Recent Advances in Mild and Moisturizing Cleansers

Mild and moisturizing cleanser technologies, and the science underpinning them, have progressed significantly over the past decade. This includes introduction of amino-acid based milder surfactants into the cleansing arena, a deeper understanding of the roles of stratum corneum lipids and proteins in their interaction with cleanser surfactants, the role of pH in skin cleansing, and the development of improved methodologies for predicting skin irritation and drying potential of cleansers. In this paper, the recent advances in these areas as well as newer technologies are reviewed, and the future directions are outlined. J Drugs Dermatol. 2019;18(1 Suppl):s80-88

Practical management of acne for clinicians: An international consensus from the Global Alliance to Improve Outcomes in Acne.

Scientific advances are continually improving the knowledge of acne and contributing to the refinement of treatment options; it is important for clinicians to regularly update their practice patterns to reflect current standards. The Global Alliance to Improve Outcomes in Acne is an international group of dermatologists with an interest in acne research and education that has been meeting regularly since 2001. As a group, we have continuously evaluated the literature on acne. This supplement focuses on providing relevant clinical guidance to health care practitioners managing patients with acne, with an emphasis on areas where the evidence base may be sparse or need interpretation for daily practice.

Efficacy and Safety of Sarecycline, a Novel, Once-Daily, Narrow Spectrum Antibiotic for the Treatment of Moderate to Severe Facial Acne Vulgaris: Results of a Phase 2, Dose-Ranging Study.

BACKGROUND: There is a need for new oral antibiotics for acne with improved safety profiles and targeted antibacterial spectra. Sarecycline is a novel, tetracycline-class antibiotic specifically designed for acne, offering a narrow spectrum of activity compared with currently available tetracyclines, including less activity against enteric Gram-negative bacteria. This phase 2 study evaluated the efficacy and safety of three doses of sarecycline for moderate to severe facial acne vulgaris. METHODS: In this multicenter, double-blind, placebo-controlled study, patients aged 12 to 45 years were randomized to once-daily sarecycline 0.75 mg/kg, 1.5 mg/kg, 3.0 mg/kg, or placebo. Efficacy analyses included change from baseline in inflammatory and noninflammatory lesion counts at week 12, with between-group comparisons using analysis of covariance. Safety assessments included adverse events (AEs), clinical laboratories, vital signs, electrocardiograms, and physical examinations. RESULTS: Overall, 285 randomized patients received at least one dose of study drug. At week 12, sarecycline 1.5 mg/kg and 3.0 mg/kg groups demonstrated significantly reduced inflammatory lesions from baseline (52.7% and 51.8%, respectively) versus placebo (38.3%; P=0.02 and P=0.03, respectively). Sarecycline was safe and well tolerated, with similar gastrointestinal AE rates in sarecycline and placebo groups. Vertigo and photosensitivity AEs occurred in less than 1% of patients when pooling sarecycline groups; no vulvovaginal candidiasis AEs occurred. Discontinuation rates due to AEs were low. No serious AEs occurred. CONCLUSION: Once-daily sarecycline 1.5 mg/kg significantly reduced inflammatory lesions versus placebo and was safe and well tolerated with low rates of AEs, including gastrointestinal AEs. Sarecycline 3.0 mg/kg did not result in additional efficacy versus 1.5 mg/kg. Sarecycline may represent a novel, once-daily treatment for patients with moderate to severe acne. It offers a narrow antibacterial spectrum relative to other tetracycline options, which may lead to less selective pressure on enteric Gram-negative bacteria, resulting in less disruption of commensal organisms and less potential for antibiotic resistance.

J Drugs Dermatol. 2018;17(3):333-338.

Evidence-based recommendations for the management of acne fulminans and its variants.

BACKGROUND: Acne fulminans (AF) is a severe variant of inflammatory acne. It typically manifests as an explosive worsening and ulceration of skin lesions, and can be associated with systemic symptoms. However, there is a paucity of evidence-based information and no clear guidelines concerning the classification and treatment of AF. OBJECTIVE: To better define the spectrum of AF and its variants, devise optimal therapeutic approaches, and identify areas of future research. METHODS: A panel of physicians with expertise in severe acne vulgaris was convened after a comprehensive literature review of severe acne variants. Priority topics were reviewed and presented by each panelist at a 5-hour conference. Following review of the audiotape and scribed notes from the conference, surveys were utilized to address points of controversy and to clarify consensus recommendations. RESULTS: Appropriate clinical case presentations and consensus survey questions were utilized to create final recommendations based on both the literature and the expert consensus. LIMITATIONS: Limited evidenced-based data and prospective studies in the literature concerning the treatment of AF is available. CONCLUSION: These guidelines better characterize AF and provide health care practitioners approaches to the classification, treatment, and prevention of AF and its variants.

Guidelines of care for the management of acne vulgaris.

Acne is one of the most common disorders treated by dermatologists and other health care providers. While it most often affects adolescents, it is not uncommon in adults and can also be seen in children. This evidence-based guideline addresses important clinical questions that arise in its management. Issues from grading of acne to the topical and systemic management of the disease are reviewed. Suggestions on use are provided based on available evidence.

Daily Use of a Facial Broad Spectrum Sunscreen Over One-Year Significantly Improves Clinical Evaluation of Photoaging.

BACKGROUND: Sunscreens are known to protect from sun damage; however, their effects on the reversal of photodamage have been minimally investigated. OBJECTIVE: The aim of the prospective study was to evaluate the efficacy of a facial sun protection factor (SPF) 30 formulation for the improvement of photodamage during a 1-year use. METHODS: Thirty-two subjects applied a broad spectrum photostable sunscreen (SPF 30) for 52 weeks to the entire face. Assessments were conducted through dermatologist evaluations and subjects' self-assessment at baseline and then at Weeks 12, 24, 36, and 52. RESULTS: Clinical evaluations showed that all photoaging parameters improved significantly from baseline as early as Week 12 and the amelioration continued until Week 52. Skin texture, clarity, and mottled and discrete pigmentation were the most improved parameters by the end of the study (40% to 52% improvement from baseline), with 100% of subjects showing improvement in skin clarity and texture. CONCLUSION: The daily use of a facial broad-spectrum photostable sunscreen may visibly reverse the signs of existing photodamage, in addition to preventing additional sun damage.

One-year topical stabilized retinol treatment improves photodamaged skin in a double-blind, vehicle-controlled trial.

BACKGROUND: Retinol, a precursor of retinoic acid, has great potentials as a topical anti-aging molecule; however, only a handful of clinical investigations have been published to date. OBJECTIVE: This study aimed to assess the efficacy and safety of 0.1% stabilized retinol on photodamaged skin during a one-year treatment. METHODS: The investigation included two 52-week, double-blind, vehicle-controlled studies. In the main study, 62 subjects applied either a stabilized retinol formulation or its vehicle to the full face. A second exploratory study evaluated histological/histochemical markers in 12 subjects after 52 weeks of either retinol or vehicle use on contralateral dorsal forearms. RESULTS: The retinol group showed significant photodamage improvement over vehicle at all timepoints during the study. After 52 weeks, retinol had improved crow's feet fine lines by 44%, and mottled pigmentation by 84%, with over 50% of subjects showing +2 grades of improvement in many parameters. Additionally, at week 52, histochemical data confirmed the clinical results, showing increased expression of type I procollagen, hyaluronan, and Ki67 as compared to vehicle. CONCLUSION: This study confirms that a stabilized retinol (0.1%) formulation can significantly improve the signs of photoaging, and improvements in photodamage continue with prolonged use.

Understanding and Reducing the Risk for Acne Scarring.

Scarring is a lifelong, physically disfiguring and often emotionally debilitating sequela resulting from acne vulgaris. Nearly 80% of patients have some scarring and 50% have clinically relevant scarring. Although the extent, duration, and intensity of inflammation are important risk factors, scarring also can develop in patients with relatively mild inflammation. Assessment of scarring should be part of the evaluation in all patients with acne and should be a consideration in determining treatment. Semin Cutan Med Surg 34(supp5):S89-S91 © 2015 published by Frontline Medical Communications.

Reliability of Clinician Erythema Assessment grading scale.

BACKGROUND: Facial erythema is a clinical hallmark of rosacea and often causes social and psychological distress. Although facial erythema assessments are a common endpoint in rosacea clinical trials, their reliability has not been evaluated. OBJECTIVE: The objective of this study was to evaluate the inter- and intrarater reliability of the Clinician's Erythema Assessment (CEA), a 5-point grading scale of facial erythema severity. METHODS: Twelve board-certified dermatologists, previously trained on use of the scale, rated erythema of 28 rosacea subjects twice on the same day. Interrater and intrarater agreement was assessed with the intraclass correlation and κ statistic. RESULTS: The CEA had high interrater reliability and good intrarater reliability with an overall intraclass correlation coefficient (ICC) for session 1 and session 2 of 0.601 and 0.576, respectively; the overall weighted κ statistic for session 1 and session 2 was 0.692. LIMITATIONS: Raters were experienced dermatologists and there may be a risk of recall bias. CONCLUSION: When used by trained raters, CEA is a reliable scale for measuring the facial erythema of rosacea.

Randomized, phase 2, dose-ranging study in the treatment of rosacea with encapsulated benzoyl peroxide gel.

OBJECTIVE: Compare the safety and efficacy of 1% and 5% silica encapsulated benzoyl peroxide (E-BPO) in patients with papulopustular rosacea. DESIGN: Multi-centered randomized, double blind, vehicle controlled parallel group, 12 week treatment in 92 patients with papulopustular rosacea. Primary endpoints were dichotomized IGA with success defined as clear/near clear and reduction in inflammatory lesions. PATIENTS: 92 patients: 74% graded as moderate IGA, 14% severe and 12% mild. The mean inflammatory lesion count was 24. INTERVENTION: Once daily treatment for 12 weeks with vehicle, 1% or 5% E-BPO. RESULTS: 1% and 5% E-BPO were superior to vehicle in reducing papulopustular lesions P =0.01 and P =0.02. 5% E-BPO was superior to vehicle for IGA P =0.0013.

Results of a Phase III, double-blind, randomized, parallel-group, non-inferiority study evaluating the safety and efficacy of isotretinoin-Lidose in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin-Lidose, the first new formulation of isotretinoin in 30 years, differs from previously approved isotretinoin formulations in that it is less dependent on the presence of fat in the gut for absorption. OBJECTIVE: Evaluate the safety profiles of isotretinoin-Lidose and food-dependent generic isotretinoin in the largest clinical study with isotretinoin-925 randomized patients from 49 study sites. Determine if the efficacy of this new formulation is noninferior to an existing isotretinoin. METHODS: Multicenter, double-blind, randomized, parallel-group, noninferiority trial. Study medication was taken with meals twice daily for 20 weeks. Patients were followed for 4 weeks after the last dose. Safety evaluations included recordings of adverse events, assessments for depression, anxiety, emergent psychotic symptoms, and suicidal ideation/behavior, as well as DEXA and X-ray evaluations and changes in bone age. Two co-primary efficacy outcomes were measured to assess noninferiority: a) change in total nodular facial and truncal lesion count at from baseline to week 20 and b) percentage of patients who experienced at least 90% reduction in nodular facial and truncal lesion count from baseline to week 20. LIMITATIONS: Although isotretinoin-Lidose can be taken without meals, it was given with food because the absorption of both formulations in the study had to be similar to detect noninferiority. RESULTS: The safety profile of the 2 formulations was comparable. Criteria for noninferiority for both co-primary efficacy outcomes were met based on predetermined margins. CONCLUSION: Safety and efficacy of isotretinoin-Lidose is similar and noninferior to food-dependent generic isotretinoin, respectively.

Comparative pharmacokinetic profiles of a novel isotretinoin formulation (isotretinoin-Lidose) and the innovator isotretinoin formulation: a randomized, 4-treatment, crossover study.

BACKGROUND: A high-fat meal is needed for optimal absorption of isotretinoin. A new formulation of isotretinoin, which enhances absorption of isotretinoin in the absence of dietary fat, has recently been approved by the Food and Drug Administration (FDA). OBJECTIVE: We sought to compare the pharmacokinetic profiles of a new formulation of isotretinoin (isotretinoin-Lidose) with the innovator isotretinoin formulation. METHODS: This study was an open-label, single-dose, randomized, 4-treatment, crossover comparative trial between a new and innovator formulation of isotretinoin in the fasting and fed states. RESULTS: Both formulations were bioequivalent under fed conditions. As expected in a fasting state, absorption of both formulations was reduced. A considerable difference between the 2 drugs occurred under fasted conditions-there was a marked improvement in overall bioavailability of the isotretinoin-Lidose formulation. Mean plasma levels of the isotretinoin-Lidose formulation during fasting reached 66.8% of that observed with a fatty meal, and those of the isotretinoin formulation only reached 39.6% of that observed with a fatty meal. LIMITATIONS: Only the FDA-stipulated standard high-fat, high-calorie meal of 50-g fat was studied in the fed state. CONCLUSION: Isotretinoin-Lidose formulation is bioequivalent to the innovator formulation under fed conditions with regard to its pharmacokinetic profile but delivers twice as much isotretinoin and 4-oxo-isotretinoin when administered after an overnight fast.

New insights into rosacea pathophysiology: a review of recent findings.

Rosacea is a common, chronic inflammatory skin disease of poorly understood origin. Based on its clinical features (flushing, chronic inflammation, fibrosis) and trigger factors, a complex pathobiology involving different regulatory systems can be anticipated. Although a wealth of research has shed new light over recent years on its pathophysiology, the precise interplay of the various dysregulated systems (immune, vascular, nervous) is still poorly understood. Most authors agree on 4 major clinical subtypes of rosacea: erythematotelangiectatic rosacea, papulopustular rosacea, phymatous rosacea, and ocular rosacea. Still, it needs to be elucidated whether these subtypes develop in a consecutive serial fashion or if any subtypes may occur individually as part of a syndrome. Because rosacea often affects multiple family members, a genetic component is also suspected, but the genetic basis of rosacea remains unclear. During disease manifestation and early stage, the innate immune system and neurovascular dysregulation seem to be driving forces in rosacea pathophysiology. Dissection of major players for disease progression and in advanced stages is severely hampered by the complex activation of the innate and adaptive immune systems, enhanced neuroimmune communication, profound blood vessel and possibly lymphatic vessel changes, and activation of almost every resident cell in the skin. This review discusses some of the recent findings and aims to build unifying hypotheses for a modern understanding of rosacea pathophysiology.

A randomized, phase 2, dose-ranging study in the treatment of moderate to severe inflammatory facial acne vulgaris with doxycycline calcium.

BACKGROUND: Doxycycline calcium (WC2055) is a drug substance with a possible role in the treatment of acne. The objective of this study was to evaluate the safety and efficacy of three doses of doxycycline calcium tablets compared with placebo in the treatment of moderate to severe inflammatory facial acne vulgaris. METHODS: This was a randomized, double-blind, phase 2 dose-ranging study in subjects with moderate to severe inflammatory acne aged 12 years to 45 years. Subjects were randomized to receive doxycycline calcium tablets 0.6, 1.2, or 2.4 mg/kg/day or placebo, and instructed to take their tablets once daily for 12 weeks, in the evening at least 1 hour before or 2 hours after mealtime. The primary efficacy variables were the dichotomized Investigator's Global Assessment score (success or failure) at week 12 (success defined as ≥ 2 score decrease from baseline) and the absolute change from baseline to week 12 in inflammatory lesion count. RESULTS: A dose-response effect was seen with doxycycline calcium formulation in subjects with moderate to severe inflammatory acne. The highest dose-group (corresponding to approximately 2.4 mg/kg/day) showed a statistically significant difference from placebo. The dose-response effect was confirmed by logistic regression analysis for both treatment success and incidence of gastrointestinal adverse events. A limitation of this study is that safety and efficacy were only studied on moderate to severe inflammatory acne. Also, the study was not prospectively powered to show efficacy differences. CONCLUSION: Doxycycline calcium shows a dose-response effect in reducing inflammatory lesions in subjects with moderate to severe inflammatory acne.

In vivo antibacterial effects of tretinoin-clindamycin and clindamycin alone on Propionibacterium acnes with varying clindamycin minimum inhibitory.

OBJECTIVE: To quantify the antimicrobial effect of clindamycin phosphate 1.2% and tretinoin 0.025% gel and 1% clindamycin phosphate gel in patients with Propionibacterium acnes of varying sensitivity to clindamycin. DESIGN: Study 1 was an initial range-finding study that was neither blinded nor randomized. Study 2 was an open-label, randomized, splitface, single-center study. Both studies were conducted in Pennsylvania. PATIENTS: Study 1 (n=20) and study 2 (n=22) involved healthy patients aged 18 years or older with initial P acnes levels #104/cm2 and minimum inhibitory concentrations (MICs) #8 µg/mL for clindamycin. INTERVENTIONS: Study 1, clindamycin gel applied twice daily for 6 weeks. Study 2; once-daily application with the combination gel to one cheek and clindamycin gel to the other side for 6 weeks. MAIN OUTCOME MEASURE: The comparative effectiveness of each product vs P acnes of varying sensitivity to clindamycin at 3 and 6 weeks posttreatment. RESULTS: For study 1, at 3 and 6 weeks, clindamycin-treated patients with MICs of %256 µg/mL showed greater reductions than those with MICs #512 µg/mL (P=.0001). Study 2 showed a significant reduction in P acnes for both products, with no differences found. Clindamycin alone was more effective in vivo in patients with MIC levels of %256 µg/mL than patients with higher MIC levels. The combination product produced a greater reduction than clindamycin alone after 6 weeks in patients with high MICs #512 µg/mL (P=.0047). CONCLUSION: These studies suggest that 1% clindamycin alone produces a varying in vivo antimicrobial effect, with a breakpoint at %256 µg/mL. Use of clindamycin phosphate 1.2% and tretinoin 0.025% gel resulted in a significantly greater in vivo antimicrobial effect than clindamycin alone in patients carrying P acnes with MICs of #512 µg/mL (P=.0047).

The effect of benzoyl peroxide 9.8% emollient foam on reduction of Propionibacterium acnes on the back using a short contact therapy approach.

Benzoyl peroxide (BP) exerts its therapeutic effect for acne vulgaris through reduction of Propionibacterium acnes. A 1.0 to 2.0 log reduction in P acnes has been demonstrated primarily on the face with use of "leave-on" BP formulations, but also with some BP cleansers. In addition to use for facial acne vulgaris, cleanser formulations of BP are commonly used for truncal acne vulgaris due to ease of use on a large body-surface area and to avoid bleaching of fabric. To date, evaluation of P acnes reduction on the trunk has not been well studied with BP formulations, especially with the use of recognized and standardized methods to accurately determine P acnes colony counts. A previous study demonstrated that a BP 8% cleanser did not reduce counts of P acnes on the back when subjects were instructed to apply the cleanser in the shower, allow it to dry for 20 seconds on the skin, and then rinse off the cleanser. Evaluation of specified time intervals between application on the back and rinsing with BP formulations would help to better define the necessary skin contact time associated with high reductions of P acnes (>90%), recognizing also the potential roles of BP concentration and vehicle. This 2 week study using quantitative bacteriologic cultures evaluates the effectiveness of BP 9.8% emollient foam in reducing P acnes levels on the back with 2 minutes of skin contact time and compares results with a BP 5.3% "leave-on" emollient foam formulation. Short contact therapy utilizing a 2 minute skin contact time with BP 9.8% emollient foam used once daily over a 2 week duration was highly effective in reducing the quantity of P acnes organisms on the back and provided comparable colony count reduction to "leave on" therapy using BP 5.3% emollient foam.

Effects of topical retinoid therapy on acne lesions: a psychometric assessment.

Topical retinoids are believed to increase inflammatory lesions within the first few weeks of treatment. We evaluated data from several clinical trials for evidence of a signal for retinoid aggravation of inflammatory lesions using a psychometric method and the proportion of participants who demonstrated varying degrees of increased lesion counts. We first determined the validity of a psychometric method based on Stevens' power law called the visual logarithmic scale (VLS) used to evaluate the perceived changes in inflammatory lesions. There was concurrence between the VLS model and the dermatologists' visual assessment of a flare in 80.0% (32/40) of participants (P=.0258). A subsequent analysis was performed using data from clinical trials to assess the occurrence of flares using the VLS model or percentage-based definitions (5%, 10%, or 20% increase) following the first week of treatment with various adapalene gel formulations. In this analysis, no evidence of worsening or a flare was seen by either the VLS model or percentage-based definitions. The VLS model is valid for assessing the changes in acne severity. Topical retinoid treatment was not associated with a flare as measured by either the VLS model or the proportion of participants who showed an increase in inflammatory lesions.

Efficacy of a novel rosacea treatment system: an investigator-blind, randomized, parallel-group study.

INTRODUCTION: A rosacea treatment system (cleanser, metronidazole 0.75% gel, hydrating complexion corrector, and sunscreen SPF30) has been developed to treat rosacea. METHODS: Thirty women with mild or moderate erythema of rosacea on their facial cheeks were randomly assigned to use one of the following for 28 days: the rosacea treatment system (RTS); RTS minus metronidazole (RTS-M); or metronidazole 0.75% gel plus standard skin care (standard cleanser and standard moisturizer/sunscreen) (M+SSC). RESULTS: At day 28, global improvement was evident in 90 percent of patients using RTS, 60 percent using RTS-M, and 67 percent using M+SSC. Erythema was significantly lower with RTS from day 14 onward, and unchanged with M+SSC. The proportion of patients reporting their skin was easily irritated at least sometimes was 40 percent with RTS, 70 percent with RTS-M, and 89 percent with M+SSC. CONCLUSION: The rosacea treatment system may offer superior efficacy and tolerability to metronidazole plus the standard skin care used in this study.

Efficacy of benzoyl peroxide (5.3%) emollient foam and benzoyl peroxide (8%) wash in reducing Propionibacterium acnes on the back.

BACKGROUND: Topical treatment of acne vulgaris on the back is challenging largely due to the extensive broad surface with difficult to reach areas. A "leave-on" foam is suited for application to the trunk due to ease of application and spreadability. Prior to this trial, no data on Propionibacterium acnes (P. acnes) reduction on the back has existed for any benzoyl peroxide (BP) formulations or other acne treatments. OBJECTIVES: To evaluate the effectiveness of BP (5.3%) emollient foam and BP (8%) wash in reducing P. acnes levels on the back. METHODS: Five-week open-label single-center study of 20 healthy subjects (> 18 years old), colonized with P. acnes on their backs (> 10,000 colonies per cm2). Subjects were treated once daily with BP (5.3%) foam for two weeks; no treatment in week 3, and BP (8%) wash once daily for two further weeks. Quantitative bacteriologic cultures obtained at baseline and weeks 1, 2, 3, 5 and 6. RESULTS: Nineteen evaluable patients. Total P. acnes counts were reduced by 1.9 log (one week) and 2.1 log (two weeks) with BP (5.3%) emollient foam. BP (8%) wash did not reduce P. acnes counts after two weeks. DISCUSSION: BP (5.3%) emollient foam was superior to BP (8%) wash in reducing P. acnes on the back. The lack of effect of BP (8%) wash is surprising in view of the demonstrated results on the face and warrants further study.