Triple-combination clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel for moderate-to-severe acne in children and adolescents: Randomized phase 2 study.

BACKGROUND/OBJECTIVES: Topical clindamycin phosphate 1.2%/benzoyl peroxide 3.1%/adapalene 0.15% gel (IDP-126) is the first fixed-dose triple-combination formulation in development for acne. This post hoc analysis investigated efficacy and safety of IDP-126 in children and adolescents with moderate-to-severe acne. METHODS: In a randomized, double-blind phase 2 study (NCT03170388), participants ≥9 years of age with moderate-to-severe acne were eligible for randomization (1:1:1:1:1) to once-daily IDP-126, one of three dyad combination gels, or vehicle gel for 12 weeks. This post hoc analysis of pediatric participants (n = 394) included children and adolescents up to 17 years of age. Assessments included treatment success, inflammatory/noninflammatory lesion counts, Acne-Specific Quality of Life (Acne-QoL) questionnaire, treatment-emergent adverse events (TEAEs), and cutaneous safety/tolerability. RESULTS: At Week 12, treatment success rates were significantly greater with IDP-126 (55.8%) than with vehicle (5.7%; p < .001) or any of the dyad combinations (range: 30.8%-33.9%; p < .01, all). Lesion reductions with IDP-126 were also significantly greater than with vehicle (inflammatory: 78.3% vs. 45.1%; noninflammatory: 70.0% vs. 37.6%; p < .001, both) and 9.2%-16.6% greater than with any of the dyad combinations. Increases (improvements) from baseline in Acne-QoL domain scores were generally greater with IDP-126 than in any other treatment group. The most common treatment-related TEAEs across treatment groups were application site pain and dryness. Most treatment-related TEAEs were of mild-to-moderate severity. CONCLUSION: IDP-126 gel-a novel fixed-dose, triple-combination topical formulation for acne-demonstrated superior efficacy to vehicle and three dyad component gels and was well tolerated in children and adolescents with moderate-to-severe acne.

Oxymetazoline and Energy-Based Therapy in Patients with Rosacea: Evaluation of the Safety and Tolerability in an Open-Label, Interventional Study.

BACKGROUND AND OBJECTIVES: The objectives of this study were to evaluate the safety, tolerability, and efficacy of oxymetazoline hydrochloride cream, 1% (oxymetazoline) when used as an adjunctive treatment with energy-based therapy for patients with moderate to severe facial erythema associated with rosacea. STUDY DESIGN/MATERIALS AND METHODS: In this Phase 4, multicenter, interventional, open-label study, eligible patients received one of four energy-based therapies (potassium titanyl phosphate laser, intense pulsed light therapy, pulsed-dye laser Vbeam Perfecta, or pulsed-dye laser Cynergy) on day 1 and day 29 and once-daily application of oxymetazoline on days 3 through 27 and days 31 through 56. Improvement from baseline in Clinician Erythema Assessment (CEA) score, patient satisfaction measures, incidence of treatment-emergent adverse events (TEAEs), and worsening from baseline on dermal tolerability assessments and the Clinician Telangiectasia Assessment (CTA) were assessed. Data were summarized using descriptive statistics. RESULTS: A total of 46 patients (mean age, 51.1 years; 78.3% female) enrolled in this study. Similar numbers of patients received each of the energy-based therapies in addition to oxymetazoline. All patients demonstrated an improvement from baseline in CEA during the study with 39 of 43 evaluable patients (90.7%) demonstrating an improvement 6 hours posttreatment on day 56. Most patients were satisfied or very satisfied with treatment at the end of the study. All TEAEs were mild or moderate in severity. Some patients experienced worsening in dermal tolerability assessment symptoms (range: 4-21 patients; 8.7-45.7%). Worsening in CEA and CTA were each reported by three patients (6.5%) at any time during the study. CONCLUSIONS: Treatment with oxymetazoline as adjunctive therapy with energy-based therapy was safe, well tolerated, and reduced facial erythema in patients with moderate to severe persistent facial erythema associated with rosacea. Lasers Surg. Med. © 2020 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Tazarotene 0.045% Lotion for Moderate-to-Severe Acne Patients: Pooled Phase 3 Analysis by Age and Sex.

BACKGROUND: Two identical phase 3 trials (NCT03168321 and NCT03168334) and pooled post hoc analyses have established efficacy and safety of a polymeric tazarotene 0.045% lotion formulation in patients with moderate-to-severe acne. Presented here are post hoc analyses that further examine efficacy and safety of tazarotene 0.045% lotion by age and sex. METHODS: Patients aged ≥ 9 years with moderate-to-severe acne (score 3 or 4 on the Evaluator's Global Severity Score [EGSS]) were equally randomized to once-daily tazarotene 0.045% lotion or vehicle lotion for 12 weeks. Efficacy outcomes included inflammatory/noninflammatory lesion counts and treatment success (proportion of participants achieving ≥ 2-grade reduction from baseline in EGSS and score of 0 [clear] or 1 [almost clear]). Adolescent and adult females (n=1,013) and males (n=529) were subdivided into 3 age groups: 13­19, 20­29, and ≥30 years. RESULTS: At week 12, large least-squares mean percent reductions in inflammatory and noninflammatory lesions were observed across all 3 tazarotene-treated age groups in males and females (range, -50.2% to -64.8%). Treatment success rates ranged from 23.6% to 38.4%. Across all efficacy assessments, significant differences between tazarotene and vehicle (P<0.05) were generally observed in the younger male and female participants (13­19 and 20­29). No notable age-related patterns were found for safety outcomes, though tazarotene-treated males of all age groups reported fewer adverse events than females. CONCLUSIONS: Tazarotene 0.045% lotion is efficacious and well tolerated in female and male adolescents and adults with moderate-to-severe acne. J Drugs Dermatol. 2021;20(6):608-615. doi:10.36849/JDD.6070.

Fixed-Combination Halobetasol Propionate/Tazarotene Lotion for Psoriasis in Patients With 3%-5% Affected Body Surface Area.

INTRODUCTION: Patients with psoriasis and low body surface area (BSA) involvement often experience substantially reduced quality of life and may be candidates for topical therapies. Fixed-combination halobetasol propionate (0.01%) and tazarotene (0.045%) lotion (HP/TAZ) vs vehicle lotion was evaluated in participants with 3% to 5% BSA involvement. METHODS: In two phase 3, multicenter, double-blind, vehicle-controlled, 8-week studies (ClinicalTrial.gov identifiers: NCT02462070/NCT02462122), adults with moderate/severe investigator’s global assessment (IGA) score were randomized 2:1 to once-daily HP/TAZ or vehicle. Pooled post hoc analyses included participants with baseline BSA involvement of 3% to 5%. Measures included treatment success (≥2-grade IGA reduction, clear/almost clear score), reduction in affected BSA, and clinically meaningful improvement (reduction) of ≥4 points on dermatology life quality index (DLQI). RESULTS: Of 418 participants, 232 had baseline BSA involvement of 3% to 5% (HP/TAZ, n=149; vehicle, n=83). At week 8, 42.7% of HP/TAZ-treated participants achieved treatment success, compared with 11.4% of vehicle-treated participants (P< .001). Participants experienced significantly greater reductions in affected BSA at week 8 with HP/TAZ (-36.0%) vs vehicle (-1.6%; P< .001). Larger proportions experienced clinically meaningful DLQI improvements at week 8 with HP/TAZ (64.2%) vs vehicle (47.4%; P< .05). More participants achieved a ≥2-grade improvement in plaque elevation and scaling with HP/TAZ vs vehicle (each comparison, P< .001). Serious adverse events and discontinuations due to treatment-emergent adverse events were rare. CONCLUSIONS: In participants with plaque psoriasis and BSA involvement of 3% to 5%, HP/TAZ provided significantly improved effectiveness after 8 treatment weeks vs vehicle lotion, with clinically meaningful improvements in quality of life. J Drugs Dermatol. 2021;20(8):829-836. doi:10.36849/JDD.6217.

New Polymeric Once-Daily Tazarotene 0.045% Lotion Formulation for Moderate-to-Severe Acne: Pooled Phase 3 Pediatric Analysis.

BACKGROUND: Acne vulgaris affects approximately 85% of adolescents. Topical tazarotene is efficacious and safe for acne treatment but irritation limits its use. The objective was to evaluate efficacy, safety, and tolerability of a new tazarotene 0.045% lotion formulation in patients aged 10-13 and 14-17 years with moderate-to-severe acne. METHODS: In two phase 3, double-blind, vehicle-controlled 12-week studies, patients with moderate-to-severe acne (N=1,614) were randomized (1:1) to receive tazarotene 0.045% lotion or vehicle once-daily. Efficacy assessments included changes from baseline in inflammatory/noninflammatory lesions and treatment success (≥2-grade reduction in Evaluator's Global Severity Score [EGSS] and a clear/almost clear score). Quality of life (QoL) and adverse events (AEs) were also assessed. RESULTS: Patients aged 10-13 years (n=136) and 14-17 years (n=548) were pooled. At week 12, mean percent reductions in inflammatory and noninflammatory lesion counts were significantly greater with tazarotene versus vehicle in both age groups (least-squares mean inflammatory 10-13 years: -55.6 vs -37.0%; 14-17 years: -53.3 vs -41.2%; noninflammatory 10-13 years: -47.7 vs -28.2%; 14-17 years: -52.7 vs -32.9%; P<0.01 all). More patients achieved treatment success with tazarotene versus vehicle in both age groups (P<0.05, both). There were no significant differences between tazarotene-treated age groups in lesion counts or treatment success. Acne-QoL scores at week 12 in both age groups were numerically improved in most domains with tazarotene 0.045% lotion versus vehicle. Most treatment-emergent AEs with tazarotene or vehicle were of mild or moderate severity in both age groups. CONCLUSIONS: Tazarotene 0.045% lotion was efficacious and well tolerated in pediatric patients with moderate-to-severe acne. J Drugs Dermatol. 2020;19(6): doi:10.36849/JDD.2020.4959.

Novel Polymeric Lotion Formulation of Once-Daily Tazarotene (0.045%) for Moderate-to-Severe Acne: Pooled Phase 3 Analysis.

Background: As current tazarotene formulations indicated for acne (0.1%) can cause irritation, a new tazarotene 0.045% lotion formu-lation was developed using polymeric emulsion technology. The objective was to assess efficacy, safety, and tolerability of tazarotene 0.045% lotion in patients with moderate-to-severe acne in a pooled analysis of data from two identical phase 3, double-blind, random-ized, vehicle-controlled 12-week clinical studies. Methods: Patients aged ≥9 years with moderate-to-severe acne were randomized (1:1) to tazarotene 0.045% lotion or vehicle lotion applied once daily. Inflammatory and noninflammatory lesion counts and Evaluator's Global Severity Score (EGSS) were assessed. Treatment success was defined as a ≥2-grade improvement in EGSS and a score of 'clear'/'almost clear'. Adverse events (AEs) and cutaneous safety and tolerability were also assessed. Results: In total, 1614 patients (mean age: 20.5 years) were randomized to tazarotene 0.045% lotion (n=799) or vehicle (n=815). At week 12, tazarotene 0.045% lotion demonstrated statistically significant superiority versus vehicle in reducing inflammatory and non-inflammatory lesion counts (least-squares mean percent changes from baseline: inflammatory, -57.9% vs -47.8% [P<0.001]; noninflam-matory, -56.0% vs -42.0% [P<0.001]). Treatment success at week 12 was also greater with tazarotene 0.045% lotion versus vehicle (30.4% vs 17.9%; P<0.001). The most frequent treatment-emergent AEs related to tazarotene treatment were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). Conclusions: The new tazarotene 0.045% lotion formulated with polymeric emulsion technology demonstrated statistically signifi-cantly superior efficacy versus vehicle and was well tolerated in pediatric and adult patients with moderate-to-severe acne in this pooled analysis of 2 vehicle-controlled phase 3 studies. J Drugs Dermatol. 2020;19(3):272-279. doi:10.36849/JDD.2020.4869.

Tazarotene 0.045% Lotion for Once-Daily Treatment of Moderate-to-Severe Acne Vulgaris: Results from Two Phase 3 Trials

BACKGROUND: Tazarotene has been extensively studied in clinical trials and is widely used to treat acne vulgaris (acne), with data suggesting that is one of the most potent topical retinoids. Irritation from the cream, foam, and gel formulations has limited its use in clinical practice. OBJECTIVE: To assess the efficacy, safety, and tolerability of a unique tazarotene 0.045% lotion formulation based on polymeric emulsion technology in subjects with moderate or severe acne. Methods: A total of 1614 subjects, 9 years and older were randomized to receive tazarotene 0.045% lotion or vehicle in two identical double-blind, randomized, vehicle-controlled 12-week studies evaluating safety and efficacy (inflammatory [papules and pustules] and noninflammatory [comedonal] lesion counts and using Evaluator Global Severity Scores [EGSS]). Treatment success was defined as at least a 2-grade improvement in EGSS and 'clear'/'almost clear' and efficacy assessed through reduction in lesion counts. In addition, patients completed a validated Acne-Specific Quality of Life (Acne-QoL) questionnaire. Safety, adverse events (AEs), and cutaneous tolerability were assessed throughout. RESULTS: Tazarotene 0.045% lotion demonstrated statistically significant superiority to vehicle in reducing inflammatory and noninflammatory lesion counts at week 12. Mean percent reductions in inflammatory and noninflammatory lesions were 55.5% and 51.4% (Study 1, both P<0.001 versus vehicle [45.7% and 41.5%, respectively]) and 59.5% and 60.0% (Study 2, both P<0.001 versus vehicle [49.0% and 41.6%, respectively]), with tazarotene 0.045% lotion at week 12. Treatment success was achieved by 25.5% (Study 1) and 29.6% (Study 2) of subjects treated with tazarotene 0.045% lotion (both P<0.001 versus vehicle [13.0% and 17.3%, respectively]). Improvements in QoL domain scores were consistently greater with tazarotene. Tazarotene 0.045% lotion was well-tolerated. The most common treatment-related AEs were application site pain (5.3%), dryness (3.6%), and exfoliation (2.1%). CONCLUSION: Tazarotene 0.045% lotion provides statistically significant greater efficacy than vehicle in terms of lesion reduction and treatment success, with a highly favorable safety and tolerability profile in moderate-to-severe acne patients. JJ Drugs Dermatol. 2020;19(1):70-77. doi:10.36849/JDD.2020.3977

A Phase 2, Multicenter, Double-Blind, Randomized, Vehicle-Controlled Clinical Study to Compare the Safety and Efficacy of a Novel Tazarotene 0.045% Lotion and Tazarotene 0.1% Cream in the Treatment of Moderate-to-Severe Acne Vulgaris

Background: Tazarotene has been extensively studied in clinical trials and is widely used to treat acne vulgaris (acne). Irritation potential has limited its use. Objective: To compare efficacy, safety, and tolerability of a novel formulation tazarotene 0.045% lotion based on polymeric emulsion technology, and tazarotene 0.1% cream in patients with moderate-to-severe acne. Methods: A total of 210 patients, 12 years and older were randomized to receive tazarotene 0.045% lotion, tazarotene 0.1% cream, or respective vehicle in double-blind, randomized, vehicle-controlled, 12-week study evaluating safety and efficacy (inflammatory and noninflammatory lesion counts and using Evaluator Global Severity Scores [EGSS]). In addition, patients completed a patient satisfaction survey (PSS), and acne-specific quality of life (QoL) questionnaire. Safety and cutaneous tolerability were assessed throughout. Results: A novel tazarotene 0.045% lotion demonstrated statistically significant superiority to vehicle in reducing inflammatory and noninflammatory lesion counts (P=.006 and P<.001) and clearly more effective in treatment success at week 12. In addition, at less than half the concentration, tazarotene 0.045% lotion was numerically more effective than tazarotene 0.1% cream. Mean percent reductions in inflammatory and noninflammatory lesions were 63.8% and 56.9%, compared with 60.0% and 54.1% with tazarotene 0.1% cream at week 12. Treatment success assessed by the investigator or patients' self-assessment was also numerically greater with tazarotene 0.045% lotion. There were no significant differences in patient satisfaction or QoL between the two active treatments. Both were well-tolerated, however, there were more treatment-related adverse events with tazarotene 0.1% cream (5.6% versus 2.9%); most common being application site pain. Limitations: This study was primarily designed to direct the phase 3 program and some of the results are post hoc analyses. Conclusions: A novel tazarotene 0.045% lotion provides statistically significant greater efficacy than vehicle in terms of lesion reduction, and numerically better treatment success than tazarotene 0.1% cream; with a highly favorable safety and tolerability profile in moderate-to-severe acne patients. J Drugs Dermatol. 2019;18(6):542-548.

WITHDRAWN: Efficacy and safety of topical oxymetazoline cream 1.0% for treatment of persistent facial erythema associated with rosacea: findings from the 2 phase 3, 29-day, randomized, controlled REVEAL trials.

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Clinical Experience With Once-Daily Dapsone Gel, 7.5% Monotherapy in Patients With Acne Vulgaris.

BACKGROUND: Dapsone gel, 7.5% is a topical medication approved for acne in patients aged 12 years and older. Clinical trials have demonstrated the safety and efficacy of once-daily dapsone gel, 7.5% in patients with moderate acne. OBJECTIVE: The objective of this report is to describe the clinical course of 8 patients who participated in a 12-week program using once-daily dapsone gel, 7.5% as monotherapy for acne in a real-world clinical setting. MONOTHERAPY PROGRAM: Male and female adults and adolescents with facial acne, representing a broad range of ages, skin phototypes, and ethnicities, and with no prior use of dapsone gel, 7.5% applied the product once daily for 12 weeks as monotherapy for acne. Photographs were taken at baseline and at 12 weeks. The treating dermatologists recorded observations of baseline disease, treatment tolerability, and outcomes. An independent rater assessed Global Acne Assessment Score (GAAS) at baseline and at 12 weeks based on photographs. Patients provided testimonials of their experience with treatment. PROGRAM OUTCOMES: Acne improvement was evident in the photographs of the 8 patients. Changes in GAAS at week 12 of treatment, as assessed by an independent rater, ranged from 1- to 3-grade improvement from baseline. CONCLUSION: Photographs, dermatologist reports, and patient commentary in an office-based practice demonstrated that 12 weeks of treatment with only topical dapsone gel, 7.5%, applied once daily, was effective and well tolerated as a stand-alone treatment in 8 patients with facial acne vulgaris, with results that are consistent with the phase 3 pivotal trials. J Drugs Dermatol. 2018;17(6):602-608.

Pivotal Trial of the Efficacy and Safety of Oxymetazoline Cream 1.0% for the Treatment of Persistent Facial Erythema Associated With Rosacea: Findings from the Second REVEAL Trial.

Rosacea is a chronic dermatologic condition with limited treatment options, particularly for persistent erythema. This pivotal phase 3 study evaluated oxymetazoline, an a1A-adrenoceptor agonist, for the treatment of moderate to severe persistent erythema of rosacea. Eligible patients were randomly assigned 1:1 to receive oxymetazoline cream 1.0% or vehicle applied topically to the face once daily for 29 days. The primary efficacy outcome was ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment for rosacea facial redness (SSA) (composite success) at 3, 6, 9, and 12 hours postdose on day 29. Digital image analysis of rosacea facial erythema was evaluated as a secondary efficacy outcome measure. Safety assessments included treatment-emergent adverse events (TEAEs) and dermal tolerability. Patients were followed for 28 days posttreatment to assess worsening of erythema (1-grade increase in severity from baseline on composite CEA/SSA in patients with moderate erythema at baseline; rebound effect). The study included 445 patients (mean age: 50.3 years; 78.7% female); most had moderate erythema at baseline (84.0% on CEA; 91.5% on SSA). The proportion of patients achieving the primary efficacy outcome was significantly greater with oxymetazoline versus vehicle (P=0.001). Similar results favoring oxymetazoline over vehicle were observed for the individual CEA and SSA scores (P less than 0.001 and P=0.011, respectively). Median reduction in rosacea facial erythema on day 29 as assessed by digital image analysis also favored oxymetazoline over vehicle (P less than 0.001). Safety results were similar between oxymetazoline and vehicle; discontinuations due to TEAEs were low (2.7% vs 0.5%). Following cessation of treatment, 2 (1.2%) patients in the oxymetazoline group and no patient in the vehicle group had rebound effect compared with their day 1 baseline score. Topical oxymetazoline applied to the face once daily for 29 days was effective, safe, and well tolerated in the treatment of moderate to severe persistent facial erythema of rosacea.

J Drugs Dermatol. 2018;17(3):290-298.

Safety and Efficacy of a Fixed Combination Halobetasol and Tazarotene Lotion in the Treatment of Moderate-to-Severe Plaque Psoriasis: A Pooled Analysis of Two Phase 3 Studies.

BACKGROUND: Topical corticosteroids (TCS) are the mainstay of psoriasis treatment. Safety concerns may limit use. Combination with tazarotene may optimize efficacy and minimize safety and tolerability concerns. OBJECTIVE: Investigate safety and efficacy of halobetasol propionate 0.01%/tazarotene 0.045% (HP/TAZ) lotion in moderate-to-severe plaque psoriasis. METHODS: Two multicenter, randomized, double-blind, vehicle-controlled phase 3 studies (N=418). Subjects randomized (2:1) to HP/TAZ lotion or vehicle once-daily for 8 weeks, 4-week follow-up. Primary efficacy assessment: treatment success (at least a 2-grade improvement from baseline in IGA score and 'clear' or 'almost clear'). Safety and treatment emergent AEs evaluated throughout. RESULTS: HP/TAZ lotion demonstrated statistically significant superiority over vehicle as early as week 2 (P equals 0.002). By week 8, 40.6% of subjects were treatment successes compared with 9.9% on vehicle (P less than 0.001). A third of subjects remained treatment successes post-treatment. HP/TAZ lotion was also superior in reducing psoriasis signs and symptoms, and Body Surface Area (BSA) involvement. Most frequently reported treatment related AEs were contact dermatitis (6.3%), application site pain (2.6%), and pruritus (2.2%). LIMITATIONS: No data were collected beyond the 4-week follow-up. CONCLUSIONS: HP/TAZ lotion provides synergistic efficacy that is both rapid and sustained, with good tolerability and safety over 8 weeks use. J Drugs Dermatol. 2018;17(8):855-861.

Clinically Relevant Reduction in Persistent Facial Erythema of Rosacea on the First Day of Treatment With Oxymetazoline Cream 1.0.

BACKGROUND: Persistent facial erythema is a clinically challenging feature of rosacea. OBJECTIVE: To evaluate persistent erythema reduction on the first day of treatment from pooled data from two pivotal trials of topical oxymetazoline cream 1.0% (oxymetazoline) in persistent facial erythema of rosacea. METHODS: In two identically designed, phase 3, multicenter trials, adults with moderate to severe persistent facial erythema of rosacea (Clinician Erythema Assessment [CEA] grade ≥3 and Subject Self-Assessment [SSA] grade ≥3) were randomized 1:1 to once-daily topical oxymetazoline or vehicle; the primary efficacy endpoint was ≥2-grade composite CEA and SSA improvement from baseline on day 29. This post hoc analysis evaluated the proportion of patients achieving ≥1-grade composite and individual CEA and SSA improvement at 1, 3, 6, 9, and 12 hours postdose on day 1 (N=885). RESULTS: Significantly more patients achieved ≥1-grade composite and individual CEA and SSA improvement with the first application of oxymetazoline than with vehicle (P less than 0.001) at all postdose time points, beginning with hour 1. Day 1 safety assessments were similar between treatments. LIMITATIONS: Short-term, post hoc analysis. CONCLUSIONS: A ≥1-grade improvement in persistent erythema achieved after the first dose of once-daily topical oxymetazoline demonstrated clinically meaningful improvement from the beginning of therapy. J Drugs Dermatol. 2018;17(6):621-626.

Short-pulsed laser for the treatment of tattoos, pigmented lesions, scars and rejuvenation.

This review describes the use of picosecond lasers for the treatment of tattoos, pigmented lesions, scars, and their use in rejuvenation. These devices have delivered enhanced efficacy for the treatment of tattoos and pigmented lesions when compared to the older 40-50 nanosecond devices. The fractional delivery with the picosecond devices have opened up a new method of rejuvenation for photodamaged skin and the treatment of scars. The delivery of these high-energy short pulses have created zones of injury in the skin referred to as areas of laser-induced optical breakdown. These areas of damage appear to produce cytokines and chemokines which result in epidermal and dermal repair and remodeling. The dual use of these devices with the flat and the fractional optics have made these devices useful in many ways that have been unanticipated.

The histology of skin treated with a picosecond alexandrite laser and a fractional lens array.

BACKGROUND AND OBJECTIVES: The treatment of acne scars and wrinkles with a picosecond Alexandrite laser was recently FDA cleared. In 2014 we presented our initial histologic findings with this device on in vivo and ex vivo skin. This current study expands on the 2014 pilot study with an investigation of different energy settings using histology and the confocal microscope to describe the changes observed in the skin. MATERIALS AND METHODS: We used a 755 nm picosecond Alexandrite laser with a fractional optic with three different energy settings to treat in vivo. After treatment, the patients and skin samples were also evaluated with a confocal microscope followed by biopsies which were evaluated histologically. RESULTS: Histology revealed unique intra-epidermal cavities. The number, density, and the size of these cavities were dependent on the melanin index and delivered energy when evaluated with histopathology and the confocal microscope. These localized zones of injury appear to form microscopic epidermal injury zones which are exfoliated over a 3-week period. CONCLUSIONS: These intra-epidermal cavities result from areas of laser-induced optical breakdown (LIOB). This injury is most consistent with a localized plasma formation in the epidermis initiated by the melanin absorption of the high energy picosecond light. It appears that treatments with this device and optic result in improvements in dyspigmentation and acne scars with new collagen, elastic tissue, and mucin. The production of this LIOB could directly stimulate an epidermal repair mechanism that results in these clinical findings. Lasers Surg. Med. 48:646-652, 2016. © 2016 Wiley Periodicals, Inc.

Comparison of the Cutaneous Thermal Signatures Over Twenty-Four Hours With a Picosecond Alexandrite Laser Using a Flat or Fractional Optic.

INTRODUCTION: This study explored immediate heat signatures with different passing techniques and the delayed thermal data points with the picosecond Alexandrite laser with the 6mm at and fractional optic during and after treatment. We sought to clarify the im- mediate effects of heating and understand the thermal and short term clinical difference when using these optics. RESULTS: There were no immediate differences or a signi cant temperature rise with different passing techniques using the at or the fractional optic. However, after treatments a signi cant temperature elevation over 24 hours with manageable erythema was noted with the fractional optic. Only faint redness was appreciated with the at optic. CONCLUSION: The different passing methods with these optics did not result in a significant thermal change. However, the fractional optic produces a localized area of epidermal necrosis which results in a significant clinical and a delayed thermal effect. With multiple treatments over time, collagen, elastic tissue, and mucin is produced resulting in improvement of acne scars and photo-damaged skin. This process suggests that a well-placed epidermal injury can stimulate an inflammatory cascade with dermal remodeling. J Drugs Dermatol. 2016;15(11):1347-1352..

A Randomized, Double-Blind Trial to Investigate the Equivalence of IncobotulinumtoxinA and OnabotulinumtoxinA for Glabellar Frown Lines.

BACKGROUND: IncobotulinumtoxinA and onabotulinumtoxinA are indicated for the temporary improvement in the appearance of glabellar frown lines (GFL). This is the first randomized direct comparator study to date, at the Food and Drug Administration-recommended dose of 20 units (U), for the treatment of GFL. OBJECTIVE: To investigate the dose equivalence of incobotulinumtoxinA (20 U) and onabotulinumtoxinA (20 U) for the treatment of moderate-to-severe GFL. MATERIALS AND METHODS: Prospective, randomized (1:1), double-blinded, parallel-group study in 250 females (18-50 years), employing a single treatment with incobotulinumtoxinA or onabotulinumtoxinA, followed by a 4-month observational period. RESULTS: At the primary efficacy endpoint (1 month after treatment), incobotulinumtoxinA was equivalent to onabotulinumtoxinA in the treatment of GFL at the 20 U dose within the prespecified ± 15% margin of equivalence. Efficacy remained similar between treatment groups through 4 months after treatment as assessed by the independent masked panel and the masked treating physicians. Patient satisfaction ratings were similar between groups and favorable (>90%) throughout. Both treatments were well tolerated. CONCLUSION: Equivalence was demonstrated at the primary endpoint between incobotulinumtoxinA and onabotulinumtoxinA in the treatment of GFL at the 20 U dose at 1 month. Similar efficacy and tolerability profiles were observed through 4 months after treatment.

A Controlled Comparison Study of Topical Fluourouracil 5% Cream Pre-Treatment of Aminolevulinic Acid/Photodynamic Therapy for Actinic Keratosis.

INTRODUCTION: Topical Fluorouracil 5% cream (5-FU) and 20% aminolevulinic acid (ALA)/ photodynamic therapy (PDT) are both FDA approved for the treatment of Actinic Keratosis (AK). We have studied the use of these 2 agents alone and in a sequential manner. We have also used a 5-FU re-challenge 3 months after treatment to highlight the efficacy of these treatments. METHODS: This was an investigator-blinded randomized study in which 30 patients were randomized 1:1:1 into the following groups: Group 1 patients pretreated for 6-7 days with 5-FU, ALA applied with incubation of 2 hours, ALA removed with wet gauze, illuminated treated areas with 10 J/cm(2) with Blu-U device; Group 2 patients treated with 5-FU BID for 6-7 days and no ALA/PDT; Group 3 patients received no pretreatment, ALA applied with incubation of 2 hours, ALA removed with wet gauze, illuminated treated areas with 10 J.cm2 with Blu-U device. Patients were seen at screening/baseline, treatment for ALA/PDT, 24 hours post treatment, 1 week post treatment and 3 months post treatment. All subjects were then given a re-challenge course of 5-FU for 6 days and reassessed. RESULTS: AK counts in all groups were dramatically decreased and similar at 1 and 3 months post treatment. The re-challenge brought a significant difference with many subclinical lesions in the area of activity in the ALA and 5-FU alone groups. CONCLUSIONS: All three arms appeared equal in treating visible AKs. These data strongly suggests a synergistic role of 5-FU with ALA/PDT over ALA/PDT or 5-FU alone in treating the subclinical lesions demonstrated on a 5-FU re-challenge. Treatment of these subclinical lesions should result in a longer remission. The data also suggests that a 5-FU re-challenge could be a clinical tool to judge the efficacy of treatment for AK if these subclinical lesions are proven to be an AK precursor.

Impact of female acne on patterns of health care resource utilization.

BACKGROUND: Limited data are available on acne treatment patterns in females through their adult years. OBJECTIVE: The purpose of this analysis was to evaluate health care resource utilization (HRU) and treatment patterns in cohorts with and without the use of acne medication and predictors of use. METHODS: A cross-sectional, web-based survey was administered to US females (25-45 years) with facial acne (≥ 25 visible lesions). Data collected included: sociodemographics and self-reported clinical characteristics, acne treatments, and health care professional (HCP) visits. Subject characteristics associated with medication use were examined by logistic regression. RESULTS: Approximately half of the total sample (N=208, mean age: 35 ± 6) ever visited an HCP for acne and reported more over-the counter (OTC) medication use (51.0%) than prescription (Rx) medication use (15.4%). Subjects did not use medications daily, averaging from 12-18 days over the previous 4 weeks. Logistic regression showed that race and prior HCP visits for acne were significant predictors of medication use (P<.05). CONCLUSIONS: Adult females generally self-treated their acne using primarily OTC medications; however, poor compliance was observed for Rx and OTC. Race and prior HCP visits for acne were significant predictors of current medication use.

Optimizing the use of topical brimonidine in rosacea management: panel recommendations.

Rosacea is a chronic inflammatory disease with a complex pathophysiology that manifests with central facial redness with or without papulopustular lesions. Often, patients with rosacea present with a constellation of signs and symptoms; for best results, the treatment plan should take into account all symptoms manifesting in the individual patient. The first available pharmacologic treatment to address the redness associated with rosacea is topical brimonidine. In the United States, brimonidine topical gel 0.33% is indicated for persistent facial erythema of rosacea; approval was based on clinically significant efficacy and good safety data from large-scale clinical trials. Use of brimonidine in routine clinical practice has yielded new insights that elaborate on the findings from clinical trials. For example, real-world use has shown that a percentage of patients (in our experience, approximately 10 to 20%) treated with brimonidine experience a worsening of erythema that has been called "rebound." Our routine use of this agent for >1 year has yielded strategies to set patient expectations, optimize treatment initiation, and minimize potential problems; this article details those strategies. Because we believe that the term "rebound" has been used to describe several physiologically distinct events, we have also proposed more specific terminology for such events.