Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% gel for moderate-to-severe acne: Efficacy and safety results from two randomized phase 3 trials.

BACKGROUND: A three-pronged acne treatment approach-combining an antibiotic, antibacterial agent, and retinoid-may provide greater efficacy than single/double treatments. Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (IDP-126) is the first fixed-dose triple-combination in development for acne. OBJECTIVE: To confirm efficacy, safety, and tolerability of IDP-126 gel in acne treatment. METHODS: Two phase 3, double-blind, 12-week studies randomized participants aged ≥9 years with moderate-to-severe acne (N = 183; N = 180) 2:1 to once-daily IDP-126 or vehicle gel. Co-primary endpoints comprised participants achieving ≥2-grade reduction from baseline in Evaluator's Global Severity Score (EGSS) and clear/almost clear skin (treatment success) and change from baseline in inflammatory/noninflammatory lesion counts. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: At week 12, 49.6% and 50.5% of participants achieved treatment success with IDP-126 versus 24.9% and 20.5% with vehicle (P < .01, both). IDP-126 also provided significantly greater reductions in inflammatory/noninflammatory lesions versus vehicle (least-squares mean percent range: 72.7% to 80.1% vs 47.6% to 59.6%; P < .001, all). Most TEAEs were of mild-moderate severity. LIMITATIONS: Inter-observer bias/variation in acne severity ratings, limited treatment duration, and population differences that may not generalize to real-world populations. CONCLUSION: The innovative fixed-dose, triple-combination IDP-126 gel was efficacious and well tolerated in 2 clinical studies of participants with moderate-to-severe acne.

Noninvasive Hands-free Bipolar Radiofrequency Facial Remodeling Device for the Improvement of Skin Appearance.

BACKGROUND: Aging is a multifactorial response to genetic preprogramming nuances, sun exposure, and ultraviolet radiation. Recently, there has been a paradigm shift toward minimally invasive rejuvenation. OBJECTIVE: This prospective multicenter study aims to evaluate the efficacy and safety of a novel hands-free bipolar bulk radiofrequency (RF) device in terms of improvement in skin appearance. PATIENTS AND METHODS: This multicenter prospective study enrolled subjects aged 35 to 75 years with visible signs of aging. The primary objective was to evaluate skin appearance pretreatment and at 1, 3, and 6 months after the final treatment. Each patient received 3 total treatments to the chin and cheeks using the hands-free RF device spaced 2 weeks apart. RESULTS: In total, data from 87 patients were assessed from 6 treatment sites. The average age was 54 years (range 35-75 years). Most patients were female (97%), and Fitzpatrick skin types I to V were represented. Overall, patients found the procedures to be relatively pain-free, and both patients and investigators felt they noted some improvement in their skin appearance. Histological sections demonstrated an increase in collagen or elastic fibers within the papillary dermis. CONCLUSION: This study supports the use of this novel noninvasive hands-free bipolar facial remodeling device for the improvement of skin appearance.

Development and Validation of the Patient-Reported Submental Fat Rating Scale and the Patient-Reported Submental Fat Impact Scale.

BACKGROUND: No validated assessment tools are available to evaluate patient-reported outcomes specifically related to submental fat (SMF). OBJECTIVE: To develop and validate scales measuring the severity (Patient-Reported SMF Rating Scale [PR-SMFRS]) and psychological impact (Patient-Reported SMF Impact Scale [PR-SMFIS]) of SMF. MATERIALS AND METHODS: A literature review, content validation interviews (concept elicitation [n = 29] and cognitive debriefing [n = 15]) in adults with SMF, and expert interviews (n = 3) were conducted to develop the PR-SMFRS and PR-SMFIS. Psychometric validity (acceptability, reliability, and validity) for the PR-SMFRS and PR-SMFIS was assessed using data from 1 phase 2 and 5 phase 3 ATX-101 studies in patients with excess SMF. RESULTS: The PR-SMFRS was constructed as a single-item, 5-point rating of the SMF amount/size. The PR-SMFIS was constructed as a 6-item scale, with an 11-point numeric rating for each item. Both scales demonstrated acceptable psychometric properties (test-retest reliability and internal consistency). The anchor-based minimally important difference analysis suggests a 1-point improvement on the PR-SMFRS (scale of 0‒4) and a 3-point improvement on the PR-SMFIS (scale of 0‒10) represent clinically meaningful change. CONCLUSION: The PR-SMFRS and PR-SMFIS are reliable, valid instruments for assessing the severity and psychosocial impact, respectively, of SMF and detecting clinically meaningful change with intervention.

The First 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 assessed by the investigator 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 of 20 U prabotulinumtoxinA (4 U/0.1 mL freeze-dried formulation injected into 5 target 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 was evaluated throughout the study. RESULTS: The 352 study patients received a median total dose of 60 U, that is, 3 treatments per year. Fifty-one patients (14.5%) experienced adverse events (AEs) assessed as possibly study drug related; 11.1% experienced study drug-related AEs after the initial treatment. With each RT, progressively lower percentages of patients experienced study drug-related AEs. Six patients (1.7%) experienced study drug-related AEs of special interest: 3 eyelid ptosis (0.9%), 2 speech disorder (0.6%), and 1 blepharospasm (0.3%). Seven patients (2.0%) experienced serious AEs; none were study drug related. Of the 2393 samples tested, 2 patients (0.6%) tested positive for antibotulinum toxin antibodies at a single postbaseline visit. CONCLUSIONS: The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was first established in this early phase II study based on a broad range of outcomes.

CME: Re-examining the Optimal Use of Neuromodulators and the Changing Landscape: A Consensus Panel Update.

Since initial US Food and Drug Administration approval of botulinum toxin type A (BoNT-A) for aesthetic use in 2002, clinical evidence and experience with BoNT-A and understanding of facial anatomy have greatly increased, leading to rapid advances in treatment planning and implementation. BoNT-A use has expanded from the upper face to the midface, lower face, and neck, so that BoNT-A injection is the most common cosmetic procedure worldwide. Trends in facial aesthetics reflect growing patient diversity with respect to age, gender, and ethnicity. In October 2019, a multidisciplinary panel of 6 experts in minimally invasive injectable procedures in the specialties of dermatology and plastic surgery convened at the 2019 American Society for Dermatologic Surgery (ASDS) meeting in Chicago, IL. Their goal was to discuss recent advances in BoNT-A use in facial aesthetics, including implications of the introduction of new agents in light of an evolving patient population. J Drugs Dermatol. 2020;19(4 Suppl 1):s5-15To receive a CME certificate of participation, you should: •Read the entire publication, including the CME information. •Register or log in at www.paradigmmc.com/822 to complete and submit the online posttest and evaluation. Following online completion of the posttest and evaluation, a certificate of participation will be available for download/printing immediately.Erratum published for this article here.

Re-examining the Optimal Use of Neuromodulators and the Changing Landscape: A Consensus Panel Update

Since initial US Food and Drug Administration approval of botulinum toxin type A (BoNT-A) for aesthetic use in 2002, clinical evidence and experience with BoNT-A and understanding of facial anatomy have greatly increased, leading to rapid advances in treatment planning and implementation. BoNT-A use has expanded from the upper face to the midface, lower face, and neck, so that BoNT-A injection is the most common cosmetic procedure worldwide. Trends in facial aesthetics reflect growing patient diversity with respect to age, gender, and ethnicity. In October 2019, a multidisciplinary panel of 6 experts in minimally invasive injectable procedures in the specialties of dermatology and plastic surgery convened at the 2019 American Society for Dermatologic Surgery (ASDS) meeting in Chicago, IL. Their goal was to discuss recent advances in BoNT-A use in facial aesthetics, including implications of the introduction of new agents in light of an evolving patient population. J Drugs Dermatol. 2020;19(4 Suppl 1):s5-15 To receive a CME certificate of participation, you should: •Read the entire publication, including the CME information. •Register or log in at www.paradigmmc.com/822 to complete and submit the online posttest and evaluation. Following online completion of the posttest and evaluation, a certificate of participation will be available for download/printing immediately.

Erratum: Re-examining the Optimal Use of Neuromodulators and the Changing Landscape: A Consensus Panel Update

Correction to the supplement, Re-examining the Optimal Use of Neuromodulators and the Changing Landscape: A Consensus Panel Update (J Drugs Dermatol. 2020; 19:4 Supp 1).

Validated Assessment Scales for Cellulite Dimples on the Buttocks and Thighs in Female Patients.

BACKGROUND: New treatment methods for cellulite require globally accepted scales for aesthetic research and patient evaluation. OBJECTIVE: To develop a set of grading scales for objective assessment of cellulite dimples on female buttocks and thighs and assess their reliability and validity. MATERIALS AND METHODS: Two photonumeric grading scales were created and validated for dimples in the buttocks in female patients: Cellulite Dimples-At Rest, and Cellulite Dimples-Dynamic. Sixteen aesthetic experts rated photographs of 50 women in 2 validation sessions. Responses were analyzed to assess inter-rater and intra-rater reliability. RESULTS: Overall inter-rater reliability and intra-rater reliability were both "almost perfect" (≥0.81, intraclass correlation efficient and weighted kappa) for the At Rest scale. For the Dynamic scale, inter-rater reliability and intra-rater reliability were "substantial" (0.61-0.80). There was a high correlation between the cellulite scales and body mass index, age, weight, and skin laxity assessments. CONCLUSION: Consistent outcomes between raters and by individual raters at 2 time points confirm the reliability of the cellulite dimple grading scales for buttocks and thighs in female patients and suggest they will be a valuable tool for use in research and clinical practice.

Validated Assessment Scales for Skin Laxity on the Posterior Thighs, Buttocks, Anterior Thighs, and Knees in Female Patients.

BACKGROUND: The demand for noninvasive skin-tightening body procedures is increasing. OBJECTIVE: To develop a set of grading scales for the objective assessment of skin laxity and assess their reliability and validity. MATERIALS AND METHODS: Two photonumeric grading scales were created and validated for skin laxity in female patients: Skin Laxity-Posterior Thighs/Buttocks, and Anterior Thighs/Knees. Fifteen aesthetic experts rated photographs of 50 women in 2 validation sessions. Responses were analyzed to assess inter-rater and intra-rater reliability. RESULTS: Overall inter-rater reliability according to intraclass correlation efficient (ICC) 2.1 and weighted kappa was at least "substantial" for both scales in both sessions, and "almost perfect" (≥0.81) for the Anterior Thighs and Knees scale in session 2. Intra-rater reliability was "almost perfect" for both scales (ICC 2.1) and "substantial" to "almost perfect" by weighted kappa. A correlation between the skin laxity scales and body mass index, age, weight, sun exposure, and cellulite severity was observed. CONCLUSION: The skin laxity photonumeric grading scales are valid and reliable instruments for assessing laxity on the posterior thighs and buttocks, and anterior thighs and knees. The scales will be of value for standardizing clinical evaluations and quantifying outcome measurements in research and clinical practice.

Safety and efficacy of hydrogen peroxide topical solution, 40% (w/w), in patients with seborrheic keratoses: Results from 2 identical, randomized, double-blind, placebo-controlled, phase 3 studies (A-101-SEBK-301/302).

BACKGROUND: Approved topical treatments for seborrheic keratoses (SKs) are an unmet need. OBJECTIVE: To evaluate the safety and efficacy of 40% hydrogen peroxide topical solution (HP40) versus vehicle for the treatment of SKs (A-101-SEBK). METHODS: A total of 937 patients with 4 SKs each (≥1 lesion each on the face and on the trunk and/or an extremity) were randomized 1:1 to HP40 or vehicle. At each visit, SKs were graded using the Physician's Lesion Assessment (PLA) scale (0, clear; 1, nearly clear; 2, ≤1 mm thick; and 3, >1 mm thick). After 1 treatment, SKs with a PLA score higher than 0 were re-treated 3 weeks later. RESULTS: At day 106, significantly more patients treated with HP40 than with vehicle achieved a PLA score of 0 on all 4 SKs (study 1, 4% vs 0%; study 2, 8% vs 0% [both P < .01]) and on 3 of 4 SKs (study 1, 13% vs 0%; study 2, 23% vs 0% [both P < .0001]). A higher mean per-patient percentage of SKs were clear (study 1, 25% vs 2%; study 2, 34% vs 1%) and clear or nearly clear (study 1, 47% vs 10%; study 2, 54% vs 5%) with HP40 than with vehicle. Local skin reactions were largely mild and resolved by day 106. LIMITATIONS: The optimal number of treatment sessions was not evaluated. CONCLUSION: Application of HP40 was well tolerated and effective in the removal of SKs.

Global Consensus Guidelines for the Injection of Diluted and Hyperdiluted Calcium Hydroxylapatite for Skin Tightening.

BACKGROUND: Calcium hydroxylapatite (CaHA) is approved to correct moderate-to-severe wrinkles and folds and soft-tissue volume loss in the face and hands. More recently, subdermal injection using diluted CaHA has been used to improve skin laxity. OBJECTIVE: To review evidence for the safe and effective use of diluted CaHA in the face and body and provide best practice recommendations. METHODS: A global panel of expert aesthetic physicians convened to develop consensus-based guidelines for treating laxity and superficial wrinkles using diluted (ratio of 1:1) and hyperdiluted (≥1:2) CaHA. RESULTS: Diluted and hyperdiluted CaHA stimulates targeted neocollagenesis in the injection area to improve laxity and skin quality in the mid- and lower face, neck, décolletage, upper arms, abdomen, upper legs, and buttocks. Treatment can be used as an adjunct to volume augmentation or combined with additional modalities for optimal results. Adverse events are related to the injection and include bruising, swelling, mild pain, and induration. In thinner and darker skin, too-superficial injections of less diluted CaHA can lead to more adverse events. CONCLUSION: This report provides preliminary guidelines for the novel off-label use of CaHA for biostimulation in the face and body. Further trials will provide additional clarity regarding treatment paradigms for optimal outcomes.

Tox Outside the Box: Off-Label Aesthetic Uses of Botulinum Toxin.

*Proceedings from a recent cosmetic dermatology conference, Cosmetic Bootcamp, Aspen, CO.

Human Stem Cell-Derived Skin Progenitors Produce Alpha 2-HS Glycoprotein (Fetuin): A Revolutionary Cosmetic Ingredient.

These studies were designed to determine the effect of stem cell-derived skin lineage precursor secretions on the intrinsic and extrinsic symptoms of human skin aging.
Human stem cells cultivated in balanced conditions were differentiated into skin lineage precursors, and shown to secrete large amounts of fetuin as well as multiple growth factors beneficial for human skin development and maintenance. The cell secretions were incorporated in two simple cosmetic formulations (serum and lotion) and investigated in an IRB-approved 12-week human trial that included 25 subjects in each group. Subjects were examined at 2, 4, 8, and 12 weeks by a dermatologist to evaluate safety, trans-epidermal water loss, wrinkles, firmness, radiance, texture, softness, and overall appearance. A sub-group of subjects from each group consented for biopsies for histological analyses.
Protein analyses in the cell secretions revealed a high concentration of the multifunctional alpha 2-HS glycoprotein (fetuin) along with a multitude of protein factors involved in the development and maintenance of healthy human skin. Clinical investigation demonstrated significant amelioration of the clinical signs of intrinsic and extrinsic skin aging, findings that were confirmed by significant changes in skin morphology, filaggrin, aquaporin 3, and collagen I content.
Our data strongly support our hypothesis that cosmetic application of stem cell-derived skin lineage precursor secretions containing fetuin and growth factors beneficial for human skin development and maintenance, positively influence intrinsic and extrinsic aging.

J Drugs Dermatol. 2016;15(5):583-598.

Efficacy and safety of onabotulinumtoxinA for treating crow's feet lines alone or in combination with glabellar lines: a multicenter, randomized, controlled trial.

BACKGROUND: This was the second study in a Phase 3 program treating crow's feet lines (CFL) with onabotulinumtoxinA. OBJECTIVE: To evaluate the efficacy and safety of onabotulinumtoxinA treatment of CFL alone or with glabellar lines (GL). METHODS: This multicenter, double-blind, placebo-controlled, repeat treatment, 7-month study randomized subjects with moderate-to-severe CFL and GL (maximum contraction) to onabotulinumtoxinA 44 U (CFL: 24 U, GL: 20 U; n = 305), onabotulinumtoxinA 24 U (CFL: 24 U, GL: placebo; n = 306), or placebo (n = 306). Coprimary end points were investigator-assessed and subject-assessed proportion of subjects achieving a CFL Facial Wrinkle Scale Grade of 0 or 1 (maximum smile; Day 30, Cycle 1). Additional efficacy end points and safety/adverse events (AEs) were evaluated. RESULTS: All primary and secondary end points were achieved; statistically significant differences favored onabotulinumtoxinA (p < .001, all comparisons vs placebo). Investigator and subject responder rates were: CFL, 54.9% and 45.8%; CFL + GL, 59.0% and 48.5%; and placebo, 3.3% (both), respectively. Responder rates on other end points also significantly favored onabotulinumtoxinA treatments. Most AEs were mild or moderate. Two subjects discontinued: 1 serious AE unrelated to treatment (myocardial infarction) and 1 treatment-related AE (injection site pain). CONCLUSION: OnabotulinumtoxinA was effective and well tolerated for treating moderate-to-severe CFL alone or in combination with GL.

Pilot, Multicenter, Open-Label Evaluation of Safety, Tolerability and Efficacy of a Novel, Topical Multipotent Growth Factor Formulation for the Periorbital Region.

BACKGROUND: This multicenter, open-label pilot study evaluated safety, efficacy and tolerability of a topical formulation containing a multipotent growth factor resignaling complex (MRCx), when applied to infraorbital and lateral canthal skin. METHODS: Thirty-nine female subjects with mean age of 56.8 years who had periorbital lines and wrinkles, uneven skin texture, puffiness, and lack of skin firmness were enrolled, and 38 completed the study. All subjects applied the multipotent growth factor formulation bilaterally to the periorbital area, twice daily for 60 days. Efficacy and treatment-related adverse events were evaluated at Baseline and days 14, 30, and 60. Investigators rated the periorbital areas based on 10-point scales. RESULTS: Subjects' self-reported compliance with treatment was greater than 99% throughout the study. At day 60, all subjects had improvement in infraorbital brightness (≥ 2 points), moistness (≥ 2 points), wrinkles (≥ 1 point), sallowness (≥ 1 point), crepiness (≥ 1 point), smooth texture (≥ 1 point), skin tightness (≥ 1 point), and skin tone (≥ 1 point). Investigator-rated assessments showed ≥ 1-point improvement for lateral canthal wrinkles, dyschromia/mottled pigmentation, skin tone, overall brightness, and moistness. Investigator-rated scoring on the Global Aesthetic Improvement Scale (GAIS) demonstrated that 67.6% of subjects were much improved/improved at day 14, and 63.1% remained improved at day 60. Overall, 76.2% and 79.0% of subjects were very pleased/pleased/mostly pleased with the appearance of their infraorbital and lateral canthal areas at day 60. Adverse events comprised one case of mild canthal erythema, and one case of mild eye irritation, both of which were respectively resolved. CONCLUSIONS: This pilot study demonstrated that the topical multipotent growth factor formulation was safe, effective and well tolerated for periorbital skin rejuvenation.

Triple Combination Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% for Acne: Efficacy and Safety from a Pooled Phase 3 Analysis.

INTRODUCTION: A three-pronged approach to acne treatment combining an antibiotic, antimicrobial, and retinoid may be more efficacious than single/double treatments while potentially reducing antibiotic resistance. This study evaluated the efficacy and safety of the first fixed-dose, triple-combination topical acne product, clindamycin 1.2%/adapalene 0.15%/benzoyl peroxide (BPO) 3.1% gel (CAB) using pooled phase 3 data. METHODS: In two identical phase 3 (N = 183; N = 180), double-blind, 12-week studies, participants aged ≥ 9 years with moderate-to-severe acne were randomized 2:1 to receive once-daily CAB or vehicle gel. Endpoints included ≥ 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin (treatment success) and least-squares mean percent change from baseline in acne lesion counts. Treatment-emergent adverse events (TEAEs) and cutaneous safety/tolerability were evaluated. RESULTS: At week 12, 50.0% of participants achieved treatment success with CAB versus 22.6% with vehicle gel (P < 0.001). CAB resulted in > 70% reductions in inflammatory and noninflammatory lesions at week 12 (77.9% and 73.0%, respectively), which were significantly greater than vehicle (57.9% and 48.2%; P < 0.001, both). Most TEAEs were of mild-moderate severity, and < 3% of CAB-treated participants discontinued study/treatment because of AEs. Transient increases from baseline in scaling, erythema, itching, burning, and stinging were observed with CAB, but resolved back to or near baseline values by week 12. CONCLUSIONS: The innovative fixed-dose, triple-combination clindamycin phosphate 1.2%/adapalene 0.15%/BPO 3.1% gel was efficacious and well tolerated in children, adolescents, and adults with moderate-to-severe acne. Half of participants achieved clear/almost clear skin by 12 weeks, rates not previously seen in clinical studies of other topical acne products. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04214639 and NCT04214652.