Submental Area Treatment with ATX-101: Relationship of Mechanism of Action, Tissue Response, and Efficacy.

ATX-101 is an injectable, synthetically derived formulation of deoxycholic acid used for submental fat reduction. Methods: A narrative review of references relevant to the mechanism of action of ATX-101 and its relationship to efficacy and inflammatory adverse events was conducted. Results: When injected into subcutaneous fat, deoxycholic acid physically disrupts adipocyte cell membranes, leading to local adipocytolysis, cell death, and a mild, local inflammatory reaction consisting of macrophage infiltration and fibroblast recruitment. At Day 28 postinjection, inflammation largely resolves, and key histologic features include fibrotic septal thickening, neovascularization, and atrophy of fat lobules. Based on the mechanism of action of ATX-101 and the demonstrated inflammatory response, localized inflammation and swelling are expected following treatment. Indeed, postinjection swelling and other local injection-site events, including pain, erythema, and bruising, are common during and after treatment. Because of inflammatory sequelae following injection, reduction in submental fat is gradual and may require months before the full response is apparent. Patients may also require multiple treatment sessions to achieve their treatment goals. Repeated treatments may result in less pain and swelling over time owing to a combination of factors, including less target tissue allowing for lower doses/injection volumes, persistent numbness, and greater tissue integrity from thickened fibrous septa. Conclusions: Physicians can manage expectations by counseling patients that, based on the mechanism of action of ATX-101 and data from pivotal clinical trials, ATX-101 treatment results in localized inflammation/swelling and gradual submental fat reduction. Patient education about common local adverse events is critical.

OnabotulinumtoxinA for Simultaneous Treatment of Upper Facial Lines: Subject-Reported Satisfaction and Impact From a Phase 3 Study.

BACKGROUND: Patient-reported outcomes are increasingly recognized as important measures of treatment benefit. OBJECTIVE: To evaluate subject-reported satisfaction and impact outcomes with onabotulinumtoxinA treatment in neurotoxin-naive adults with forehead lines (FHL), glabellar lines (GL), and crow's feet lines (CFL). METHODS: This Phase 3 study randomized 787 subjects to onabotulinumtoxinA 64 U (FHL 20 U, GL 20 U, and CFL 24 U), 40 U (FHL 20 U, GL 20 U, and CFL placebo), or placebo in double-blind Period 1. Subjects could receive up to 2 additional 64 U treatments in open-label Period 2. Patient-reported outcomes were assessed using the validated Facial Line Satisfaction Questionnaire (FLSQ) and 11-item Facial Line Outcomes (FLO-11) Questionnaire. RESULTS: The proportion of subjects mostly or very satisfied was significantly greater with onabotulinumtoxinA 64 U and 40 U versus placebo (87.9% and 81.4% vs 3.2%; p < .0001). Responder rates on FLSQ Impact Domain, FLO-11 Items 1, 4, 5, and total score were significantly greater with onabotulinumtoxinA versus placebo on Day 30 (p < .0001). Responder rates favoring onabotulinumtoxinA in Period 1 were maintained with repeated onabotulinumtoxinA 64 U treatment in Period 2. CONCLUSION: OnabotulinumtoxinA treatment was associated with high subject satisfaction and significant improvements in appearance-related psychological and emotional impacts.

Pooled Subject-Reported Outcomes From 2 Phase 3 Studies of OnabotulinumtoxinA for Simultaneous Treatment of Forehead and Glabellar Lines.

BACKGROUND: Understanding the subjects' perspective is critical for successfully treating upper facial lines. OBJECTIVE: To understand subjects' self-perception and overall satisfaction after onabotulinumtoxinA treatment for forehead and glabellar lines. METHODS: This analysis pooled data from two 12-month, pivotal phase 3 studies in which toxin-naive subjects received onabotulinumtoxinA 40 U or placebo for treatment of upper facial lines. OnabotulinumtoxinA was administered as 0.1-mL injections at 10 prespecified sites (frontalis: 20 U; glabellar complex: 20 U). Each study used 3 reliable and validated patient-reported outcome instruments to evaluate subject satisfaction and appearance-related psychological effects: the Facial Line Satisfaction Questionnaire (FLSQ), the Facial Line Outcomes (FLO-11) Questionnaire, and the Self-Perception of Age (SPA) Questionnaire. In total, data for 865 subjects (608, onabotulinumtoxinA 40 U; 257, placebo) were analyzed. RESULTS: Treatment with onabotulinumtoxinA 40 U resulted in significant and sustained improvements across all pooled FLO-11 items and FLSQ items compared with placebo. SPA results demonstrated that a significant proportion of subjects in the pooled analysis felt they looked younger after treatment than at baseline (all, p < .0001 vs placebo). CONCLUSION: This study demonstrates a high level of treatment satisfaction and significantly improved appearance-related psychological outcomes among toxin-naive subjects after onabotulinumtoxinA 40 U treatment.

OnabotulinumtoxinA for Treatment of Forehead and Glabellar Lines: Subject-Reported Satisfaction and Impact From a Phase 3 Double-Blind Study.

BACKGROUND: Patient-reported outcomes are important measures of treatment benefit in facial aesthetic medicine. OBJECTIVE: Evaluate prespecified subject-reported satisfaction and impact outcomes with onabotulinumtoxinA treatment of forehead lines (FHL) and glabellar lines (GL). METHODS: The study randomized (3:1) 391 adults with moderate to severe FHL and GL to onabotulinumtoxinA (FHL, 20 U; GL, 20 U) or placebo in double-blind period 1 (days 0-180); subjects could receive up to 2 additional onabotulinumtoxinA treatments in open-label period 2. Patient-reported outcomes were assessed using the validated Facial Line Satisfaction Questionnaire (FLSQ) and the 11-item Facial Line Outcomes (FLO-11) Questionnaire. RESULTS: The proportion of subjects mostly or very satisfied with treatment was significantly greater with onabotulinumtoxinA than with placebo (90.3% vs 1.0%; p < .0001). Responder rates on FLSQ Impact Domain (73.9% vs 18.9%), FLO-11 Item 1 (85.4% vs 3.6%), Item 4 (77.2% vs 11.2%), Item 5 (83.5% vs 7.8%), and total score (86.0% vs 6.9%) were significantly greater with onabotulinumtoxinA than with placebo on Day 30 (p < .0001). Responder rates favoring onabotulinumtoxinA in Period 1 were generally maintained with repeated treatment during Period 2. CONCLUSION: Subjects were highly satisfied with onabotulinumtoxinA treatment and reported significant improvements in appearance-related psychological and emotional impacts of their facial lines.

The Psychological Impacts of Upper Facial Lines: A Qualitative, Patient-Centered Study.

BACKGROUND: The 11-item Facial Line Outcomes (FLO-11) questionnaire is content validated for measuring the negative psychological impacts of crow's feet lines (CFL). OBJECTIVES: The aims of this study were to determine psychological impacts of forehead lines (FHL) alone and upper facial lines (UFL: FHL + CFL + glabellar lines [GL]) and to assess adequacy of FLO-11 to measure these impacts. METHODS: Participants aged at least 18 years participated in concept elicitation and cognitive interviews to identify and define psychological impacts of UFL. They completed the FLO-11 questionnaire to assess its ability to measure psychological impacts of facial lines and its comprehensiveness in doing so. RESULTS: Forty interviews were completed by 29 participants. Twenty participants each provided interviews for FHL and for UFL. The most commonly reported psychological impacts for FHL and UFL, respectively, were feeling unattractive (85%, 80%), looking less attractive than desired (85%, 70%), feeling bothered (80%, 70%), feeling good/bad about appearance (80%, 70%), looking older than actual age (75%, 65%), and feeling stressed (70%, 70%). For FHL, 70% of participants also reported looking older than desired as a psychological impact. More than 50% of participants agreed that all 11 FLO-11 items measured a psychological impact for FHL. More than 50% reported that 9 of 11 items measured a psychological impact for UFL. The majority of participants (FHL, 65%; UFL, 60%) reported that the FLO-11 questionnaire is comprehensive in measuring psychological impacts of facial lines. CONCLUSIONS: FHL and UFL have psychological impacts on patients, and FLO-11 is a content valid, comprehensive instrument for measuring them.

An evaluation of the safety and efficacy of bimatoprost for eyelash growth in pediatric subjects.

PURPOSE: Evaluate the safety and effectiveness of bimatoprost 0.03% for treatment of eyelash hypotrichosis in a pediatric population. PATIENTS AND METHODS: This multicenter, randomized, double-masked, parallel-group study was conducted at seven sites in the US and Brazil. Subjects with eyelash hypotrichosis caused by chemotherapy or alopecia areata (aged 5-17 years) or healthy adolescents aged 15-17 years were enrolled (N=71). Subjects applied bimatoprost 0.03% or vehicle to upper eyelid margins once nightly for 4 months and were followed for 1 month post-treatment. Eyelash prominence was assessed using the validated 4-grade Global Eyelash Assessment scale with photonumeric guide. Changes in eyelash length, thickness, and darkness were measured by digital image analysis. Safety was assessed by adverse events and ophthalmic observations. RESULTS: Eyelash prominence improved in a significantly greater proportion of subjects treated with bimatoprost compared with vehicle at month 4 (70.8% versus 26.1%; P<0.001). This benefit was sustained at month 5 post-treatment assessment. Digital image analysis measures were significantly improved with bimatoprost. Significant treatment benefits with bimatoprost versus vehicle were evident among the healthy adolescents but not in the postchemotherapy or alopecia areata subgroups. The safety profile of bimatoprost was consistent with previous studies in adults. CONCLUSION: Bimatoprost was safe and well tolerated in pediatric subjects with eyelash hypotrichosis. In this study with limited sample size, subgroup analyses showed that treatment was effective in healthy adolescents with no concurrent contributing medical condition, but not in those with eyelash hypotrichosis due to chemotherapy or alopecia areata.

Bimatoprost 0.03% for the Treatment of Eyelash Hypotrichosis: A Pooled Safety Analysis of Six Randomized, Double-masked Clinical Trials.

OBJECTIVE: Describe the safety profile of bimatoprost 0.03% ophthalmic solution as once-daily topical treatment for idiopathic or chemotherapy-induced eyelash hypotrichosis. DESIGN: Pooled data from six randomized, multicenter, double-masked, parallel-group clinical studies of at least three-months' duration with at least one bimatoprost treatment group. SETTING: Study sites in the United States, Canada, United Kingdom, and Japan from 2007 to 2012. PARTICIPANTS: Adults with eyelash hypotrichosis, defined as baseline Global Eyelash Assessment of minimal or moderate, who received bimatoprost 0.03% (n=680) or vehicle, with no prior exposure to bimatoprost (n=379). MEASUREMENTS: Safety assessments included adverse events, vital sign measurements, and physical examinations. Common (≥2%) and treatment-related adverse events were analyzed at time points up to four months and through end of treatment, up to 12 months. RESULTS: Similar overall adverse events incidence was reported in bimatoprost and vehicle groups for subjects with idiopathic hypotrichosis; a higher incidence in both groups was reported for postchemotherapy subjects. Common adverse events included conjunctival hyperemia, eyelid pruritus, blepharal pigmentation, nasopharyngitis, eyelid erythema, and punctate keratitis. Most adverse events occurred early in treatment, were mild in intensity, localized to treatment site, and reversible with treatment cessation. Discontinuations due to adverse events were low (3.2% for bimatoprost and 2.4% for vehicle). CONCLUSION: Adverse events were consistent with the known pharmacologic mechanism of bimatoprost. The safety profile was similar across the studies and no new safety signals were observed. Once-daily bimatoprost 0.03% for treatment of eyelid hypotrichosis has a favorable safety and tolerability profile when applied topically to the upper eyelid margin.

A retrospective review and observational study of outcomes and safety of bimatoprost ophthalmic solution 0.03% for treating eyelash hypotrichosis.

BACKGROUND: The efficacy and safety of bimatoprost ophthalmic solution 0.03% for treating hypotrichosis were shown in a randomized controlled trial and in an open-label study. To date, no data on real-world experience have been published. OBJECTIVE: To evaluate long-term patient satisfaction, usage patterns, and safety of bimatoprost 0.03% in clinical practice. MATERIALS AND METHODS: In this retrospective chart review with a cross-sectional design, adult patients exposed to bimatoprost 0.03% for at least 12 months were randomly sampled from 16 investigational sites. Charts were reviewed for medication usage characteristics and adverse events (AEs). At a study visit, questionnaires eliciting patient-reported outcomes were administered and spontaneously reported AEs were tabulated. RESULTS: Analysis included 585 subjects with a mean (SD) treatment duration of 19.3 (4.3) months. Patient satisfaction with bimatoprost 0.03% was 92.5%; on average, approximately 3 applications per week maintained benefits. Overall, 27.4% of patients spontaneously recalled experiencing AEs while on treatment; however, patient charts showed that only 4 AEs were documented. No instances of iris hyperpigmentation occurred. No serious or severe AEs were noted. CONCLUSION: Treatment with bimatoprost 0.03% for at least 12 months is safe, and long-term use is associated with a high degree of satisfaction.