Efficacy and Safety of Microencapsulated Benzoyl Peroxide Cream, 5%, in Rosacea: Results From Two Phase III, Randomized, Vehicle-Controlled Trials.

Objective: A new formulation of benzoyl peroxide (E-BPO cream, 5%) entraps benzoyl peroxide (BPO) in silica microcapsules. This study assesses the efficacy, safety, and tolerability of E-BPO cream, 5%, in rosacea in two Phase III clinical trials. Methods: In two 12-week, randomized, double-blind, vehicle cream-controlled Phase III trials, 733 subjects at least 18 years old with moderate to severe rosacea were randomized (2:1) to once-daily E-BPO cream, 5%, or vehicle. Results: In Study 1, the proportion of subjects achieving IGA clear/almost clear at Week 12 was 43.5 percent for E-BPO cream, 5%, and 16.1 percent for vehicle. In Study 2, the respective values were 50.1 percent and 25.9 percent. In Study 1, the decrease in lesion count from baseline to Week 12 was -17.4 for E-BPO cream, 5%, versus -9.5 for vehicle. In Study 2, the respective values were -20.3 and -13.3 (all P<0.001). The difference was also significant at Week 2. There were no treatment-related serious adverse events; 1.4 percent of subjects (1.8% E-BPO cream, 5%, 0.4% vehicle) discontinued due to adverse events. Assessed local tolerability was found to be similar among subjects in both E-BPO and vehicle.E-BPO was not compared with unencapsulated BPO. Conclusion: E-BPO is an effective and well tolerated treatment for rosacea. Clinicaltrials.gov Identifiers: NCT03564119, NCT03448939.

BPX-01 Minocycline Topical Gel Shows Promise for the Treatment of Moderate-to-severe Inflammatory Acne Vulgaris.

Background and objectives: Acne vulgaris is a highly prevalent and multifactorial skin disorder that can adversely impact health-related quality of life. Factors that contribute to the pathogenesis of acne include pilosebaceous proliferation of proinflammatory Propionibacterium acnes (P. acnes) bacteria, presence of circulating androgens, excess sebum production, abnormal follicular keratinization, and multiple inflammatory cascades. Oral tetracyclines-especially doxycycline and minocycline-are frequently prescribed for the treatment of moderate-to-severe acne, given their anti-inflammatory properties and their effect on P. acnes reduction. Notwithstanding their established efficacy in the management of acne vulgaris, there is a desire to limit systemic exposure to antibiotics given growing concerns regarding bacterial resistance as well as the potential for serious side effects. This report describes outcomes of two randomized, vehicle-controlled trials (Phases IIa and IIb) of BPX-01, a topical minocycline gel, in the treatment of moderate-to-severe acne. Methods: In Study 1 (NCT02709096), at a single center, 33 subjects with highly fluorescing facial skin were randomized 2:1 to BPX-01 1% or vehicle control once-daily treatment for four weeks. Changes in P. acnes quantitative bacteriological cultures were assessed, as well as cutaneous tolerance to the study drug by both subjects and the investigator. In Study 2 (NCT02815332), subjects with moderate-to-severe inflammatory nonnodular acne (n=226) at 15 centers were randomized 1:1:1 to treatment with BPX-01 1%, BPX-01 2%, or vehicle control once-daily for 12 weeks. The primary endpoint was reduction in the number of inflammatory lesions; other endpoints included the number of noninflammatory lesions, Investigator's Global Assessment (IGA) of severity, and subjective ratings (investigator and subject) of acne. In both studies, cutaneous tolerability and safety were assessed, and plasma minocycline levels were tracked with a highly sensitive assay. Results: In Study 1, BPX-01 treatment reduced P. acnes colonization by 90.9 percent, which exceeded the reduction in the vehicle control group (65.53%; p=0.020). In Study 2, treatment with BPX-01 2% reduced the number of inflammatory lesions by 58.5 percent, exceeding the reduction in the vehicle control group (43.8%; p=0.0256). Trends toward an improvement preferential to BPX-01 2% were observed in the other endpoints. Across both studies, BPX-01 treatment was well-tolerated, with no photosensitivity, postinflammatory hyperpigmentation, or skin discoloration reported. A single subject (out of 259 study participants ) was identified to have detectable levels of plasma minocycline at low levels (42ng/mL) after 12 weeks of treatment but had no signs or symptoms associated with systemic administration of minocycline. Conclusion: BPX-01 appears to exhibit an effectiveness profile for reduction of inflammatory (nonnodular) acne lesions similar to that of oral minocycline formulations. However, because BPX-01 is topical and exhibits negligible systemic exposure, the likelihood of adverse events associated with oral minocycline use is much lower. These results demonstrate effectiveness of BPX-01 topical minocycline gel in reducing P. acnes colonization, suggesting that the BPX-01 2% formulation is a promising treatment for moderate-to-severe nonnodular, inflammatory acne vulgaris in both reduction of inflammatory lesions and also overall improvement in facial acne according to IGA.

Advancing the Care of Post-Acne Scarring: Expert Insights Into New Treatment Options.

Most patients with acne have some degree of facial scarring even after their acne resolves, extending the period of psychosocial distress. Unfortunately, management of acne scars remains challenging. Many treatments for post-acne scarring including chemical peels, skin needling, laser resurfacing, surgical repair, subcision lifting, and punch elevation lifting, are limited by moderate and unpredictable results, significant morbidity, and substantial patient investments in time and money. The most recent addition to the armamentarium is tissue augmentation with soft tissue fillers, including a recently approved polymethylmethacrylate-collagen filler. Matching individual patient needs to the appropriate treatment is crucial. While many patients with acne scars have unrealistic expectations about treatment outcomes, open, honest, and realistic dialogue regarding their treatment options and concerns can facilitate realistic expectations. This article is based on a consensus discussion by the authors, who all have experience managing post-acne scarring, as well as the content of a series of live CME-accredited symposia in connection with major dermatology meetings.

J Drugs Dermatol. 2016;15(5):518-525.

Efficacy and safety of ingenol mebutate 0.015% gel after cryosurgery of actinic keratosis: 12-month results.

INTRODUCTION: Recurrence rates of actinic keratosis (AK) lesions after cryosurgery are high, and this treatment does not address field cancerization. We investigated the efficacy and safety of field treatment of AKs with ingenol mebutate gel following cryosurgery. METHODS: In this phase 3, randomized, double-blind, vehicle-controlled study (NCT01541553), patients ≥18 years with four to eight clinically typical, visible, discrete AKs within a contiguous 25-cm2 treatment area on the face or scalp underwent cryosurgery followed 3 weeks later by once-daily ingenol mebutate 0.015% or vehicle gel for 3 consecutive days. Endpoints included complete clearance at week 11 and safety and efficacy over 12 months. RESULTS: In 329 randomized patients, complete clearance rates were greater with ingenol mebutate than vehicle (week 11: 60.5% vs 49.4%; P=.04; month 12: 30.5% vs 18.5%; P=.01). Fewer patients experienced the emergence of new lesions with ingenol mebutate than with vehicle (38.9% vs 51.9%; P =.02). At month 12, mean percentage reduction of AKs was higher with ingenol mebutate than with vehicle (68.2% vs 54.1%; P =.002). The probability of remaining free of lesions was sustained longer with ingenol mebutate compared with vehicle gel: 78% vs 68% at 6 months; 64% vs 57% at 9 months; 55% vs 40% at month 12, respectively. Ingenol mebutate 0.015% gel was well tolerated and no unexpected adverse events occurred; all adverse events resolved within 2 weeks of starting treatment. CONCLUSIONS: Field treatment with ingenol mebutate 0.015% gel following cryosurgery significantly enhanced clearance of baseline lesions, and was well tolerated. Furthermore, ingenol mebutate 0.015% gel following cryosurgery reduced development of new lesions in the treated field.

Efficacy and safety of ingenol mebutate 0.015% gel 3 weeks after cryosurgery of actinic keratosis: 11-week results.

INTRODUCTION: Cryosurgery is the most common treatment for actinic keratosis (AK) in the United States. Efficacy with cryosurgery is variable, and is a modality for treating individual, visible lesions while failing to treat subclinical lesions. METHODS: FIELD Study 1 (NCT01541553) is a phase 3, multicenter, randomized, double-blind study that evaluated the short- (11-week) and long- (12-month) term efficacy and safety of sequential AK treatment using cryosurgery with liquid nitrogen followed by ingenol mebutate gel, versus cryosurgery followed by vehicle. RESULTS: Overall, 329 patients were randomized to ingenol mebutate 0.015% gel (n=167) or vehicle (n=162) 3 weeks after cryosurgery. Baseline characteristics were balanced across groups. At week 11, complete clearance rate (100%) in the treatment area was higher for ingenol mebutate gel compared with vehicle (60.5% vs 49.4%, respectively; P=.04). Mean percentage reduction in number of AKs versus baseline was also numerically higher for ingenol mebutate gel (82.7% vs 75.6%). A general reduction from baseline lesion count was observed 3 weeks after cryosurgery. Treatment after cryosurgery was well tolerated. CONCLUSIONS: Short-term (11-week) AK clearance rates on the face or scalp with ingenol mebutate gel after cryosurgery were higher than with cryosurgery alone.

Update on facial aging.

Facial aging was once thought to be the result of the relentless downward pull of gravity on skin and underlying fat. In turn, facial fat was believed to be a contiguous sheet of tissue. However, over the past four decades, a number of investigators have examined more closely the causes of facial aging, leading to a better understanding of age-related changes, and have confirmed and further explored the proposal by Gonzalez-Ulloa and Flores in 1965 that facial aging involves changes in muscle and bone, as well as skin and fat. Further, the recent work of Rohrich and Pessa (and other authors) has demonstrated that facial fat is not a sheet of tissue, but rather is compartmentalized throughout the face. This discovery has allowed the evolution of improved techniques for facial rejuvenation.

Nonsurgical modalities to treat the aging face.

Injectable shaping agents include neurotoxins (botulinum toxin type A products), replacement fillers (hyaluronic acid [HA] agents), and biostimulatory fillers (calcium hydroxylapatite [CaHA], polymethylmethacrylate [PMMA], and poly-L-lactic acid [PLLA]). This article presents an overview of the agents currently available for use in facial rejuvenation in the United States.

Surgical versus nonsurgical rejuvenation.

The number of cosmetic procedures for facial rejuvenation has increased steadily over the past decade. The increase in the application of nonsurgical modalities, particularly injectable shaping agents, has been remarkable. As knowledge and experience about facial aging has increased, techniques and tools have improved, and it is increasingly apparent that surgical and nonsurgical/injectable modalities are complementary.

Facial aesthetic analysis.

Consideration of the individual patient's appearance based on systematic mapping and a three-dimensional evaluation of the four levels of facial structure (bone, muscle, fat, and skin) will help the clinician choose the most appropriate modalities for facial rejuvenation. This article addresses these concepts and also discusses universal perceptions of attractiveness.

Appropriate selection and application of nonsurgical facial rejuvenation agents and procedures: panel consensus recommendations.

As injectable products have been introduced and as clinicians have gained experience with them, applications and techniques for injection have evolved, with better cosmetic results, enhanced patient safety, and greatly improved patient satisfaction. Within the past four years, several consensus recommendation panels have been convened to summarize the accumulated clinical experience and knowledge about the application of these products. The guidelines that already exist in the literature are referred to, and suggested guidelines for the administration of poly-L-lactic acid-for which no consensus guidelines have previously been published-are included in this article.

A randomized study of the efficacy and safety of injectable poly-L-lactic acid versus human-based collagen implant in the treatment of nasolabial fold wrinkles.

BACKGROUND: Injectable poly-L-lactic acid (PLLA) is a synthetic, biodegradable, biocompatible polymer device. OBJECTIVE: We sought to compare the efficacy and safety of injectable PLLA with human-derived collagen in treating nasolabial fold wrinkles. METHODS: In this randomized, evaluator-blinded, parallel-group, multicenter study, subjects received injectable PLLA (n = 116) or collagen (n = 117) injections (1-4 visits, 3-week intervals). Wrinkle Assessment Scale scores were calculated at screening; posttreatment week 3; months 3, 6, 9, and 13 (injectable PLLA or collagen groups); and months 19 and 25 (injectable PLLA group). Safety data were obtained from subject interviews and case report forms. RESULTS: Injectable PLLA significantly improved mean Wrinkle Assessment Scale scores (all time points, P < .001). Improvements (up to 25 months after last treatment) were significantly greater (P < .001) than with collagen for posttreatment months 3 to 13. LIMITATIONS: Mostly white women and subjects with Fitzpatrick skin types II and III were included. CONCLUSION: Injectable PLLA provides well-tolerated, effective, and long-lasting (up to 25 months) nasolabial fold wrinkle correction.

Advanced injection techniques of poly-L-lactic acid: a case-based presentation.

This article presents a patient who illustrates the current treatment techniques that optimize the efficacy and tolerability of poly-L-lactic acid.

Longevity of effects of injectable products for soft-tissue augmentation.

With the growing number of injectable products for soft-tissue augmentation, non-surgical total facial restoration is within reach. Nevertheless, the ideal injectable product has yet to be developed; at present different approaches are required for different soft-tissue deficits. Products have previously been categorized as either temporary (requiring frequent touch-up treatments) or permanent (associated with possible long-term complications and results that do not co-exist harmoniously with the aging face). Although this dichotomy remains, longer-lasting or "semi-permanent" products are beginning to emerge. There has long been a void in the availability of products that can effectively rejuvenate the face for between 2 and 5 years. This time period would allow the patient to correct the continuing signs of aging with re-treatment at intervals that are tolerable from both a financial and time-management perspective.

Matching patients with therapy.

Multiple options are available for the treatment of actinic keratosis (AK). Each therapy has its own idiosyncrasies and risks, and not every modality is appropriate for every patient. Physician experience and clinical factors such as patient demographics, concerns, reason for the office visit, and lifestyle, as well as the pros and cons of each treatment modality, must be considered when developing customized rational treatment programs.

Treatment options in the management of actinic keratosis.

Successful treatment of actinic keratosis (AK) requires an understanding of available treatments and matching those treatments with each patient's disease severity, lifestyle, insurance coverage, and primary reason for the physician visit. Cryotherapy and other destructive strategies are optimal for hypertrophic and clearly delineated lesions, but they may not address subclinical lesions and are associated with risk of scarring, infection, and pigmentary changes. Topical therapies such as the fluorouracil creams are appropriate for treating large regions of affected skin but are associated with application-site irritation. A combination of destructive and topical approaches may benefit patients with multiple lesion pathologies.

Fluorouracil 5% and 0.5% creams for the treatment of actinic keratosis: equivalent efficacy with a lower concentration and more convenient dosing schedule.

Several formulations and concentrations of topical fluorouracil have received US Food and Drug Administration (FDA) approval for the treatment of actinic keratosis (AK). The most commonly used are the fluorouracil 5% and 0.5% creams. In clinical trials, these formulations have demonstrated a marked ability to partially and completely eradicate AK lesions. Application site irritation, erythema, and burning are common side effects of both formulations, but comparative data suggest that the fluorouracil 0.5% cream is more cost-effective and may be safer, more tolerable, and as efficacious as fluorouracil 5% cream.