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

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

The Second 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 independently assessed by both investigator and patient 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 (IT) of 20 U prabotulinumtoxinA (4 U/0.1 mL final vacuum-dried formulation injected into 5 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 outcomes were evaluated throughout the study. RESULTS: The 570 study patients received a median total dose of 60 U, that is, 3 treatments. Sixty-one patients (10.7%) experienced adverse events (AEs) assessed as possibly study drug related; 6.5% experienced study drug-related AEs after the IT. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Eight patients (1.4%) experienced study drug-related AEs of special interest: 5 experienced eyelid ptosis (0.9%), 3 eyebrow ptosis (0.5%), 1 blepharospasm (0.2%), and 1 blurred vision (0.2%). Seven patients (1.2%) experienced serious AEs, but none were study drug related. A total of 4060 serum samples were tested for antibotulinum toxin antibodies; no seroconversion was observed. CONCLUSIONS: The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was confirmed in this second phase II study based on a broad range of outcomes.

Efficacy and Safety of PrabotulinumtoxinA for the Treatment of Glabellar Lines in Adult Subjects: Results From 2 Identical Phase III Studies.

BACKGROUND: PrabotulinumtoxinA is a 900-kDa botulinum toxin Type A produced by Clostridium botulinum. OBJECTIVE: To investigate the efficacy and safety of prabotulinumtoxinA for the treatment of glabellar lines. MATERIALS AND METHODS: Adult subjects (n = 330 in EV-001; n = 324 in EV-002) with moderate to severe glabellar lines at maximum frown on the 4-point Glabellar Line Scale (GLS; 0 = no lines, 1 = mild, 2 = moderate, and 3 = severe) were enrolled in 1 of 2 identical 150-day, double-blind, placebo-controlled, single-dose, Phase III studies. Subjects were randomized 3:1 to receive 20-U prabotulinumtoxinA or placebo. The primary efficacy end point was the proportion of responders on Day 30 where the investigator and subject independently agreed that a ≥2-point improvement had occurred on the GLS at maximum frown from Day 0. Adverse events (AEs) were evaluated throughout the study. RESULTS: Responder rates in the prabotulinumtoxinA and placebo groups were 67.5% and 1.2% in EV-001 and 70.4% and 1.3% in EV-002; absolute differences between groups were 66.3% and 69.1% in EV-001 and EV-002, respectively (both p < .001). No serious AE in either study was assessed as study drug related. CONCLUSION: In these studies, a single dose of 20-U prabotulinumtoxinA was safe and effective for the treatment of glabellar lines.

Identification and management of mental health issues by dermatologic surgeons: a survey of American Society for Dermatologic Surgery members.

BACKGROUND: Dermatologists have long been interested in mental health issues of their patients. Some psychosocial distress likely motivates the pursuit of cosmetic dermatologic treatments. However, a percentage of patients seeking treatment suffer from significant psychopathology, such as body dysmorphic disorder (BDD), which may contraindicate treatment. OBJECTIVE: To assess dermatologic surgeons' strategies for identification and management of mental health issues among patients seeking cosmetic procedures. MATERIALS AND METHODS: A survey was sent to 2,855 practicing members of the American Society for Dermatologic Surgery by e-mail. RESULTS: Two hundred sixty members completed the survey (9.1%). Approximately, 60% of respondents indicated that they ask new patients about psychiatric treatment history, and 92% reported that they have declined to provide a cosmetic treatment because of concerns about mental health status. Most (94%) indicated that they were aware of BDD, and 62% indicated that they refused to treat a patient believed to have BDD. Respondents estimated that 13% of new patients had BDD and 63% considered BDD to be a contraindication to treatment. CONCLUSION: Approximately 60% of dermatologic surgeons inquire about the mental health issues of their cosmetic patients. Most are aware of BDD, but less than two-thirds consider it a contraindication to treatment.

Aesthetic treatment considerations for the eyebrows and periorbital complex.

The periorbital complex is a critical cosmetic unit. Treatments for this region range from topical prescriptions to enhance the brow hair to topical cosmeceuticals that improve the tone and texture of the skin. Lasers, radiofrequency, botulinum toxins, fillers, and a host of other treatments are used to treat the periorbital region. Judicious use of these treatments, alone or in combination, can greatly alter the appearance of the region. However, adverse events may also be associated with these treatments, and the clinician and patients need to consider both the risks and the benefits of treatment prior to embarking upon a regimen.

Treatment of eyebrow hypotrichosis using bimatoprost: a randomized, double-blind, vehicle-controlled pilot study.

BACKGROUND: The Food and Drug Administration has approved bimatoprost ophthalmic solution (0.03%) for the treatment of eyelash hypotrichosis. Previous reports of its efficacy in eyebrow hypotrichosis are anecdotal. OBJECTIVE: To assess the efficacy and safety of bimatoprost 0.03% ophthalmic solution applied to the eyebrows in a randomized, double-blind, vehicle-controlled study. METHODS: Subjects (n = 20) with mild to moderate eyebrow hypotrichosis enrolled in the study. One group (Bim) applied bimatoprost to each eyebrow daily for 9 months, and another applied vehicle nightly to each eyebrow for 5 months. Subjects in the latter group were re-randomized to apply bimatoprost (Veh-Bim Group) or vehicle (Veh Group) daily to each eyebrow for 4 months. The primary end point was investigator-assessed eyebrow appearance; secondary end points were subject-reported outcomes. RESULTS: Investigator assessments showed significant improvements from baseline to 6 (p = .002) and 7 (p = .005) months for the eyebrows treated with bimatoprost. p-Values for the Veh-Bim and Veh groups were not significant at any time point. End-of-study subject satisfaction with eyebrow fullness or thickness and darkness or color was greater in the Bim group than in the Veh group. Adverse effects were not observed. CONCLUSION: Bimatoprost 0.03% ophthalmic solution applied daily for 9 months improves the appearance of eyebrows noticeably more than vehicle, without side effects.

Treatment of margin positive basal cell carcinoma with vismodegib: case report and consideration of treatment options and their implications.

Historically, basal cell carcinomas (BCCs) that are neither surgically resectable nor candidates for radiation therapy have had few treatment options. The hedgehog pathway inhibitor, vismodegib, represents a new opportunity for the treatment of such patients. Vismodegib has approval from the United States Food and Drug Administration for treatment of metastatic BCC, locally advanced BCC recurring after surgery, and BCC that is not treatable via surgery or radiation. We present the case of a patient with a BCC infiltrating the spinal column that was neither possible to fully remove surgically nor a candidate for primary treatment with radiation. Treatment with vismodegib followed by adjuvant radiation therapy resulted in complete disease clearance. Vismodegib represents a promising treatment option for patients with surgically non-resectable BCCs that are not candidates for radiation therapy. Mechanism of action, benefits, and adverse events of vismodegib are reviewed, along with a brief discussion on newer options in the hedgehog inhibitor class.

PrabotulinumtoxinA for the treatment of glabellar lines in adults, 65 years of age and older: The fourth in a series of post hoc analyses of the phase III clinical study data.

BACKGROUND: Despite the absence of Phase III clinical trial data to support their use, 3.4% of all neurotoxin treatments performed internationally for esthetic purposes in 2020 were performed in patients 65 years of age and older. OBJECTIVES: To investigate the efficacy and safety of prabotulinumtoxinA for the treatment of moderate to severe glabellar lines in the subset of Phase III clinical trial participants who were 65 years of age and older. METHODS: Post hoc analyses were performed on all patients who had been treated with a single dose of 20 U prabotulinumtoxinA in the three 150-day, placebo-controlled Phase III glabellar line clinical studies. Patients were grouped by age: ≥65 years (n = 70) versus <65 years (n = 667). The endpoints of primary interest were the proportion of responders with a ≥1-point improvement from baseline at maximum frown on the 4-point Glabellar Line Scale and treatment-related adverse events. RESULTS: For the efficacy endpoint of primary interest, responder rates among patients 65 years of age and older were numerically less than those of patients less than 65 years by an absolute mean difference of just -2.7% across all visits; none of the differences at any visit were statistically significant. The most common treatment-related adverse event was headache, occurring in 5.7% of those 65 years of age and older and in 9.7% of those less than 65 years. CONCLUSIONS: 20 U prabotulinumtoxinA administered for the treatment of glabellar lines was efficacious in patients 65 years of age and older; it was also well tolerated by this cohort.

Combined treatment for skin rejuvenation and soft-tissue augmentation of the aging face.

Multiple types of anti-aging treatments are required to address the various etiologies of facial aging. Soft-tissue augmentation provides a minimally invasive option for patients seeking to look younger. However, due to changes in facial skin, musculature, fat and bone, anti-aging treatment requires a multifaceted approach. Injectable fillers may be combined with neurotoxins to resolve superficial wrinkles and restore facial volume. These modalities may be used with laser resurfacing or chemical peels to address epidermal and superficial dermal problems. Combining injectable soft-tissue augmentation treatments allows clinicians and patients to take advantage of the benefits of each modality and to address the multiple effects of facial aging. This review is based on clinical experience and a MEDLINE search for articles about volume replacement and soft-tissue augmentation. It provides a rationale that supports the use of combination techniques/products for soft-tissue augmentation.

Rapid onset of response and patient-reported outcomes after onabotulinumtoxinA treatment of moderate-to-severe glabellar lines.

INTRODUCTION: no previously published botulinum toxin type A cosmetic trials included both physician and subject measures of onset. OBJECTIVE: determine physician- and subject-reported onset of onabotulinumtoxinA. METHODS: Two-center open-label, 14-day study in toxin-naive female patients with moderate-to-severe glabellar lines (GL) treated with 20-U onabotulinumtoxinA. Onset endpoint was categorical (physician assessed: days 2, 3, 4, 7 and 14; subject: 14-day diary). Subjects rated improvements in GL severity and completed the Facial Line Outcomes (FLO) and Self-Perception of Age (SPA) questionnaires. RESULTS: nearly half, 48 percent (n=45) of subjects, reported onset by day 1. Subject- and physician-reported onset rates, respectively, were 77 percent and 87 percent (day 2), 93 percent and 91 percent (day 3), 98 percent and 100 percent (day 4), and 100 percent thereafter. At all time points, FLO and SPA improved (P=0.008 and P=0.01, respectively). No serious adverse events occurred. CONCLUSION: onabotulinumtoxinA provides rapid onset (one to two days) based on physician and subject assessment.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: results of two placebo-controlled studies of daily application to the face and balding scalp for two 3-week cycles.

BACKGROUND: Imiquimod 5% cream is approved as a 16-week regimen for the treatment of actinic keratoses involving a 25-cm(2) area of skin. OBJECTIVE: We sought to evaluate imiquimod 2.5% and 3.75% creams for short-course treatment of the entire face and scalp. METHODS: In two identical studies, adults with 5 to 20 lesions were randomized to placebo, or imiquimod 2.5% or 3.75% cream (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 3-week treatment cycles, with a 3-week, no-treatment interval. Efficacy was assessed at 8 weeks posttreatment. RESULTS: In all, 490 subjects were randomized to placebo, or imiquimod 2.5% or 3.75% cream. Median baseline lesion counts for the treatment groups were 9 to 10. Complete and partial clearance rates were 5.5% and 12.8% for placebo, 25.0% and 42.7% for imiquimod 2.5%, and 34.0% and 53.7% for imiquimod 3.75% (P < .001, each imiquimod vs placebo; P = .034, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion count were 23.6%, 66.7%, and 80.0% for the placebo, imiquimod 2.5%, and imiquimod 3.75% groups, respectively (P < .001 each imiquimod vs placebo). There were few treatment-related discontinuations. Temporary treatment interruption (rest) rates were 0%, 17.1%, and 27.2% for the placebo, imiquimod 2.5%, and imiquimod 3.75%, respectively. LIMITATIONS: Local effects of imiquimod, including erythema, may have led to investigator and subject bias. CONCLUSIONS: Both imiquimod 2.5% and 3.75% creams were more effective than placebo and had an acceptable safety profile when administered daily as a 3-week on/off/on regimen.

An open-label trial examining the efficacy and safety of a pre- and postprocedure topical five-product system (Clinique Medical Optimizing Regimen) specifically formulated to complement laser/light-based facial cosmetic procedures.

BACKGROUND: Specialized skin care regimens may help to minimize adverse events (AEs) following non-ablative facial procedures. METHODS: A 14-week, open-label, three-center study evaluated the efficacy and safety of a topical five-product system (Clinique Medical Optimizing Regimen; Allergan, Inc., Irvine, CA, USA) for minimizing localized AEs during two 6-week procedure cycles with fractionated laser (FL) or intense pulsed light (IPL). The skin care regimen consisted of a 2-week preprocedure phase, a 1-week postprocedure phase, and a 3-week maintenance phase. Investigators and patients rated the presence and severity of erythema, itching, stinging/burning, edema, pain, pruritus, swelling, crusts/erosion, and photodamage. RESULTS: Two days after the FL/IPL treatment (IPL: n = 27; FL: n = 21), most assessments, including erythema, were near baseline values; at 4 weeks postprocedure, all investigator scores were comparable to baseline. Patients missed work or avoided social situations a mean of only 0.8 days. Mean subject ratings for itching, stinging/burning, pain, swelling, and redness for 2 weeks postprocedure were 'none' to 'mild'. Treatment-related AEs (acne, facial rash) occurred in four patients. All investigators stated they would recommend this topical over-the-counter regimen again in conjunction with non-ablative FL/IPL treatments. CONCLUSIONS: This topical five-product skin care system was safe and effective in conjunction with non-ablative FL/IPL procedures.

Nipple contouring with hyaluronics postmastectomy.

The lack of a naturally shaped nipple-areola complex following mastectomy presents a significant psychological hindrance for many breast cancer patients. While tattoos may improve the overall color of the reconstructed breast, the shape of the areola-nipple complex frequently remains deformed. Injecting hyaluronic acid may enable the 3-dimension contour of this area to be restored to a more natural appearance. This restoration may be associated with improvement of self-image and reduction in the depression that sometimes follows a mastectomy.

Nasal reconstruction using 20 mg/ml cross-linked hyaluronic acid.

According to American Society for Aesthetic Plastic Surgery (ASAPS), 200,924 people had rhinoplasties in 2005. Patients typically have surgical rhinoplasty to correct unsightly noses resulting from trauma, surgery, or heredity. Several alternatives presently exist for patients considering surgical rhinoplasty. These include injections of botulinum toxins to correct the shape of the nasal tip and the use of various fillers to correct contour and profile defects. This article presents a simple and effective alternative using hyaluronic acid for some patients requiring nasal recontouring. The procedure offers patients the opportunity to avoid the risks and expense associated with surgical correction.

Use of sculptra mark in esthetic rejuvenation.

The addition of Sculptra to the esthetic dermatology landscape in September 2004 brought a new opportunity for facial rejuvenation. Sculptra, which is polymerized lactic acid (PLA), received approval from the Food and Drug Administration for the treatment of HIV-associated lipoatrophy. Since its approval, it has gained acceptance among cosmetic dermatologists and plastic surgeons, and its inclusion in any update of esthetic dermatology is certainly warranted. Its uses for esthetic indications are now being substantiated by clinical trials and, as experience with this product increases, it is likely that it will be more widely used for these reasons.