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.

Lip and Perioral Enhancement With Hyaluronic Acid Dermal Fillers in Individuals With Skin of Color.

BACKGROUND: Individuals with skin of color are underrepresented in studies of lip and perioral enhancement. OBJECTIVE: To examine the effectiveness and safety of hyaluronic acid (HA) dermal filler treatment for lip and perioral enhancement in subjects with skin of color. METHODS: Data were pooled from subjects with Fitzpatrick skin phototypes IV, V, or VI in 2 pivotal studies of HA dermal fillers. Photonumeric scales were used to assess lip fullness (5-point scale) and perioral lines and oral commissures severity (each 4-point scales). Safety was assessed by injection site responses recorded in patient diaries and adverse events (AEs). RESULTS: The cohort comprised 72 subjects (median age: 49.5 years; 95.8% female). Mean lip fullness improved from baseline by 1.1 points at 3 months after treatment; 85.0% of subjects were responders (≥1-point improvement). Of subjects treated for perioral lines (n = 12) and oral commissures (n = 56), 90.9% and 46.4%, respectively, were responders. Injection site responses were generally mild or moderate in severity, resolved within 2 weeks, and were consistent with those expected for HA dermal filler treatment. The most common AEs were injection site mass (19.4%) and bruising (12.5%). CONCLUSION: Lip and perioral enhancement with HA dermal fillers is effective and safe in subjects with skin of color.

BPX-01 Minocycline Topical Gel Shows Promise for the Treatment of Moderate-to-severe Inflammatory Acne Vulgaris.

Background and objectives: Acne vulgaris is a highly prevalent and multifactorial skin disorder that can adversely impact health-related quality of life. Factors that contribute to the pathogenesis of acne include pilosebaceous proliferation of proinflammatory Propionibacterium acnes (P. acnes) bacteria, presence of circulating androgens, excess sebum production, abnormal follicular keratinization, and multiple inflammatory cascades. Oral tetracyclines-especially doxycycline and minocycline-are frequently prescribed for the treatment of moderate-to-severe acne, given their anti-inflammatory properties and their effect on P. acnes reduction. Notwithstanding their established efficacy in the management of acne vulgaris, there is a desire to limit systemic exposure to antibiotics given growing concerns regarding bacterial resistance as well as the potential for serious side effects. This report describes outcomes of two randomized, vehicle-controlled trials (Phases IIa and IIb) of BPX-01, a topical minocycline gel, in the treatment of moderate-to-severe acne. Methods: In Study 1 (NCT02709096), at a single center, 33 subjects with highly fluorescing facial skin were randomized 2:1 to BPX-01 1% or vehicle control once-daily treatment for four weeks. Changes in P. acnes quantitative bacteriological cultures were assessed, as well as cutaneous tolerance to the study drug by both subjects and the investigator. In Study 2 (NCT02815332), subjects with moderate-to-severe inflammatory nonnodular acne (n=226) at 15 centers were randomized 1:1:1 to treatment with BPX-01 1%, BPX-01 2%, or vehicle control once-daily for 12 weeks. The primary endpoint was reduction in the number of inflammatory lesions; other endpoints included the number of noninflammatory lesions, Investigator's Global Assessment (IGA) of severity, and subjective ratings (investigator and subject) of acne. In both studies, cutaneous tolerability and safety were assessed, and plasma minocycline levels were tracked with a highly sensitive assay. Results: In Study 1, BPX-01 treatment reduced P. acnes colonization by 90.9 percent, which exceeded the reduction in the vehicle control group (65.53%; p=0.020). In Study 2, treatment with BPX-01 2% reduced the number of inflammatory lesions by 58.5 percent, exceeding the reduction in the vehicle control group (43.8%; p=0.0256). Trends toward an improvement preferential to BPX-01 2% were observed in the other endpoints. Across both studies, BPX-01 treatment was well-tolerated, with no photosensitivity, postinflammatory hyperpigmentation, or skin discoloration reported. A single subject (out of 259 study participants ) was identified to have detectable levels of plasma minocycline at low levels (42ng/mL) after 12 weeks of treatment but had no signs or symptoms associated with systemic administration of minocycline. Conclusion: BPX-01 appears to exhibit an effectiveness profile for reduction of inflammatory (nonnodular) acne lesions similar to that of oral minocycline formulations. However, because BPX-01 is topical and exhibits negligible systemic exposure, the likelihood of adverse events associated with oral minocycline use is much lower. These results demonstrate effectiveness of BPX-01 topical minocycline gel in reducing P. acnes colonization, suggesting that the BPX-01 2% formulation is a promising treatment for moderate-to-severe nonnodular, inflammatory acne vulgaris in both reduction of inflammatory lesions and also overall improvement in facial acne according to IGA.

Efficacy, Safety, and Tolerability of Topical Dapsone Gel, 7.5% for Treatment of Acne Vulgaris by Fitzpatrick Skin Phototype.

BACKGROUND: Acne vulgaris (acne) is prevalent in individuals with skin of color, often with more frequent sequelae than in patients with lighter skin color. It is important to determine if there are also differences in response to medications. OBJECTIVE: This study evaluated the efficacy and tolerability of once-daily dapsone gel, 7.5% in patients with acne, stratified by Fitzpatrick skin phototype. METHODS: Data were pooled from 2 identically designed, phase 3, randomized, double-blind, vehicle-controlled studies in patients aged 12 years and older with moderate acne. Patients applied dapsone gel, 7.5% or vehicle once daily for 12 weeks. Efficacy was evaluated using the Global Acne Assessment Score (GAAS), lesion counts, and Acne Symptom and Impact Scale (ASIS); adverse events (AEs) and tolerability were also assessed. RESULTS: This analysis included 2216 patients with skin phototypes I-III and 2111 with types IV-VI. Dapsone gel, 7.5% significantly improved acne severity versus vehicle in both skin phototype subgroups, as determined by the percentage of patients with at least a 1-grade improvement in GAAS and mean change from baseline in GAAS (both, P less than .0001) at week 12 versus baseline. Dapsone gel, 7.5% significantly reduced inflammatory, comedonal, and total lesions in skin phototypes I-III (P less than .001) and IV-VI (P less than equal to .01) versus vehicle. Improvements in inflammatory lesions occurred first, with generally similar patterns of improvement seen over time in GAAS, comedonal lesions, and ASIS domains. The incidence of AEs was similar in both skin phototype subgroups and between study medications. Local scaling, erythema, stinging/burning, and dryness were rated "none" by most patients in both treatment groups and skin phototype subgroups. CONCLUSION: Once-daily dapsone gel, 7.5% was effective, safe, and well tolerated in patients with all skin phototypes who were treated for moderate acne. J Drugs Dermatol. 2018;17(2):160-167.

Global Updates on the Future Directions of Neurotoxins and Fillers.

Neurotoxins and fillers continue to remain in high demand, comprising a large part of the growing business of cosmetic minimally invasive procedures. Multiple Food and Drug Administration-approved safe yet different products exist within each category, and the role of each product continues to expand. The authors review the literature to provide an overview of the use of neurotoxins and fillers and their future directions.

Rejuvenating Hydrator: Restoring Epidermal Hyaluronic Acid Homeostasis With Instant Benefits.

Skin aging is a combination of multifactorial mechanisms that are not fully understood. Intrinsic and extrinsic factors modulate skin aging, activating distinctive processes that share similar molecular pathways. One of the main characteristics of youthful skin is its large capacity to retain water, and this decreases significantly as we age. A key molecule involved in maintaining skin hydration is hyaluronic acid (HA). Concentration of HA in the skin is determined by the complex balance between its synthesis, deposition, association with cellular structures, and degradation. HA bio-equivalency and bio-compatibility have been fundamental in keeping this macromolecule as the favorite of the skincare industry for decades. Scientific evidence now shows that topically applied HA is unable to penetrate the skin and is rapidly degraded on the skin surface. SkinMedica's HA5 Rejuvenating Hydrator (SkinMedica Inc., an Allergan company, Irvine, CA) promotes restoration of endogenous epidermal HA homeostasis and provides instant smoothing and hydration of the skin. These dual benefits are accomplished through the combination of 2 breakthrough technologies: 1) a unique blend of actives powered by SkinMedica proprietary flower-derived stem cell extract that restores the endogenous production of HA; and 2) a proprietary mix of 5 HA forms that plump the skin, decreasing the appearance of fine lines/wrinkles. Pre-clinical studies demonstrated that HA5 induces expression of key epidermal differentiation and barrier markers as well as epidermal HA synthases. A decrease expression of hyaluronidases was also observed upon HA5 application. Initial clinical studies showed that within 15 minutes of application, HA5 instantly improves the appearance of fine lines/wrinkles and skin hydration. Subjects that continue using HA5 (for 8 weeks) demonstrated significant improvements in fine lines/wrinkles, tactile roughness, and skin hydration. In summary, the blend of these 2 key technologies present in HA5 promotes restoration of endogenous epidermal HA while delivering instant smoothing effects.

Safety and Effectiveness of the Hyaluronic Acid Filler, HYC-24L, for Lip and Perioral Augmentation.

BACKGROUND: Hyaluronic acid gels are increasingly used for augmentation of the lips. OBJECTIVE: To assess the safety and effectiveness of Juvéderm Ultra XC, a 24 mg/mL hyaluronic acid gel containing 0.3% (wt/wt) lidocaine (HYC-24L), for augmentation of the lips. METHODS: This ongoing, multicenter, single-blind study randomized 213 subjects to the treatment group (n = 157) or concurrent no-treatment control group that received delayed treatment (n = 56). The primary effectiveness endpoint was the responder rate (≥1 point improvement from baseline) based on the blinded evaluating investigator's assessment of the subject's overall lip fullness (or fullness of the eligible lip) using the validated Allergan 5-point Lip Fullness Scale. To meet this endpoint, the treatment group had to have a responder rate ≥60% and significantly greater than the treatment control group at Month 3. RESULTS: The primary endpoint was met, with a 79.1% responder rate for the treatment group and 26.1% for the treatment control group (p < 0.0001). More than half of subjects (56.4%) maintained treatment response for 12 months. Common injection site responses were swelling, bruising, and firmness; most were of mild or moderate severity. CONCLUSION: HYC-24L is safe and effective for aesthetic lip augmentation, with results lasting up to 1 year.

A multicenter study of the safety and effectiveness of hyaluronic acid with a cohesive polydensified matrix for treatment of nasolabial folds in subjects with Fitzpatrick skin types IV, V, and VI.

BACKGROUND: Although the use of the hyaluronic acid with cohesive polydensified matrix hyaluronic acid has been well explored in subjects with lighter skin (i.e., Fitzpatrick skin types I, II, and III), further exploration in subjects with Fitzpatrick skin types IV, V, and IV is warranted. The primary purpose of the study was to assess the safety of a cohesive polydensified matrix hyaluronic acid in the correction of nasolabial folds in subjects with Fitzpatrick skin types IV, V and VI, especially assessment of hyperpigmentation, hypopigmentation, and scarring. Effectiveness was also assessed. METHODS: A total of 93 subjects were enrolled in this 24-week investigation at three sites in the United States. All were injected bilaterally for nasolabial fold correction with cohesive polydensified matrix hyaluronic acid. Assessments included the recording of adverse events; injected volumes; wrinkle severity ratings; and global aesthetic improvement by evaluating investigators, treating investigators, and study subjects. RESULTS: Injection of cohesive polydensified matrix hyaluronic acid for the treatment of nasolabial folds in subjects with Fitzpatrick skin types IV, V, and VI showed no evidence of an association with hypopigmentation, hyperpigmentation, or scarring. Adverse events reported were typical of dermal filler injections with respect to type, rate, duration, and severity. CONCLUSION: Cohesive polydensified matrix hyaluronic acid is a safe and well-tolerated dermal filler for subjects with Fitzpatrick skin types IV, V, and VI.

Esthetic considerations for ethnic skin.

The initial assessment of ethnic skin needs to be culturally sensitive. A clear discussion about expectations, number of treatment sessions required for a likely result, limitations of a particular cosmetic modality, or product as well as a discussion of the potential side effects must be carefully explained during a consultation. As the skin of color market continues to grow, the long-term cosmetic concerns of the individuals that comprise this market should be comprehensively evaluated. Esthetic considerations for ethnic skin presently include cosmeceuticals, laser treatments, injections with Botox, chemical peels, Restylane, Sculptra, fitness, hair loss, and sun protection.