A Practical Algorithm for Integrating Skincare to Improve Patient Outcomes and Satisfaction With Energy-Based Dermatologic Procedures.

BACKGROUND: Medical aesthetic procedures for facial antiaging with laser and energy-based devices (EBDs) are rapidly increasing, but standards integrating skincare before, during, and after these treatments are lacking. The algorithm for integrated skin care for facial antiaging treatment with EBDs aims to stimulate healing, reduce downtime, and improve comfort and treatment outcomes. METHODS: A panel of 8 global physicians employed a modified Delphi method and reached a consensus on the algorithm integrating skincare based on the best available evidence, the panel's clinical experience, and opinions. RESULTS: The algorithm has a pretreatment (starts 2 - 4 weeks before the procedure) and treatment (day of treatment) section, followed by care after the procedure (0 - 7 days) and follow-up care (1 - 4 weeks after the procedure or ongoing). Applying a broad-spectrum sunscreen with an SPF 50 or higher, combined with protective measures such as wearing a wide-brimmed hat and sunglasses, is recommended to protect the face from sun exposure. Dyschromia is a significant concern for those with skin of color (SOC). Clinicians may recommend skincare using a gentle cleanser and moisturizer containing vitamins C and E, retinoid, or other ingredients such as niacinamide, kojic acid, licorice root extract, azelaic acid, and tranexamic acid, depending on the patient's facial skin condition. CONCLUSION: Medical aesthetic procedures for facial antiaging with EBDs integrating skincare or topical treatments may improve outcomes and patient satisfaction. Topical antioxidants and free radical quenchers can combat photodamage and may offer a safe alternative to topical hydroquinone.  J Drugs Dermatol. 2024;23(5):353-359.     doi:10.36849/JDD.8092.

The Real-World Effectiveness and Tolerability of a Soothing Cream Containing the Postbiotic Aquaphilus dolomiae Extract-G2 for Skin Healing.

INTRODUCTION: In vitro and pre-marketing clinical data have shown the healing properties of a postbiotic extract from Aquaphilus dolomiae (ADE-G2). The effectiveness and tolerability of an ADE-G2-based cream were therefore evaluated for the management of minor skin impairment and wound healing in a large population of subjects in routine clinical practice. METHODS: A real-world, international, pre-post comparative study was conducted in infants, children, and adults with various types of superficial skin impairment who used the study product daily for around 3 weeks according to their dermatologist's advice. Immediate and follow-up changes in dermatologic signs and symptoms were assessed through clinical scoring. User satisfaction, overall product effectiveness, and tolerability were also evaluated. Analyses were performed in the whole study population and in subject subgroups according to skin impairment type and age. RESULTS: Overall, 1317 subjects (83.1% adults, 72.0% female) were included. Dermatologists reported effectiveness and "good" or "very good" tolerability of the cream in 93.8% (1221/1302) and 98.5% (1278/1297) of subjects, respectively. Immediate symptom relief after the first application was reported by 88.3% (849/962) of subjects. After several weeks of regular use (16.7 ± 11.6 days), dermatologic signs and symptoms significantly improved in the whole study population and in the subgroups, with mean decreases in severity scores ranging from -34.5% to -92.5% (p < 0.0001). The smallest improvements were found in subjects with oncologic treatment-related skin impairment. At study end, most users (> 95%) were "very satisfied" or "satisfied" with the cream and found that skin healing was rapid and of good quality. CONCLUSION: The ADE-G2-based cream proved to be effective and well tolerated in real-life conditions for the management of minor skin impairment in a large and varied cohort of subjects. This product, used as a standalone or adjunctive regimen, can help accelerate the healing of various types of superficial skin impairment.

Evaluation of a retinol containing topical treatment to improve signs of neck aging.

BACKGROUND: The neck region is an area that can be indicative of signs of skin aging. A novel topical product that combines multiple active ingredients including retinol, tripeptide and glaucine was formulated to specifically target neck aging correction and complement post-procedure as part of an integrated skincare regimen. OBJECTIVES: To evaluate the efficacy of a topical neck treatment through clinical subject evaluation, in addition to ultrasound and biopsy assessment. METHODS: Evaluation for the efficacy of this novel topical product on improving the aging signs of neck skin was performed in multiple clinical trials. The first trial focused on clinical efficacy and included clinical assessment, subject questionnaires, ultrasound imaging and digital photographs. The second trial focused on biomarker analysis through skin biopsy. RESULTS: Data from the clinical trials showed that aging signs on the neck were significantly improved after 12 or 16 weeks of product usage. Changes were readily observed by clinical evaluators and participants. They were documented with digital photos, ultrasound images, and biomarker expression in the skin which clearly display the improvements. CONCLUSIONS: This novel topical product is effective in treating the aging signs on the neck skin and has been shown to provide statistically significant improvement on a myriad of neck aging attributes including fine lines/wrinkles, crepiness, laxity, and texture.

Supplement Article: Skin Barrier Deficiency in Rosacea: An Algorithm Integrating OTC Skincare Products Into Treatment Regimens.

INTRODUCTION: Rosacea is a chronic condition involving inflammation leading to a diminished skin barrier function in sebaceous gland-rich facial skin. The current algorithm represents part II of a series investigating similar topics associated with preventing, treating, and maintaining rosacea, including ceramides-containing skincare. METHODS: The consensus process consisted of a modified Delphi technique. A previously published review by the US Cutaneous Rosacea Outcomes (USCRO) group on skin barrier deficiency in rosacea and the integration of over-the-counter (OTC) products and skincare recommended for rosacea treatment and maintenance informed the development of the current algorithm. The selected information from the literature searches, coupled with the USCRO group's opinion and experience, was used to develop, discuss, and reach a consensus on an evidence-based clinical treatment and maintenance algorithm focusing on rosacea phenotypes. RESULTS: The algorithm includes foundational measures to be taken by all patients with rosacea and rosacea-prone skin. These measures include education, behavioral modifications, avoidance of triggers and skin irritants, preventative skincare, and sun avoidance and sunscreen use. The algorithm further describes how assessment of skin condition and grading of cutaneous rosacea should take place during treatment and maintenance while the preventative measures continue. CONCLUSIONS: Prescription medications combined with gentle cleansers, moisturizers, and sunscreen support a successful rosacea therapy. J Drugs Dermatol. 2022;21:9(Suppl 1):s3-10.

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial.

Importance: Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT). Objectives: To determine the efficacy and safety of topical synthetic hypericin ointment, 0.25%, activated with visible light as a nonmutagenic PDT in early-stage MF/CTCL. Design, Settings, and Participants: This was a multicenter, placebo-controlled, double-blinded, phase 3 randomized clinical trial (FLASH study) conducted from December 2015 to November 2020 at 39 academic and community-based US medical centers. Participants were adults (≥18 years) with early-stage (IA-IIA) MF/CTCL. Interventions: In cycle 1, patients were randomized 2:1 to receive hypericin or placebo to 3 index lesions twice weekly for 6 weeks. In cycle 2, all patients received the active drug for 6 weeks to index lesions. In cycle 3 (optional), both index and additional lesions received active drug for 6 weeks. Main Outcomes and Measures: The primary end point was index lesion response rate (ILRR), defined as 50% or greater improvement in modified Composite Assessment of Index Lesion Severity (mCAILS) score from baseline after 6 weeks of therapy for cycle 1. For cycles 2 and 3, open label response rates were secondary end points. Adverse events (AEs) were assessed at each treatment visit, after each cycle, and then monthly for 6 months. Data analyses were performed on December 21, 2020. Results: The study population comprised 169 patients (mean [SD] age, 58.4 [16.0] years; 96 [57.8%] men; 120 [72.3%] White individuals) with early-stage MF/CTCL. After 6 weeks of treatment, hypericin PDT was more effective than placebo (cycle 1 ILRR, 16% vs 4%; P = .04). The ILRR increased to 40% in patients who received 2 cycles of hypericin PDT (P < .001 vs cycle 1 hypericin) and to 49% after 3 cycles (P < .001 vs cycle 1 hypericin). Significant clinical responses were observed in both patch and plaque type lesions and were similar regardless of age, sex, race, stage IA vs IB, time since diagnosis, and number of prior therapies. The most common treatment-related AEs were mild local skin (13.5%-17.3% across cycles 1-3 vs 10.5% for placebo in cycle 1) and application-site reactions (3.2%-6.9% across cycles 1-3 vs 4% for placebo in cycle 1). No drug-related serious AEs occurred. Conclusion and Relevance: The findings of this randomized clinical trial indicate that synthetic hypericin PDT is effective in early-stage patch and plaque MF/CTCL and has a favorable safety profile. Trial Registration: ClinicalTrials.gov Identifier: NCT02448381.

Safety, Pharmacodynamic Response, and Treatment Satisfaction With OnabotulinumtoxinA 40 U, 60 U, and 80 U in Subjects With Moderate to Severe Dynamic Glabellar Lines.

BACKGROUND: OnabotulinumtoxinA 20 U reduces glabellar line (GL) severity at maximum frown for approximately 3 to 4 months. Small studies have suggested that >20-U doses may increase the efficacy and duration of response for GLs. OBJECTIVES: The aim of this study was to evaluate safety, pharmacodynamic response, and treatment satisfaction with onabotulinumtoxinA doses ≥20 U for GLs. METHODS: This 48-week, double-blind study compared 40, 60, and 80 U onabotulinumtoxinA vs 20 U and placebo in women with moderate or severe dynamic GLs on the Allergan Facial Wrinkle Scale. The following parameters were evaluated: the percentage of subjects with investigator-assessed ≥1-grade Facial Wrinkle Scale improvement from baseline at maximum frown (responders) at Week 24; the estimated median duration of response; the proportion of mostly/very satisfied responders on the Facial Line Satisfaction Questionnaire follow-up Items 1 to 5; and treatment-emergent adverse events. RESULTS: The modified intent-to-treat population (N = 226) had a mean age of 48.0 years, with similar baseline GL severity between treatment groups. Week 24 responder rates were 0% for placebo and 16.0%, 32.0%, 30.6%, and 38.5% for onabotulinumtoxinA 20, 40, 60, and 80 U, with significant (P < 0.05) differences for 40 and 80 U vs 20 U. Median duration of response was longer with all higher doses vs 20 U (≥24.0 vs 19.7 weeks; P < 0.05 vs 20 U at Week 24). Facial Line Satisfaction Questionnaire results indicated high subject satisfaction. The incidence and severity of treatment-emergent adverse events did not exhibit a dose-response effect. CONCLUSIONS: GL treatment with onabotulinumtoxinA doses >20 U demonstrated longer duration of response and higher patient-reported satisfaction vs the on-label 20-U dose with no apparent impact on safety variables.

Long-Term Skin Clearance With Brodalumab in Patients With Psoriasis and Inadequate Response to Prior Biologics.

BACKGROUND: Despite the emergence of multiple biologic drug options for psoriasis, unmet treatment needs remain. Biologic therapies can vary in their effectiveness and adverse events, and many patients experience a loss of treatment effect over time. After lack of response, treatment may be switched to a biologic with a different mechanism of action. Brodalumab, a human interleukin-17 (IL-17) receptor A antagonist, is approved for the treatment of adult patients with moderate-to-severe psoriasis with inadequate response or loss of response to prior systemic therapies. Because brodalumab targets the IL-17 receptor instead of the ligand itself, it not only targets a broader set of IL-17 isoforms but also may be effective in patients who received prior IL-17 inhibitors or failed to respond to anti–IL-17 treatment. This is supported by long-term evidence from clinical trials and real-world studies of patients receiving brodalumab who were previously treated with IL-17 inhibitors. Additionally, brodalumab produces reliable treatment effects after use of biologics with other mechanisms of action, such as tumor necrosis factor α and IL-12/IL-23 inhibitors, as well as after the use of multiple biologic therapies. For patients with psoriasis with inadequate response to one or more biologic therapies, brodalumab is an option that has the ability to lead to long-term skin clearance. J Drugs Dermatol. 2022;21(3):364-370. doi:10.36849/JDD.6743.

SUPPLEMENT ARTICLE: Scientific and Clinical Insights into the Facial Application of Mineralizing Volcanic Water.

BACKGROUND: The term "exposome" describes the totality of exposures an individual is subjected to from conception to death. Both internal and external exposome factors affect skin health. External exposures that contribute to facial skin aging include solar radiation, air pollution, tobacco smoke, and unbalanced nutrition. The review explores scientific and clinical insights into the exposome impact on facial skin aging and topical mineralizing volcanic water use potential benefits. METHODS: An expert panel of seven dermatologists and two clinical researchers specializing in aesthetic and dermatological indications reviewed and discussed the literature on the exposome and mineralizing volcanic water's role in relation to the exposome. Two virtual advisory boards were conducted between February and May 2021. Following the meetings, an additional systematic literature review explored publications relevant to the exposome, topical essential minerals, and skin health. The results of the two advisory boards, coupled with expert opinion and the outcome of the updated systematic literature review, informed the statements on which the advisors reached a consensus. CONCLUSIONS: A combination of in vivo, in vitro, and clinical data on topical mineralizing volcanic water application indicates that the serum supports the skin's antioxidant defenses and reduces skin inflammation. Additionally, the serum may have benefits as an adjunct for facial dermatoses and post-procedural skincare. J Drugs Dermatol. 2022;21:4(Suppl 1):s3-10.

Safety and Efficacy of Nano-Pulse Stimulation Treatment of Non-Genital, Cutaneous Warts (Verrucae).

BACKGROUND AND OBJECTIVES: This study describes the effects of nano-pulse stimulation (NPS) technology on the common verruca with the objectives of demonstrating efficacy and safety. NPS technology applies nanosecond pulses of non-thermal electrical energy to induce highly localized regulated cell death in the cellular structures of the targeted zone with negligible effects on surrounding non-cellular structures. Previous clinical studies applying NPS to common, benign skin lesions have demonstrated safety and efficacy in clearing seborrheic keratoses and sebaceous hyperplasia. STUDY DESIGN/MATERIALS AND METHODS: Sixty-two subjects were enrolled at a total of five sites. One hundred and ninety-five study verrucae up to 10 mm wide were treated with NPS delivered by a console-based handheld applicator (CellFX® System; Pulse Biosciences) and follow-ups occurred every 30 days with the option to retreat at 30, 60, and 90 days. There were 62 untreated controls and 46% of the treated verrucae were recalcitrant. RESULTS: Overall, 75.3% (70/93) of the common verrucae, 72.7% (8/11) of the flat verrucae, and 43.8% (14/32) of the plantar verrucae treated with NPS were completely clear by 60 days following the last treatment and did not recur within the 120-day observation period. The majority (54%) of verrucae cleared with a single NPS procedure. The most common treatment site reactions were erythema (50.5%) and eschar formation (23.4%) on Day 30 and on Day 120 mild erythema was present in 14% of the cases and hyperpigmentation in 18.5%. No serious adverse events were reported. A particle counter was used during 11 NPS procedures on verrucae and no significant plume generation was detected during these procedures. CONCLUSIONS: NPS is a safe and effective procedure for removing non-genital, cutaneous verrucae. Lasers Surg. Med. © 2021 The Authors. Lasers in Surgery and Medicine published by Wiley Periodicals LLC.

Evidence of Barrier Deficiency in Rosacea and the Importance of Integrating OTC Skincare Products into Treatment Regimens.

BACKGROUND: Rosacea, an inflammatory skin disease that leads to an impaired skin barrier function commonly involves the face. Symptoms of rosacea can be bothersome and include pain, stinging, burning, itching, and facial flushing. This review explored skin barrier impairment in rosacea and reduced symptomatology when using over the counter (OTC) skincare products. METHODS: Nine dermatologists (the panel) completed a survey on OTC products they recommend for rosacea. The survey results were summarized, presented, and discussed during the online meeting, together with the results of a literature review. The outcome of these discussions, coupled with the panel's expert opinion and experience, is shown in the current review. RESULTS: Addressing barrier dysfunction by use of moisturizer and cleanser formulations that restore skin hydration, normalize skin pH, restore the microbiome, and skin lipids can assist in improving rosacea signs and symptoms. The panel's consensus was that in addition to the use of prescription medications, skincare recommendations are a crucial part of successful rosacea therapy. In addition to occlusives and humectants, barrier restoring ingredients such as ceramides, hyaluronic acid, and niacinamide were considered beneficial. Equally important was the absence of potentially irritating substances. CONCLUSIONS: The use of OTC products can improve rosacea symptomatology and signs. As adjuncts, these products are recommended before and during prescription therapy and as part of a maintenance regimen. J Drugs Dermatol. 20(4):384-392. doi:10.36849/JDD.5861 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL fTEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.

Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials.

BACKGROUND: Baricitinib, a selective Janus kinase 1/Janus kinase 2 inhibitor, is indicated in the European Union and Japan for the treatment of moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. OBJECTIVE: The objective of this study was to evaluate the safety of baricitinib 2 mg in the AD clinical program. METHODS: Six double-blind, randomized, placebo-controlled studies, and two long-term extension studies were summarized in two datasets. Placebo comparison was based on six 16-week studies with baricitinib 2 mg. All-bari-2-mg-AD included patients who received baricitinib 2 mg at any time during the eight studies. RESULTS: In total, 1598 patients received once-daily baricitinib 2 mg for 1434.2 patient-years of exposure (median 330 days/maximum 2.4 years). Treatment-emergent adverse events were higher for baricitinib 2 mg (57.9%) vs placebo (51.6%). Serious adverse events, serious infections, and opportunistic infections were low in frequency and similar between baricitinib 2 mg and placebo. There were no malignancies, gastrointestinal perforations, or major adverse cardiovascular events with baricitinib 2 mg in the placebo-controlled period. Herpes simplex (cluster) was higher for baricitinib 2 mg (3.8%) vs placebo (2.8%); rates decreased with extended 2 mg exposure. In All-bari-2-mg-AD, there were five malignancies other than non-melanoma skin cancer, two major adverse cardiovascular events, one peripheral venous thrombosis, one arterial thrombosis, and no pulmonary embolisms, deep vein thromboses, or deaths. CONCLUSIONS: This integrated analysis in patients with moderate-to-severe AD confirms the established safety profile of baricitinib 2 mg. Longer exposure to treatment is required to evaluate risks of malignancies and major adverse cardiovascular events. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT02576938 (first posted 15 October, 2015); NCT03334396 (7 November, 2017); NCT03334422 (7 November, 2017); NCT03428100 (9 February, 2018); NCT03435081 (15 February, 2018); NCT03733301 (7 November, 2018); NCT03334435 (7 November, 2017); NCT03559270 (18 June, 2018).

Baricitinib is a medication that helps an overactive immune system adjust itself, leading to improvements in the inflammatory condition atopic dermatitis. Baricitinib is approved for patients with moderate-to-severe atopic dermatitis in 40 countries. Because it works with the immune system, it is important to understand the safety of baricitinib. Safety information was collected from eight studies and analyzed in two datasets. The first dataset compared the safety of baricitinib 2 mg with placebo in six 16-week studies in which neither patient nor physician knew whether they were taking baricitinib or placebo. The second dataset included an additional two extension studies and examined the safety of baricitinib in all patients receiving at least one dose of baricitinib 2 mg. Patients took baricitinib 2 mg for a maximum of 2.4 years, with a median time of 330 days. In the first dataset, adverse events were higher for baricitinib 2 mg (57.9%) than placebo (51.6%). Serious adverse events, serious infections, and opportunistic infections were low in number and similar for patients taking baricitinib 2 mg or placebo. Herpes simplex infections were more frequent in patients taking baricitinib 2 mg (3.8%) than in those taking placebo (2.8%), but rates in those taking baricitinib 2 mg decreased with a longer treatment duration. There were no occurrences of cancer, gastrointestinal perforations, or major adverse cardiovascular events. In the second dataset, there were five reports of cancer other than non-melanoma skin cancer, two major adverse cardiovascular events, one peripheral venous thrombosis, one arterial thrombosis, and no pulmonary embolisms, deep vein thromboses, or deaths. Longer treatment with baricitinib is required to better understand the risks of developing cancer or major adverse cardiovascular events. This analysis of safety in patients with moderate-to-severe atopic dermatitis is consistent with the safety reported previously for baricitinib 2 mg. Extended Safety Analysis of Baricitinib 2 mg in Adult Patients with Atopic Dermatitis: An Integrated Analysis from Eight Randomized Clinical Trials (MP4 87244 kb).

Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis.

BACKGROUND: The tubulin polymerization and Src kinase signaling inhibitor tirbanibulin is being investigated as a topical treatment for actinic keratosis, a precursor of squamous-cell carcinoma. METHODS: In two identically designed double-blind trials, we randomly assigned, in a 1:1 ratio, adults with actinic keratoses on the face or scalp to receive either topical tirbanibulin or vehicle (placebo) ointment. The ointment was applied by the patients to a 25-cm2 contiguous area containing four to eight lesions once daily for 5 consecutive days. The primary outcome was the percentage of patients with a complete (100%) reduction in the number of lesions in the application area at day 57. The secondary outcome was the percentage of patients with a partial (≥75%) reduction in the number of lesions within the application area at day 57. The incidence of recurrence was evaluated at 1 year. Local reactions were scored with the use of 4-point scale (ranging from 0 [absent] to 3 [severe]). RESULTS: A total of 702 patients were enrolled in the two trials (351 patients per trial). Complete clearance in trial 1 occurred in 44% of the patients (77 of 175) in the tirbanibulin group and in 5% of those (8 of 176) in the vehicle group (difference, 40 percentage points; 95% confidence interval [CI], 32 to 47; P<0.001); in trial 2, the percentages were 54% (97 of 178 patients) and 13% (22 of 173), respectively (difference, 42 percentage points; 95% CI, 33 to 51; P<0.001). The percentages of patients with partial clearance were significantly higher in the tirbanibulin groups than in the vehicle groups. At 1 year, the estimated percentage of patients with recurrent lesions was 47% among patients who had had a complete response to tirbanibulin. The most common local reactions to tirbanibulin were erythema in 91% of the patients and flaking or scaling in 82%. Adverse events with tirbanibulin were application-site pain in 10% of the patients and pruritus in 9%, all of which resolved. CONCLUSIONS: In two identically designed trials, tirbanibulin 1% ointment applied once daily for 5 days was superior to vehicle for the treatment of actinic keratosis at 2 months but was associated with transient local reactions and recurrence of lesions at 1 year. Trials comparing tirbanibulin with conventional treatments and that have longer follow-up are needed to determine the effects of tirbanibulin therapy on actinic keratosis. (Funded by Athenex; ClinicalTrials.gov numbers, NCT03285477 and NCT03285490.).

Topical Oxymetazoline Cream 1.0% for Persistent Facial Erythema Associated With Rosacea: Pooled Analysis of the Two Phase 3, 29-Day, Randomized, Controlled REVEAL Trials

Background: Rosacea is a chronic dermatologic condition with limited treatment options. Methods: Data were pooled from two identically designed phase 3 trials. Patients with moderate to severe persistent erythema of rosacea were randomized to receive oxymetazoline cream 1.0% or vehicle once daily for 29 days and were followed for 28 days posttreatment. The primary efficacy outcome was the proportion of patients with ≥2-grade improvement from baseline on both Clinician Erythema Assessment (CEA) and Subject Self-Assessment (SSA) at 3, 6, 9, and 12 hours postdose, day 29. Results: The pooled population included 885 patients (78.8% female); 85.8% and 91.2% had moderate erythema based on CEA and SSA, respectively. The primary outcome was achieved by significantly more patients in the oxymetazoline than vehicle group (P<0.001). Individual CEA and SSA scores and reduction in facial erythema (digital image analysis) favored oxymetazoline over vehicle (P<0.001). The incidence of treatment-emergent adverse events was low (oxymetazoline, 16.4%; vehicle, 11.8%). No clinically relevant erythema worsening (based on CEA and SSA) was observed during the 28-day posttreatment follow-up period (oxymetazoline, 1.7%; vehicle, 0.6%). Conclusion: Oxymetazoline effectively reduced moderate to severe persistent facial erythema of rosacea and was well tolerated. J Drugs Dermatol. 2018;17(11):1201-1208.

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.

Pharmacokinetics and Safety of Ingenol Disoxate Gel Administered Under Maximum-Use Conditions to Patients With Actinic Keratosis.

BACKGROUND AND OBJECTIVES: Ingenol disoxate (LEO 43204) is a field therapy in development for the treatment of actinic keratosis (AK) on areas between 25 and 250 cm2. We evaluated the systemic exposure and safety of ingenol disoxate under maximum-use conditions. METHODS: This was a phase I, open-label, non-randomized, multicenter trial. Patients ≥ 18 years of age with ≥ 15 clinically typical, visible, discrete AK lesions in a treatment area on the full face or approximately 250 cm2 on the arm or scalp were treated once-daily for 3 consecutive days with ingenol disoxate 0.018, 0.1, or 0.037% gel, respectively. RESULTS: The trial included 58 patients. Median age (range) of patients was 68 years (42-89) [face, N = 18], 66 years (43-88) [arm, N = 21], and 67 years (37-83) [scalp, N = 19]. The highest quantifiable ingenol disoxate level was observed in the arm group (0.33 nM, area under the concentration-time curve from time zero to the last data point [AUCtlast] 3.12 nM·h). Mean composite local skin response scores peaked at Day 4 and declined towards baseline by Day 15 in all treatment groups. Most adverse events (AEs) were of mild or moderate intensity; the most common treatment-related AEs were application-site pain (face, 88.9%; arm, 57.1%; scalp, 100.0%) and application-site pruritus (face, 50.0%; arm, 52.4%; scalp, 42.1%). CONCLUSION: Very low systemic exposure to ingenol disoxate was observed when applied to the face, arm, or scalp in patients with AK under maximum-use conditions. No new safety signals were identified. TRIAL REGISTRATION: NCT02424305.

Treatment of Rosacea With Concomitant Use of Topical Ivermectin 1% Cream and Brimonidine 0.33% Gel: A Randomized, Vehicle-controlled Study.

BACKGROUND: There is currently a lack of data on the simultaneous treatment of different features of rosacea. Individually, ivermectin 1% (IVM) cream and brimonidine 0.33% (BR) gel have demonstrated efficacy on inflammatory lesions and persistent erythema, respectively. OBJECTIVE: To evaluate the efficacy, safety, patient satisfaction, and optimal timing of administration of IVM associated with BR (IVM+BR) versus their vehicles in rosacea (investigator global assessment [IGA] ≥3). METHODS: Multicenter, randomized, double-blind study including subjects with rosacea characterized by moderate to severe persistent erythema and inflammatory lesions. The active treatment group included the IVM+BR/12 weeks subgroup (once-daily BR and once-daily IVM for 12 weeks), and the IVM+BR/8 weeks subgroup (once-daily BR vehicle for 4 weeks followed by once-daily BR for the remaining 8 weeks and once-daily IVM for 12 weeks). The vehicle group received once-daily BR vehicle and once-daily IVM vehicle for 12 weeks. RESULTS: The association showed superior efficacy (IGA success [clear/almost clear]) for erythema and inflammatory lesions in the total active group (combined active subgroups) compared to vehicle (55.8% vs. 36.8%, P=0.007) at week 12. The success rate increased from 32.7% to 61.2% at hour 0 and hour 3, respectively, in the IVM+BR/12 weeks subgroup, and from 28.3% to 50% in the IVM+BR/8 weeks subgroup. Reductions in erythema and inflammatory lesion counts confirmed the additive effect of BR to IVM treatment. Subjects reported greater improvement in the active subgroups than in the vehicle group, and similar rates for facial appearance satisfaction after the first 4 weeks of treatment in both active subgroups. All groups showed similar tolerability profiles. CONCLUSION: Concomitant administration of IVM cream with BR gel demonstrated good efficacy and safety, endorsing the comprehensive approach to this complex disease. Early introduction of BR, along with a complete daily skin care regimen may accelerate treatment success without impairing tolerability.

J Drugs Dermatol. 2017;16(9):909-916.

Eosinophilic cellulitislike reaction to subcutaneous etanercept injection.

BACKGROUND: Injection site reactions are well recognized in patients treated with etanercept. Previous reports describe histologic findings of a cell-mediated T(H)1 reaction, with CD8+ T cells composing the majority of the dermal infiltrate. OBSERVATIONS: A pruritic, erythematous, edematous patch occurred on the right thigh of a 57-year-old white woman treated for rheumatoid arthritis within 12 to 24 hours after her second dose of subcutaneous etanercept. The patient had a similar reaction to adalimumab injection 2 weeks prior to presentation. While benzyl alcohol is present in the etanercept preparation, and mannitol in both drugs, dermal injection revealed no reaction to these additives. Biopsy specimens from the etanercept injection site demonstrated papillary dermal edema accompanied by a brisk polymorphous infiltrate with a predominance of eosinophils and scattered flame figures. CONCLUSIONS: Histologic features of eosinophilic cellulitis as a response to etanercept have not been reported to date. Although most injection site reactions contain T cells and represent a T(H)1 immune response, the findings we report suggest a T(H)2-mediated phenomenon.

Agminated Spitz nevi: report of a child with a unique dermatomal distribution.

Spitz nevi most commonly present as solitary lesions. Multiple agminated Spitz nevi are a rare presentation, with 38 reported cases in the English language literature. We report a 2-year-old girl who presented with multiple Spitz nevi in a unique, dermatome-like distribution and review the English-language literature on agminated Spitz nevi.

Early and explosive development of nodular basal cell carcinoma and multiple keratoacanthomas in psoriasis patients treated with cyclosporine.

The use of cyclosporine to treat psoriasis has been widely adopted since 1997, when the microemulsion form (Neoral) became available. While the causal relationship between cyclosporine and the development of malignant neoplasms has been well described in the transplant literature, it is difficult to apply this relationship to cyclosporine-treated psoriasis, since lower dosages are used (3-5 mg/kg/d vs. 7-15mg/kg/d) for a shorter duration. Current literature suggests that cancer risk is not increased when cyclosporine is used in dermatologic doses for less than 2 years in healthy patients who are not on other immunosuppressants. We report two patients with explosive basal cell carcinoma and keratoacanthoma development, respectively, within 3 months of initiation of cyclosporine. Neither patient had a history of skin cancer, had received PUVA therapy, or was on additional immunosuppressive therapy. To our knowledge, there have been no previous reports of the development of similar lesions in cyclosporine-treated psoriatic patients within such a short timeframe. The results of these patients may herald the need for increased awareness by dermatologists for explosively-growing neoplasms in the setting of cyclosporine-treated psoriasis.