Roflumilast foam 0.3% for adolescent and adult patients with seborrheic dermatitis: A randomized, double-blinded, vehicle-controlled, phase 3 trial.

BACKGROUND: The topical phosphodiesterase 4 inhibitor roflumilast has been studied in several dermatologic conditions. OBJECTIVE: Roflumilast foam 0.3% is being investigated as a topical treatment for seborrheic dermatitis (SD). METHODS: In this phase 3, double-blinded trial, patients with SD were randomly assigned (2:1 ratio) to once-daily roflumilast foam 0.3% or vehicle foam for 8 weeks. The primary efficacy outcome was Investigator Global Assessment (IGA) Success at week 8, defined as IGA of 0 (Clear) or 1 (Almost Clear) plus ≥2-point improvement from baseline. Safety was also assessed. RESULTS: 79.5% of roflumilast-treated and 58.0% of vehicle-treated patients met the primary endpoint (P < .001); statistically significant differences in IGA Success also favored roflumilast at week 2 (roflumilast: 43.0%; vehicle: 25.7%; P < .001) and week 4 (roflumilast: 73.1%; vehicle: 47.1%; P < .001). Roflumilast was well-tolerated with a low rate of treatment-emergent adverse events. LIMITATIONS: Study limitations include the 8-week treatment period for this chronic condition. CONCLUSIONS: Once-daily roflumilast foam was superior to vehicle in leading to IGA of Clear or Almost Clear plus ≥2-point improvement from baseline at 8 weeks in patients with SD. Longer trials are needed to determine durability and safety of roflumilast foam in SD.

Application Characteristics and Patient Preference of Triple-Combination vs Layered Topicals for Acne: Split-Face Study.

BACKGROUND: Although triple-combination therapies for acne are generally more efficacious than dual-combinations or topical monotherapy, this benefit may be offset by reduced adherence to a complicated treatment regimen. Clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB; Cabtreo®, Ortho Dermatologics) gel is the first triple-combination topical approved for the treatment of acne. By delivering multiple active ingredients as a fixed-dose combination, CAB gel may improve ease of use, which can benefit both treatment adherence and efficacy. The objective of this study was to compare the application characteristics of CAB gel with the layered application of its 3 individual active ingredients. METHODS: In this split-face study, adults with acne-prone skin (N=25), self-applied CAB gel (0.3 cc) to 1 side of the face and layered benzoyl peroxide cream, adapalene gel, and clindamycin gel (0.1 cc each) on the opposite side. CAB and clindamycin gels were compounded with pyranine, which fluoresces under blue light. Photos taken under blue light were used to assess the uniformity of product application, and participants rated the evenness, speed, and ease of the 2 application regimens, as well as overall preference. RESULTS: Investigator-assessed evenness of application favored CAB gel over layered application in 100% of participants. All participants rated the application of CAB gel as more uniform, easier, and faster. Most (96%) preferred CAB gel for use at home. CONCLUSION: Fixed-dose CAB gel was applied more evenly than separate application of its 3 active ingredients. By addressing 3 of the main acne pathogenic pathways in a single, easy-to-apply formulation, CAB gel may improve the efficacy of and adherence to acne treatment. J Drugs Dermatol. 2024;23(10):857-861. doi:10.36849/JDD.8430.

A Silymarin Antioxidant Serum Improves Facial Acne Alone and as Part of a Treatment Regimen.

BACKGROUND: Silymarin is an antioxidant that can protect against free radicals that cause premature signs of aging and oil oxidation that may contribute to breakouts. AIMS: The objective of these studies was to evaluate a silymarin antioxidant serum alone and in combination with a prescription acne treatment regimen in improving facial appearance in blemish-prone skin.  Methods: Two international studies were conducted. A 12-week study in Brazil enrolled 56 subjects to examine the effect of silymarin antioxidant serum on facial acne. Clinical grading on acne lesions, skin tone, clarity, and postinflammatory hyperpigmentation (PIH) were conducted. In addition, consumer self-assessment, analysis for markers of lipid peroxidation, and sebumeter analysis were completed. Another Unites States (US)/German study enrolled 40 subjects who were on topical prescription acne medications to which silymarin antioxidant serum was added. Acne lesion counts, tolerability, and facial appearance assessments were conducted in this study. RESULTS: The Brazilian study demonstrated a 45% reduction in inflammatory lesions and a 43% reduction in noninflammatory lesions after 12 weeks of silymarin antioxidant serum use. In addition, sebumeter testing showed a 16% reduction in oiliness at week 1. The US/German study showed the benefits of the serum in persons already on prescription acne therapy by reducing facial erythema by 60%, dryness by 49%, and scaling by 67%. CONCLUSION: Silymarin is shown in clinical testing to have significant benefits in reducing lipid peroxidation, oiliness, and PIH, and in improving key markers of skin aging. Additionally, the serum can be used alone or as an adjunctive treatment in acne therapy to further benefit aging, acne-prone skin. J Drugs Dermatol. 2024;23(4):     doi:10.36849/JDD.8120.

Clindamycin Phosphate 1.2%/Adapalene 0.15%/Benzoyl Peroxide 3.1% Gel in Participants With Moderate-to-Severe Acne: The Patient Journey.

INTRODUCTION: Topical clindamycin phosphate 1.2%/adapalene 0.15%/benzoyl peroxide 3.1% (CAB) gel is the only fixed-dose, triple-combination formulation approved for acne treatment. In 3 clinical studies of participants with moderate-to-severe acne, CAB demonstrated superior efficacy to vehicle and component dyads, with good safety and tolerability. Detailed efficacy/safety data from individual clinical study participants are presented. METHODS: In two phase 3 (NCT04214652, NCT04214639) randomized, double-blind, 12-week studies, participants aged at least 9 years with moderate-to-severe acne were randomized to once-daily CAB or vehicle gel. Descriptive data - including lesion count changes, treatment success (at least 2-grade reduction from baseline in Evaluator's Global Severity Score and clear/almost clear skin), compliance, treatment-emergent adverse events (AEs), and cutaneous safety/tolerance assessments - were summarized from 6 CAB-treated cases. RESULTS: By week 12, all cases achieved >70% lesion reductions, 4/6 achieved treatment success, and 1/6 achieved a 2-grade reduction in severity. All cases were compliant with CAB treatment. No cases reported serious AEs. Transient increases occurred on cutaneous safety and tolerability assessments, with scores generally decreasing back to/below baseline levels by week 12. CONCLUSIONS: In two phase 3 clinical trials, fixed-dose, triple-combination CAB demonstrated good efficacy/safety. All 6 CAB-treated cases achieved substantial (>70%) lesion reductions, with 5/6 achieving treatment success or 2-grade reduction in severity by week 12. Transient cutaneous safety/tolerability severity increases generally resolved to baseline values by week 12. These clinical study cases reinforce the importance of patient education regarding adherence, expectations, and AEs. J Drugs Dermatol. 2024;23(11):1017-1024. doi:10.36849/JDD.8639.

International Consensus on Anti-Aging Dermocosmetics and Skin Care for Clinical Practice Using the RAND/UCLA Appropriateness Method.

BACKGROUND: The objective was to provide international recommendations on anti-aging dermocosmetics for clinical practice starting with essential ingredients for protection and repair before working up to advanced products for specific concerns.  Methods: Seven international experts reviewed 8 hypothetical case scenarios covering different ages, skin issues (eg, sensitivity, acne, melasma), and exposure to exposome factors for both sexes and all Fitzpatrick skin types (FST). The RAND/UCLA appropriateness method was used to obtain consensus. Seventeen key ingredients were rated on a scale from 1 (totally inappropriate) to 9 (totally appropriate). Statistical analysis, 2 meetings, and email discussions refined the recommendations. RESULTS: High-factor broad-spectrum sunscreen (ie, protects against ultraviolet [UV] A and B rays), niacinamide, and other topical antioxidants were recommended for all scenarios. Further discussions were required for other ingredients. Tinted sunscreen/iron oxide were recommended for all FST, although compliance may be sub-optimal for darker skin phototypes (IV-VI), if not cosmetically acceptable. Combining a facial foundation with broad-spectrum sunscreen was recommended for darker phototypes to obtain visible light protection closely matching diverse color tones. Retinols were not recommended as a first-line treatment for sensitive skin, especially FST V and VI, due to the risk of irritation. After ablative laser treatment, alpha hydroxy acids should be avoided or used with caution in FST IV to VI due to the risk of post-inflammatory hyperpigmentation. CONCLUSION: We describe a simple, practical tool for use in daily dermatology consultations for providing recommendations on anti-aging dermocosmetics to cover diverse and inclusive populations of patients, addressing all skin types and international needs.  J Drugs Dermatol. 2024;23(1):1337-1343.     doi:10.36849/JDD.7798.

Trial of Roflumilast Cream for Chronic Plaque Psoriasis.

BACKGROUND: Systemic oral phosphodiesterase type 4 (PDE-4) inhibitors have been effective in the treatment of psoriasis. Roflumilast cream contains a PDE-4 inhibitor that is being investigated for the topical treatment of psoriasis. METHODS: In this phase 2b, double-blind trial, we randomly assigned adults with plaque psoriasis in a 1:1:1 ratio to use roflumilast 0.3% cream, roflumilast 0.15% cream, or vehicle (placebo) cream once daily for 12 weeks. The primary efficacy outcome was the investigator's global assessment (IGA) of a status of clear or almost clear at week 6 (assessed on a 5-point scale of plaque thickening, scaling, and erythema; a score of 0 indicates clear, 1 almost clear, and 4 severe). Secondary outcomes included an IGA score indicating clear or almost clear plus a 2-grade improvement in the IGA score for the intertriginous area and the change in the Psoriasis Area and Severity Index (PASI) score (range, 0 to 72, with higher scores indicating worse disease). Safety was also assessed. RESULTS: Among 331 patients who underwent randomization, 109 were assigned to roflumilast 0.3% cream, 113 to roflumilast 0.15% cream, and 109 to vehicle cream. An IGA score indicating clear or almost clear at week 6 was observed in 28% of the patients in the roflumilast 0.3% group, in 23% in the roflumilast 0.15% group, and in 8% in the vehicle group (P<0.001 and P = 0.004 vs. vehicle for roflumilast 0.3% and 0.15%, respectively). Among the approximately 15% of patients overall who had baseline intertriginous psoriasis of at least mild severity, an IGA score at week 6 indicating clear or almost clear plus a 2-grade improvement in the intertriginous-area IGA score occurred in 73% of the patients in the roflumilast 0.3% group, 44% of those in the roflumilast 0.15% group, and 29% of those in the vehicle group. The mean baseline PASI scores were 7.7 in the roflumilast 0.3% group, 8.0 in the roflumilast 0.15% group, and 7.6 in the vehicle group; the mean change from baseline at week 6 was -50.0%, -49.0%, and -17.8%, respectively. Application-site reactions occurred with similar frequency in the roflumilast groups and the vehicle group. CONCLUSIONS: Roflumilast cream administered once daily to affected areas of psoriasis was superior to vehicle cream in leading to a state of clear or almost clear at 6 weeks. Longer and larger trials are needed to determine the durability and safety of roflumilast in psoriasis. (Funded by Arcutis Biotherapeutics; ARQ-151 201 ClinicalTrials.gov number, NCT03638258.).

Once-daily roflumilast foam 0.3% for scalp and body psoriasis: a randomized, double-blind, vehicle-controlled phase IIb study.

BACKGROUND: Scalp psoriasis affects most patients with psoriasis, but it can be difficult to treat. OBJECTIVES: To evaluate the efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. METHODS: In a phase IIb randomized controlled trial, adults and adolescents aged ≥ 12 years with scalp and body psoriasis were randomized (2 : 1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp Investigator Global Assessment (S-IGA) success (score of 'clear' or 'almost clear' plus ≥ 2-grade improvement from baseline) at week 8. Safety and tolerability were also evaluated. RESULTS: Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved S-IGA success at week 8 (P < 0.001); differences favoured roflumilast as early as the first postbaseline visit at week 2 (P < 0.001). Significant improvements were also seen for secondary endpoints, including body IGA success, Scalp Itch Numeric Rating Scale and the Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs), with few discontinuations due to an AE. Few patients with skin of colour (11%) and few adolescents (0.7%) were included. CONCLUSIONS: The results support the further development of roflumilast foam for treating scalp and body psoriasis.

DMT310, a novel once-weekly topical treatment for patients with moderate-to-severe acne vulgaris: Results of a phase 2b randomized, double-blind, placebo-controlled trial.

BACKGROUND: Poor patient adherence with antiacne medications is a common clinical challenge. DMT310, a natural, topical product with a once-weekly application schedule, may alleviate this obstacle. OBJECTIVE: Evaluate the safety, tolerability, and efficacy of DMT310 in treating moderate-to-severe acne. METHODS: This 12-week, randomized, double-blind, placebo-controlled, multicenter clinical trial enrolled participants 12 years and older with moderate-to-severe acne. RESULTS: The intent-to-treat population included a total of 181 participants (DMT310, N = 91; placebo, N = 90). Participants who received DMT310 vs participants treated with placebo demonstrated a statistically significant greater reduction in the number of inflammatory and noninflammatory lesions at all time points: inflammatory lesion counts at week 12 (-15.64 vs -10.84, P < .001); noninflammatory lesion counts at week 12 (-18.26 vs -12.41, P < .001). DMT310-treated participants also had higher rates of Investigator's Global Assessment treatment success than participants in the placebo group at all time points: Investigator's Global Assessment at week 12 (44.40% vs 17.78%; P < .001). No serious treatment related adverse events occurred. CONCLUSIONS: DMT310 once-weekly topical treatment significantly reduced both inflammatory and noninflammatory lesions and yielded a greater proportion of Investigator's Global Assessment treatment success at all time points in participants with moderate-to-severe acne.

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.

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.

Photoprotection for all: Current gaps and opportunities.

The effects of solar radiation on human skin differ based on the skin phototype, presence or absence of photodermatoses, biologic capacity to repair DNA damage, wavelength, intensity of sun exposure, geographic latitude, and other factors, underscoring the need for a more tailored approach to photoprotection. To date, the focus of photoprotection guidelines has been to prevent sunburn and DNA damage induced by UV radiation, both UVB and UVA; however, several recent studies have shown that visible light also generates reactive oxygen and nitrogen species that can contribute to skin damage and pigmentation on the skin, particularly in people with skin of color. Therefore, individuals with dark skin, while naturally better protected against UVB radiation by virtue of the high eumelanin content in melanocytes, may need additional protection from visible light-induced skin damage. The current options for photoprotection products need to expand, and potential strategies against visible light include the addition of iron oxide, titanium dioxide, and biologically relevant antioxidants to sunscreen formulations as well as supplementation with orally active antioxidants.

Photoprotection for skin of all color: Consensus and clinical guidance from an expert panel.

The negative effects of sun exposure have become better accepted among health care professionals and the lay public over recent decades. Most attention has been focused on the effects of UV light, particularly UVB wavelengths (290-320 nm). Accordingly, products to protect skin from sunlight-associated harm (sunscreens) have been developed to minimize UVB exposure. The effects of longer wavelengths, including UVA (320-400 nm) and visible light (VL, 400-700 nm), are increasingly appreciated. VL accounts for approximately half of the solar radiation that reaches the earth's surface and understanding of its effects on the skin is improving. Studies have shown that VL can induce hyperpigmentation in individuals with dark skin types (Fitzpatrick skin types IV-VI). In addition, VL can contribute to the exacerbation of pigmentary disorders, including melasma. Because these findings are relatively new, there are gaps in understanding the needs for photoprotection and guidance for clinicians. A panel of dermatologists and photobiologists was convened to develop consensus recommendations and clinical guidance about sunscreen use relevant to the current understanding of risks associated with sun exposure using a modified Delphi method.

Effect of Roflumilast Cream vs Vehicle Cream on Chronic Plaque Psoriasis: The DERMIS-1 and DERMIS-2 Randomized Clinical Trials.

Importance: Once-daily roflumilast cream, 0.3%, a potent phosphodiesterase 4 inhibitor, demonstrated efficacy and was well tolerated in a phase 2b trial of patients with psoriasis. Objective: To evaluate the efficacy of roflumilast cream, 0.3%, applied once daily for 8 weeks in 2 trials of patients with plaque psoriasis. Design, Setting, and Participants: Two phase 3, randomized, double-blind, controlled, multicenter trials (DERMIS-1 [trial 1; n = 439] and DERMIS-2 [trial 2; n = 442]) were conducted at 40 centers (trial 1) and 39 centers (trial 2) in the US and Canada between December 9, 2019, and November 16, 2020, and between December 9, 2019, and November 23, 2020, respectively. Patients aged 2 years or older with plaque psoriasis involving 2% to 20% of body surface area were enrolled. The dates of final follow-up were November 20, 2020, and November 23, 2020, for trial 1 and trial 2, respectively. Interventions: Patients were randomized 2:1 to receive roflumilast cream, 0.3% (trial 1: n = 286; trial 2: n = 290), or vehicle cream (trial 1: n = 153; trial 2: n = 152) once daily for 8 weeks. Main Outcomes and Measures: The primary efficacy end point was Investigator Global Assessment (IGA) success (clear or almost clear status plus ≥2-grade improvement from baseline [score range, 0-4]) at week 8, analyzed using a Cochran-Mantel-Haenszel test stratified by site, baseline IGA score, and intertriginous involvement. There were 9 secondary outcomes, including intertriginous IGA success, 75% reduction in Psoriasis Area and Severity Index (PASI) score, and Worst Itch Numeric Rating Scale score of 4 or higher at baseline achieving 4-point reduction (WI-NRS success) at week 8 (scale: 0 [no itch] to 10 [worst imaginable itch]; minimum clinically important difference, 4 points). Results: Among 881 participants (mean age, 47.5 years; 320 [36.3%] female), mean IGA scores in trial 1 were 2.9 [SD, 0.52] for roflumilast and 2.9 [SD, 0.45] for vehicle and in trial 2 were 2.9 [SD, 0.48] for roflumilast and 2.9 [SD, 0.47]) for vehicle. Statistically significantly greater percentages of roflumilast-treated patients than vehicle-treated patients had IGA success at week 8 (trial 1: 42.4% vs 6.1%; difference, 39.6% [95% CI, 32.3%-46.9%]; trial 2: 37.5% vs 6.9%; difference, 28.9% [95% CI, 20.8%-36.9%]; P < .001 for both). Of 9 secondary end points, statistically significant differences favoring roflumilast vs vehicle were observed for 8 in trial 1 and 9 in trial 2, including intertriginous IGA success (71.2% vs 13.8%; difference, 66.5% [95% CI, 47.1%-85.8%] and 68.1% vs 18.5%; difference, 51.6% [95% CI, 29.3%-73.8%]; P < .001 for both), 75% reduction in PASI score (41.6% vs 7.6%; difference, 36.1% [95% CI, 28.5%-43.8%] and 39.0% vs 5.3%; difference, 32.4% [95% CI, 24.9%-39.8%]; P < .001 for both), WI-NRS success (67.5% vs 26.8%; difference, 42.6% [95% CI, 31.3%-53.8%] and 69.4% vs 35.6%; difference, 30.2% [95% CI, 18.2%-42.2%]; P < .001 for both). The incidence of treatment-emergent adverse events was 25.2% with roflumilast vs 23.5% with vehicle in trial 1 and 25.9% with roflumilast vs 18.4% with vehicle in trial 2. The incidence of serious adverse events was 0.7% with roflumilast vs 0.7% with vehicle in trial 1 and 0% with roflumilast vs 0.7% with vehicle in trial 2. Conclusions and Relevance: Among patients with chronic plaque psoriasis, treatment with roflumilast cream, 0.3%, compared with vehicle cream resulted in better clinical status at 8 weeks. Further research is needed to assess efficacy compared with other active treatments and to assess longer-term efficacy and safety. Trial Registration: ClinicalTrials.gov Identifiers: NCT04211363, NCT04211389.

Development of a Tape-Stripping Liquid Chromatography-Mass Spectrometry Method for Evaluating Skin Deposition of Topical Tazarotene.

BACKGROUND: Standard in vitro and ex vivo techniques for evaluating topical drug penetration utilize skin that is physiologically unlike living skin and cannot assess intra-dermal drug deposition. We combined tape stripping with liquid chromatography-heated electrospray ionization-mass spectrometry (LC-ESI-MS) to assess in vivo deposition of tazarotene after application of 0.1% cream and 0.045% lotion formulations. METHODS: Ten healthy adult female participants had ~0.1 g of tazarotene lotion and cream applied to two sites each on opposite forearms. After 3 and 6 hours, 21 tape strips were used to sample progressively deeper skin layers. LC-ESI-MS was used to determine percent recovery of the applied tazarotene dose and the concentration of tazarotene recovered from even-numbered tape strips. RESULTS: At both sampling times, percent recovery was slightly higher with tazarotene 0.045% lotion versus 0.1% cream, though tazarotene concentrations were approximately 2-fold higher for cream than lotion at both superficial and deep skin layers. Absolute differences in tazarotene concentrations between 0.1% cream and 0.045% lotion decreased in progressively deeper skin layers, from 0.8 μg/mL at tape strip 2 to 0.09 μg/mL at tape strip 20 (6 hours post-application). CONCLUSIONS: Tape stripping plus LC-ESI-MS—a consistent, accurate, and non-invasive method for assessing drug delivery into layers of living skin—can be used to assess in vivo deposition of topical formulations. Results from this study, when combined with clinical data, suggest that small tazarotene-deposition differences between lotion and cream in deeper skin layers are not clinically relevant; however, lower-dose 0.045% lotion may minimize tazarotene skin exposure versus 0.1% cream, potentially resulting in a more favorable tolerability profile. J Drugs Dermatol. 2021;20(10):1105-1111. doi:10.36849/JDD.6211.

The Effect of a Ceramide-Containing Product on Stratum Corneum Lipid Levels in Dry Legs.

Roughly equimolar concentrations of ceramides, cholesterol, and free fatty acids arranged in lamellar sheets form the intercellular lipid barrier in the stratum corneum (SC). Intercellular lipid deficiencies, specifically ceramides, and barrier disruption are associated with many dermatologic conditions, including dry skin. This study explored the relationship between the improvement in the signs of dry skin and the amounts of ceramides in the SC by combining clinical observations with a biochemical analysis to quantify the level of SC intercellular lipids. The efficacy of a multilamellar vesicular emulsion (MVE), ceramide-containing moisturizing cream was evaluated in a randomized, investigator-blinded, split-leg study on female subjects with dry, itchy skin. The cream increased skin hydration and demonstrated an immediate and sustained reduction in the visible signs of dry skin and subject perceived sensory discomfort. Additionally, ceramide, cholesterol and free fatty acid levels in the SC significantly increased after 4 weeks of moisturizer application. Thus, the clinical effect of the ceramide-containing moisturizing cream on dry, itchy skin was accompanied by an increase in SC intercellular lipid levels. J Drugs Dermatol. 2020;19(4):372-376. doi:10.36849/JDD.2020.4796.

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.

Combination Superficial Peels With Salicylic Acid and Post-Peel Retinoids.

BACKGROUND: Salicylic acid (SA) and retinoids, tretinoin (all-trans retinoic acid [ATRA]), and retinol (all-trans retinol) are widely used as topical agents for the improvement of photodamage and acne vulgaris. They can be used in daily take-home products or as part of an in-office procedure, combining the benefits of a keratolytic (SA) and a retinoid. OBJECTIVE: The objective of this research was to compare the efficacy for ameliorating photodamage of topical tretinoin (0.25%) and retinol (0.25%) to baseline and with each other when applied after a 30% salicylic acid peel on human facial skin. METHODS: Twenty female subjects received a full face 30% SA peel followed by the overnight application of tretinoin to a 1 randomized half-face and retinol to the opposite side (split-face study). The identical procedure was repeated at week 2. Double-blinded subject and investigator assessments of the results were captured at weeks 2 and 4. RESULTS: By investigator evaluation, both peeling regimens were effective in improving photodamage parameters compared to baseline. (ATRA P-values at week 4 were: P=.00008 texture, P=.00013 roughness, P=.00221 pores, P=.00098 dryness, P=.02770 erythema, and P=.00008 overall appearance. Retinol P-values at week 4 were: P=.00019 texture, P=.00053 roughness, P=.00221 pores, P=.00147 dryness, P=.02770 erythema, and P=.0043 overall appearance.) By subject self-assessment compared with baseline, both tretinoin and retinol were effective in improving overall appearance (ATRA P=.0229 and retinol P=.0190). By investigator evaluation comparing tretinoin with retinol, tretinoin was slightly better than retinol at week 4 in improving texture P=.00506, roughness P=.01171, and overall appearance P=.00506. By subject self-assessment comparing tretinoin with retinol, there was no difference in overall appearance (ATRA P=.2367 and retinol P=.3613). CONCLUSION: Either topical tretinoin (0.25%) or retinol (0.25%) can be used safely and effectively when applied in office immediately after SA peeling to ameliorate signs of photoaging.

Skin cancer and photoprotection in people of color: a review and recommendations for physicians and the public.

Skin cancer is less prevalent in people of color than in the white population. However, when skin cancer occurs in non-whites, it often presents at a more advanced stage, and thus the prognosis is worse compared with white patients. The increased morbidity and mortality associated with skin cancer in patients of color compared with white patients may be because of the lack of awareness, diagnoses at a more advanced stage, and socioeconomic factors such as access to care barriers. Physician promotion of skin cancer prevention strategies for all patients, regardless of ethnic background and socioeconomic status, can lead to timely diagnosis and treatment. Public education campaigns should be expanded to target communities of color to promote self-skin examination and stress importance of photoprotection, avoidance of tanning bed use, and early skin cancer detection and treatment. These measures should result in reduction or earlier detection of cutaneous malignancies in all communities. Furthermore, promotion of photoprotection practices may reduce other adverse effects of ultraviolet exposure including photoaging and ultraviolet-related disorders of pigmentation.