknown. OBSERVATIONS: Sixteen healthy volunteers were injected with botulinum toxin A (Dysport, 100 U dissolved in 0.9% sodium chloride solution) in one axilla and 0.9% sodium chloride solution in the other axilla in a randomized, double-blinded fashion. After 7 days, body odor was assessed by a T-shirt sniff test. A significant reduction of odor intensity was observed for the botulinum toxin A-treated side. The smell was also rated significantly less unpleasant. CONCLUSIONS: These findings suggest that botulinum toxin A can ameliorate or even improve body odor. The underlying mechanisms may include interference with skin microbes and denervation of apoeccrine sweat glands, but this remains to be further investigated.