Evaluation of a Neck Cream Developed to Enhance Nitric Oxide Availability in Aging Skin.

BACKGROUND: To meet the unique needs of aging skin of the neck, a new neck cream that enhances nitric oxide availability has been developed to visibly improve signs of aging and overall quality of skin. METHODS: The primary objective of this dual center, open label clinical trial was to assess the efficacy and tolerability of the new neck cream applied twice daily over 12 weeks in aging women with mild-to-moderate lines and wrinkles of the neck (Group 1, N=26). A second group with mild-to-moderate lines and wrinkles and photodamage of the neck and décolleté (Group 2, N=10) applied the neck cream (AM/PM) in combination with a double-conjugated retinoid/alpha hydroxy acid (AHA-Ret; PM) to both the neck and décolleté over 12 weeks. RESULTS: Group 1 demonstrated significant improvements from baseline in the neck of 21% (P=.007) for wrinkles and lines, 27% (P=.004) for skin texture, and 26% (P=.003) for skin tone at 12 weeks. Significant improvements were also observed at 4 and 8 weeks. In Group 2, significant improvements were observed from baseline in the neck and décolleté areas with a 34% (P=.01) improvement in photodamaged skin in the décolleté area. The neck cream was well tolerated with few mild and transient adverse events. CONCLUSION: A new neck cream formulated to enhance nitric oxide availability to the skin when applied alone or in combination with AHA-Ret provided statistically significant improvements from baseline in skin appearance of the neck and décolleté, most notably in lines and wrinkles, skin texture, and skin tone. CITATION: Robinson DM, Kaufman J, Giannini A, et al. Evaluation of a neck cream developed to enhance nitric oxide availability in aging skin. J Drugs Dermatol. 2023;22(9):881-886. doi:10.36849/JDD.7210.

Efficacy and Tolerability of a Retinoid Eye Cream for Fine to Moderate Wrinkles of the Periorbital Region.

INTRODUCTION: The periorbital region is susceptible to premature skin aging and among the first areas to manifest age-related changes. Retinoids are highly effective but can be irritating, limiting use in this vulnerable area. A hydrating formulation comprised of a double-conjugated retinoid/alpha hydroxy acid (lactic acid; AHARet-EM) has been developed to address photoaging of the periorbital area. This study evaluated the efficacy, tolerability, and subject satisfaction of nightly application of AHARet-EM, and a regimen that included application of a peptide-rich eye cream (InF-E; AM) and AHARet-EM (PM). DESIGN: A 12-week, dual-center, open-label study evaluated nightly application of AHARet-EM in subjects 35 to 65 years of age with fine to moderate lines/wrinkles in the periorbital area (3-7 score based on the Fitzpatrick Classification Wrinkle Scale [FCWS]). A subset of subjects applied AHARet-EM (PM) and InF-E (AM). Investigator assessments at baseline and weeks 4, 8, and 12 were based on the 9-point FCWS for lines/wrinkles (1 [Fine Wrinkles] to 9 [Deep Wrinkles]) and a 6-point scale (0 [None] to 5 [Severe]) for texture, erythema, and under-eye darkness, puffiness, and dryness. Subject satisfaction and adverse events (AEs) were captured over 12 weeks. RESULTS: Twenty-six subjects, Fitzpatrick skin type III-VI, completed the study. Subjects applying AHARet-EM (n=16) demonstrated significant improvements from baseline at week 12 in the appearance of lines/wrinkles (33%; P<.0001), texture (37%, P<.0001), erythema (37%, P=.004), under-eye darkness (41%; P<.001), puffiness (55%, P<.0001) and dryness (94%, P<.0001). Significant improvements from baseline were demonstrated in subjects using the AM/PM regimen (n=10) at week 12 in the appearance of texture (33%; P=.002), erythema (68%; P=.001), under-eye darkness (32%; P=.007), puffiness (64%; P=.01) and dryness (90%; P<.0001). No AEs occurred related/possibly related to use of the study products. High levels of subject satisfaction were reported over 12 weeks. CONCLUSION: Nightly application of a hydrating, double-conjugated retinoid eye cream demonstrated significant improvements in the appearance of lines/wrinkles, under-eye darkness, puffiness, and dryness of the periorbital area at week 12. Morning application of a peptide-rich eye cream afforded additional benefits. The study products were non-irritating, and subjects reported high levels of satisfaction throughout the study. J Drugs Dermatol. 2022;21(9):932-937. doi:10.36849/JDD.6815.

Efficacy and Tolerability of a Double-Conjugated Retinoid and Alpha Hydroxy Acid Cream in Subjects With Mild to Moderate Blemish-Prone Skin.

BACKGROUND: Topical retinoids influence the rate of cellular turnover and improve skin clarity and photoaged skin. Consequent cutaneous irritation reduces adherence resulting in suboptimal outcomes. A formulation comprised of a double-conjugated molecule containing a retinoid and an alpha hydroxy acid (AHA) has been purposefully developed for individuals with blemish-prone skin. DESIGN AND METHODS: A 12-week study conducted in subjects with mild/moderate blemish-prone skin evaluated skin clarity utilizing the Investigators Global Assessment Scale (0-Clear to 4-Severe). Changes in the appearance of pores were evaluated using a 6-point scale (0-None to 5-Severe). Adverse Events (AEs) and subject satisfaction were captured. A secondary analysis evaluated visible, quantitative changes in pores. RESULTS: Twenty subjects enrolled; 19 subjects completed the study. Mean percent improvements in appearance from baseline in skin clarity were demonstrated at weeks 4 (43%; P<.0001), 8 (48%; P<.0001) and 12 (50%; P<.0001). Mean percent visible improvements from baseline in pores were observed at 4, 8, and 12 weeks (33% [P<.0001]; 21% [P=.04] and 25% [P=.0006], respectively). AEs were mild and transient. By 8 weeks, all subjects reported improvement in overall appearance and that their skin was healthier looking. Secondary quantitative analysis (n=6) demonstrated an 18% mean improvement in the appearance of pores from baseline at week 12. CONCLUSIONS: A double-conjugated retinoid/AHA cream specifically developed for individuals with blemish-prone skin demonstrated early improvements in the appearance of skin clarity and pores over 12 weeks. AEs were mild and transient. Subjects reported high levels of satisfaction in the overall appearance and quality of skin. J Drugs Dermatol. 2022;21(1):54-59. doi:10.36849/JDD.6415.

A pilot study evaluating the efficacy and tolerability of a comprehensive, hydrating topical antioxidant developed specifically for men.

INTRODUCTION: There is growing interest in skincare products designed for men. This pilot study evaluated the efficacy and tolerability of a comprehensive antioxidant product in men. METHODS: This 12-week study evaluated improvements from baseline in erythema, lines/wrinkles, skin tone, texture, brightness, dryness/flaking and pores (6-point scale), global improvements (5-point scale), and sebum levels following daily application in males with mild to moderate photodamaged skin. Subject self-assessments and adverse events (AEs) were captured. RESULTS: Twenty-two subjects completed the study. Early mean percent improvements from baseline were demonstrated in all categories at week 4 with visible improvements in skin tone (29%; p = .0001) and pores (28%; p < .0001). Reductions in skin surface sebum levels (forehead region) from baseline were demonstrated at 8 (p < .0001) and 12 (p < .0003) weeks. Ninety-six percent of subjects reported overall visible improvement of their skin and that the study product calmed/soothed skin, reducing redness and irritation after shaving. One subject reported mild dryness. CONCLUSION: Once daily application of a comprehensive topical antioxidant designed for men led to significant improvements in skin appearance, substantial reductions in skin surface sebum levels, and was well tolerated with a high level of subject satisfaction over 12 weeks.

A comprehensive topical antioxidant inhibits oxidative stress induced by blue light exposure and cigarette smoke in human skin tissue.

OBJECTIVE: Skin damage from visible light predominantly results from exposure to the blue light spectrum (400-500 nm) which generates Reactive Oxygen Species (ROS) causing a cascade of harmful effects to skin. Topical antioxidants reduce the effects of free radical damage caused by environmental exposures. This study evaluated a comprehensive topical antioxidant's ability to inhibit ROS production induced by blue light and cigarette smoke (CS) in human skin. METHODS: Two experiments were conducted utilizing human skin (Fitzpatrick Skin Types III and V; N = 3, each). After confirmed reactivity of untreated tissues at 412 nm, 20J/cm2 , untreated and pretreated (WEL-DS, 2 mg/cm2 ) skin tissue was exposed to blue light and blue light plus CS and left overnight. A nonfluorescent probe (DCFH-DA) was added to skin and exposed to blue light (412 nm, 20J/cm2 ) and blue light plus CS. Fluorescent 2',7'-DCF was generated upon enzymatic reduction and subsequent oxidation by ROS. RESULTS: ROS increased at least tenfold following initial exposure to blue light and blue light plus CS in untreated skin. Pretreatment with WEL-DS decreased ROS in FST III exposed to blue light by 51% and 46% in skin exposed to blue light plus CS vs. untreated skin (both, P < .001). In FST V, pretreatment with WEL-DS decreased ROS exposed to blue light by 54% (P < .001) and 50% in skin exposed to blue light plus CS vs. untreated skin (P < .0001). CONCLUSION: WEL-DS demonstrated significant reduction in ROS induced by blue light and blue light in combination with CS compared with untreated, exposed skin.

Protective effects of a comprehensive topical antioxidant against ozone-induced damage in a reconstructed human skin model.

Tropospheric ozone (O3) is a source of oxidative stress. This study examined the ability of a topical antioxidant (WEL-DS) to inhibit O3-mediated damage in a human epidermal skin model. Four groups of tissues (N = 24) were compared: Group 1 (control) were untreated and unexposed; Group 2 were untreated and exposed to O3 (0.4 ppm, 4 h); Group 3 were pretreated with WEL-DS and unexposed; Group 4 were pretreated with WEL-DS and exposed to O3 (0.4 ppm, 4 h). Pretreated tissues were topically treated with 20 uL of WEL-DS and incubated for up to 20 h at 37 °C [humidified, 5% carbon dioxide (CO2)]. After 24 h, tissues were re-treated with WEL-DS and exposed to O3. Tissues were evaluated for Reactive Oxygen Species (ROS), hydrogen peroxide (H2O2), 4-hydroxynonenal (4-HNE) protein adducts, NF-κB p65 response and histology. In O3-exposed groups, WEL-DS significantly inhibited ROS formation vs. untreated tissues (p < 0.05). Pretreatment with WEL-DS inhibited H2O2 production vs. untreated tissues (p < 0.05), and decreased NF-κB p65 transcription factor signal. Oxidative stress induction in O3-exposed tissues was confirmed by increased levels of 4-HNE protein adducts (marker of lipid peroxidation); WEL-DS application reduced this effect. WEL-DS inhibited damage in tissues exposed to O3 with no significant changes in epidermal structure. A comprehensive topical antioxidant significantly diminished O3-induced oxidative damage in a human epidermal skin model.

In vitro and in vivo evaluation of a moisture treatment cream containing three critical elements of natural skin moisturization.

OBJECTIVES: To evaluate skin barrier and hydration effects of a new rebalancing moisture treatment (TRMT) and to assess efficacy and tolerability in subjects with photodamaged skin. METHODS: In an epidermal skin model, tissues (n = 5/group) were topically treated with 25 µL of TRMT, 25 µL of a market-leading moisturizer (MLM), or untreated for 60 minutes. Hydration was measured at 0, 15, and 30 minutes. Tissues were harvested for gene expression analysis of markers associated with skin barrier and hydration: Claudin (CLD), Aquaporin (AQP), Hyaluronic Acid Syntheses (HAS), and Hyaluronidase (HYAL). A clinical study evaluated twice-daily application of TRMT, assessing changes in fine lines/wrinkles, brightness, texture, erythema, and tolerability from baseline through week 8. Hydration was measured using electrical impedance. RESULTS: TRMT and MLM demonstrated significant increases in hydration vs untreated tissue at each timepoint (P < .005), with greater hydration effects observed for TRMT vs MLM. TRMT-treated tissues demonstrated greater expression of CLD, AQP, and HA, and reduced expression of HYAL vs untreated and MLM-treated tissues. Twice-daily application of TRMT demonstrated significant improvements at 2 weeks in fine lines/wrinkles (P < .001), brightness (P < .0001), texture (P < .0004), and hydration (P < .004). At 8 weeks, statistically significant improvements were achieved in all categories. CONCLUSION: In an epidermal skin model, TRMT demonstrated significant increases in hydration, greater hydration effects, and expression of key markers associated with skin barrier and hydration vs a MLM. Twice-daily application of TRMT was well tolerated and resulted in early, significant improvements in hydration and visible improvements in skin brightness, texture, fine lines/wrinkles, and erythema at 8 weeks.

In Vitro and In Vivo Efficacy and Tolerability of a Non-Hydroquinone, Multi-Action Skin Tone Correcting Cream

Background: Pigmentation disorders are therapeutically challenging to treat, requiring complicated regimens. Objectives: Alternatives to hydroquinone (HQ) are desired. We evaluated the efficacy and tolerability of a non-HQ multi-action skin tone corrector (ETCS) developed to inhibit melanin production and improve skin quality. Design and Methods: Twice-daily use of ETCS and ETCS + AHA-Ret, a retinoid-based alpha hydroxy acid cream, was evaluated in subjects with mild to severe dyschromia. Digital images were obtained at baseline, 4, 8, and 12 weeks and included assessment of dyschromia, erythema, fine lines/wrinkles, pores, texture, and global improvement. Melanin Index (MI) measurements were obtained at baseline, 4, 8, and 12 weeks. Subject self-assessments were obtained over the course of the study. Adverse Events (AEs) were collected throughout the study. An extension study evaluated use over 16-weeks. Results: Significant mean reductions from baseline occurred in dyschromia for ETCS (n=42) and ETCS + AHA-Ret (n=10) over 12 weeks (P<0.0001, each). Significant mean reductions from baseline in MI were achieved in both groups at every timepoint (ETCS: P<0.0001; ETCS + AHA-Ret: P<0.02, 4 weeks; P<0.0001, 8 and 12 weeks). Substantial improvements were demonstrated in global improvement, fine lines/wrinkles, erythema, pores, and texture at 12 weeks. Reductions from baseline occurred in dyschromia and MI (P<0.0001, each) at 16 weeks. High levels of subject satisfaction were reported with nearly all subjects reporting reduced appearance of uneven skin tone/discoloration and lightened darker patches, and improvement in overall skin tone. Mild, transient AEs were reported with no discontinuations due to an AE. Conclusions: Twice daily use of ETCS led to early, significant reductions in dyschromia and melanin index. Combination use with a retinoid-based, AHA cream in the evening demonstrated enhanced reductions. ETCS effectively reduced hyperpigmentation, improved overall skin appearance, and was highly tolerable. J Drugs Dermatol. 2019;18(7):642-648.

Evaluation of the Antioxidant Capacity and Protective Effects of a Comprehensive Topical Antioxidant Containing Water-soluble, Enzymatic, and Lipid-soluble Antioxidants.

Objectives: Investigators sought to evaluate the antioxidant capacity of a comprehensive topical antioxidant (WEL-DS), its ability to protect skin against the oxidizing effects of UVA/UVB radiation, and to assess the effectiveness and tolerability of WEL-DS for visible improvements in facial photodamage. Study Designs: In-vitro testing utilized a hydrogen peroxide assay to detect activity in human skin explants following application with WEL-DS, a leading antioxidant serum (L-AOX), and a saline control. Clinical studies included a minimal erythema dose (MED) trial in female subjects, aged 35 to 60 years. Skin was initially irradiated to determine each subject's MED. WEL-DS was applied for four days to one site on the lower back of subjects; the other site remained untreated. Both sites were irradiated with 1X, 2X and 3X each subject's MED, digital images were obtained, and punch biopsies were collected from the 3X MED irradiated areas for histological analysis. A second clinical study evaluated efficacy and tolerability of twice daily application of WEL-DS in female subjects, aged 25 to 65 years with mild-to-moderate photodamage. Changes in fine lines/ wrinkles, dyschromia, erythema, skin tone, pores, and tolerability were assessed at baseline and Weeks 4, 8, and 12. A subset of subjects were evaluated through Week 16. Results: Skin treated with WEL-DS neutralized up to 53 percent more oxidative stress relative to L-AOX. WEL-DS-treated skin demonstrated significantly less UV-induced erythema at 1X, 2X, and 3X MED and demonstrated cellular protective effects versus untreated irradiated skin (N=5). WEL-DS demonstrated average improvements from baseline of 37 percent, fine lines/ wrinkles; 17 percent, skin tone; 13 percent, dyschromia; 18 percent, erythema; and four percent, pores (N=21; Week 12). Continued improvements were demonstrated in all parameters in an extension study (n=14; week 16). WEL-DS was well-tolerated. Conclusion: These studies demonstrate WEL-DS's innate ability to quench free radicals, protect skin from the oxidizing effects of UV radiation, and reduce the visible effects of facial photodamage.

Efficacy and tolerability of a double-conjugated retinoid cream vs 1.0% retinol cream or 0.025% tretinoin cream in subjects with mild to severe photoaging.

BACKGROUND: Topical retinoids are used to treat the visible signs of photoaging. While efficacious, they are irritating. OBJECTIVE: Evaluate the effectiveness and tolerability of a double-conjugate retinoid cream (AlphaRet Overnight Cream; AHA-Ret) in improving visible signs of photoaging vs 1.0% retinol or 0.025% tretinoin. METHODS: A 12-week, split-face, randomized trial was conducted in 48 female subjects, aged 30-65 years with mild to severe photodamage. AHA-Ret was applied to one side of the face and either retinol (n=24) or tretinoin (n=24) to the other side (PM). Expert blinded evaluation of images and Nova measurements occurred at 4, 8, and 12 weeks. Tolerability was assessed throughout the study. RESULTS: Forty-seven subjects completed the study. AHA-Ret demonstrated significant reductions in average severity from baseline: Fine Lines/Wrinkles (P<.001; all time points); Erythema (P=.004, P<.0001; 8 and 12 weeks, respectively); Dyschromia (P<.0001; all time points); Skin Tone (P<.0001; all time points), and Pore Size (P=.035, P<.0001; 8 and 12 weeks, respectively). AHA-Ret induced less Erythema vs retinol at 8 (P=.008) and 12 (P<.02) weeks. AHA-Ret was noninferior to prescription tretinoin in all categories at 4 and 8 weeks, and for Fine Lines/Wrinkles, Erythema, Dyschromia, and Skin Tone at 12 weeks. Improvements in Hydration occurred at every time point with AHA-Ret only (P<.04, P<.03, P<.01). Less irritation was reported with AHA-Ret vs retinol or tretinoin. CONCLUSIONS: Treatment with a double-conjugate retinoid cream demonstrated early reductions in photodamage and improvements in Hydration. AHA-Ret induced less Erythema vs retinol and was more tolerable vs retinol and tretinoin.

Current aesthetic use of abobotulinumtoxinA in clinical practice: an evidence-based consensus review.

The amount and complexity of scientific and clinical evidence for aesthetic use of botulinum neurotoxin type A (BoNT-A) has expanded rapidly in recent years, especially for abobotulinumtoxinA, necessitating reassessment of current knowledge about aesthetic use of abobotulinumtoxinA and other BoNT-A preparations. A committee of 13 plastic surgeons, facial plastic surgeons, and dermatologists engaged in a live discussion of information from a systematic literature review and an Internet-based survey of their beliefs and practices. The committee achieved consensus on most issues. It was concluded that doses of different BoNT-A preparations cannot be interconverted with a fixed ratio. The size of the "field of effect" is difficult to measure, and comparisons between preparations have yielded equivocal results. Nonresponse due to neutralizing antibodies appears exceedingly rare with currently available BoNT-A preparations and of little concern clinically. BoNT-A dose, injection depth, and injection technique should be adjusted according to the anatomic area being treated and each patient's individual characteristics and goals. Aesthetic use of BoNT-A has a good safety profile. Most adverse events are minor and related to the trauma of injection, although special care is needed in certain anatomic areas. Detailed recommendations for treatment of different anatomic areas are presented. BoNT-A products are often used in conjunction with other treatment modalities (eg, fillers and resurfacing), but little agreement was reached on best practices. The findings reported in this consensus document may serve as a practical guide for aesthetic practitioners as they apply the latest knowledge about BoNT-A in providing their patients with optimal care.

Rheological evaluation of the physical properties of hyaluronic acid dermal fillers.

BACKGROUND: Hyaluronic acid (HA) gels are commonly injected into the skin to lift rhytides and to improve facial appearance. The different processes used in their manufacture and formulation yield products with unique physical characteristics that play an important role in predicting their clinical performance. OBJECTIVE: The following rheologic evaluation was performed to objectively measure the physical characteristics of HA dermal filler products derived from similar bacterial sources and containing the same butanediol diglycidyl ether cross-linker, but formulated using different manufacturing techniques. The objective of this study was to evaluate the physical characteristics of two distinct families of HA products, thereby providing clinicians with a greater understanding of these products' attributes and the ability to optimize their use in the treatment of patients seeking facial rejuvenation. MATERIALS AND METHODS: The physical properties of commercially-available dermal fillers containing HA were evaluated using rheologic testing methods under clinically-relevant conditions. Additionally, light microscopy was used to assess the particulate nature of each product. RESULTS: The gels tested demonstrated a broad range of elasticity, firmness and viscosity. Light microscopy confirmed the particulate nature of each product and revealed HA particles of varying size and distribution. CONCLUSION: This rheologic evaluation demonstrates that differences exist among the HA products tested including gel elasticity, viscosity, and the range and distribution of gel particle sizes. Understanding the distinct physical characteristics of different HA dermal fillers and how these characteristics may predict their clinical behavior can assist clinicians in achieving the desired results in patients seeking facial rejuvenation.

The science and manufacturing behind botulinum neurotoxin type A-ABO in clinical use.

BACKGROUND: Since the first comprehensive description of the physiologic effects of botulism toxicity in the 1820s, specific formulations of botulinum neurotoxin type A (BoNT-A) have been developed. Now, a new botulinum neurotoxin type A formulation (BoNTA-ABO; Dysport [abobotulinumtoxinA]; Medicis Aesthetics, Scottsdale, AZ) has been made available in the United States and these same physiologic effects have become beneficial clinical targets. This formulation has been used successfully for nearly 20 years in Europe and other countries under the trade name Dysport (Clostridium botulinum type A toxin-hemagglutinin complex; Ipsen Biopharm, Wrexham, UK). BoNT-A injections are administered to achieve temporary local flaccid paralysis of targeted muscles. Injection of BoNT-A formulations for aesthetic purposes was by far the most common minimally-invasive (nonsurgical) cosmetic procedure performed in the United States in 2008. OBJECTIVE: The objective of this review is to describe the latest data regarding the mechanism of action of BoNTA-ABO, the potential roles of neurotoxin-associated proteins (NAP), the manufacturing standards for these biologic products, and the specific manufacturing process and characteristics of BoNTA-ABO. METHODS: A systematic search using the US National Library of Medicine PubMed database was performed and the relevant articles were reviewed. Direct input and data from the worldwide manufacturer of Dysport have been included. RESULTS: The four sequential steps in the mechanism of action of BoNTA-ABO are binding, internalization, translocation, and intracellular proteolysis of the target protein. Although all BoNT-A products must meet standards for quality, potency, and safety, they should not be considered equivalent formulations because they have different production strains of the bacterium C botulinum, as well as different isolation and manufacturing processes that result in unique product characteristics. The production steps for Dysport-including a unique proprietary purification process using column chromatography and a unique proprietary finishing process-result in consistent and unique product features. Studies confirm that Dysport has a high degree of long-term batch-to-batch consistency for a range of specified properties, including specific potency, protein composition, toxin complex charge-density properties, and endopeptidase activity. In the native, natural form, NAP protect the endogenous neurotoxin from degradation in the acidic environment of the stomach; in biologic formulations, they may have effects on the structural stability, binding, uptake, and transcytosis of BoNT-A products in other areas of the body. NAP are most likely to stabilize the neurotoxin in a vial of clinical product. CONCLUSIONS: A thorough understanding of the mechanism of action, product characteristics, and effects of NAP is important to ensure appropriate and safe clinical use of BoNT-A products. Now approved in the United States, Dysport is an important addition to the group of available BoNT-A formulations.

A novel gel formulation of 0.25% tretinoin and 1.2% clindamycin phosphate: efficacy in acne vulgaris patients aged 12 to 18 years.

Treatments for mild to moderately severe acne usually combine retinoid and antimicrobial therapy. Recently, the US FDA approved the combination of 1.2% clindamycin (CLIN) and 0.025% tretinoin (RA) in a novel gel formulation for the treatment of mild to moderate acne, based on results from two 12-week, multicenter, double-blind Phase 3 trials in which patients were randomized to four treatment arms: CLIN/RA, CLIN, RA, and vehicle. The trials studied more than 4500 patients 12 years of age or older. In both trials, CLIN/RA gel produced significantly greater clinical improvements than vehicle or either monotherapy. CLIN/RA was safe and well tolerated in both trials and in a 52-week safety follow-up evaluation. The current study is a subgroup analysis that evaluates CLIN/RA's effects on acne lesion prevalence in 12- to 18-year-old patients with mild to severe baseline acne severity. CLIN/RA significantly reduced the number of inflammatory, noninflammatory, and total acne lesions after 12 weeks of treatment (p < or = 0.004) in 1,710 patients aged 12 to 18 years. Relatively greater improvements were seen following CLIN/RA treatment compared to CLIN or RA monotherapy, or the vehicle gel beginning as early as 2 weeks following treatment initiation. This novel CLIN/RA gel for treating acne is tolerable and safe and offers clinicians and teen aged patients a new and efficacious intervention for acne vulgaris.

Tolerability of clindamycin/tretinoin gel vs. tretinoin microsphere gel and adapalene gel.

BACKGROUND: Newer agents and formulations seek to improve the tolerability of topical retinoid therapy. Recently, a gel containing crystalline clindamycin 1.2% and tretinoin 0.025% (CLIN/RA) was approved by the U.S. Food and Drug Administration (FDA) for the treatment of treating mild-to-moderate acne. OBJECTIVE: This single-center, randomized, evaluator-blind phase 1 study compared the tolerability of CLIN/RA to 0.1% tretinoin gel or 0.1% adapalene gel. RESULTS: Forty-five patients applied CLIN/RA once daily to one side of their face every day for 21 days. Patients were randomized to either tretinoin 0.1% (n = 23) or adapalene 0.1% (n = 22) on the contralateral side. A clinical evaluator assessed degree of erythema and scaling; patients provided subjective evaluations of burning, stinging, and itching. CONCLUSION: CLIN/RA was significantly better tolerated than was 0.1% tretinoin gel, as evidenced by significantly reduced erythema (P < 0.04), scaling (P < 0.03), itching (P < 0.02), burning (P < 0.03) and stinging (P < 0.04). A trend for greater erythema, scaling, and subjective discomfort for 0.1% adapalene gel compared to CLIN/RA was also evident.

Safety of a novel gel formulation of clindamycin phosphate 1.2%-tretinoin 0.025%: results from a 52-week open-label study.

Acne affects as many as 50 million individuals in the United States. Topical therapy combining a retinoid and an antibiotic is recommended as a first-line therapeutic option for mild to moderately severe acne. Although treatment for extended durations may be required, little long-term safety data on these combination therapies are available. This report summarizes the long-term safety and tolerability of a novel combination product for the treatment of acne vulgaris in participants 12 years and older. The combination treatment is a gel formulation containing a crystalline suspension of clindamycin phosphate 1.2%-tretinoin 0.025% (CLIN/RA). Two cohorts participated in a long-term (up to 52 weeks), multicenter, open-label, safety evaluation of CLIN/RA. Treatment duration was 6 months for the first cohort (N = 442) and 12 months for the second cohort (N = 213). Overall, the CLIN/RA gel was well-tolerated; 92%, 91%, and 94% of participants reported no itching, burning, or stinging, respectively. The most frequent adverse events were acne (29/442; 7% [usually a flare]), sunburn (12/442; 3%), hypersensitivity (7/442; 2%), contact dermatitis (5/442; 1%), and application-site desquamation (3/442; 1%). These results confirm the safety of CLIN/RA gel for mild to moderately severe acne. The CLIN/RA gel fixed-dose combination provided minimal adverse events and a favorable safety profile for 2 agents with established efficacy for the treatment of acne vulgaris.

A novel gel formulation of clindamycin phosphate-tretinoin is not associated with acne flaring.

Concern exists about using topical retinoids on patients with inflammatory acne lesions, fearing that a flare in inflammation will occur. In 3 multicenter, double-blind, randomized, phase 3 trials of a clindamycin phosphate 1.2%-tretinoin 0.025% gel (CLIN/RA), clinical evaluations after 2 weeks of treatment determined if flaring occurred in participants treated with tretinoin gel 0.025% (RA) monotherapy, and the difference in inflammation when treated with the combination formulation. Flaring was assessed as an increase in inflammatory lesions of 10% or greater or 20% or greater versus baseline. Most participants experienced improvement in lesions across treatment groups. Participants with mild acne at baseline treated with RA monotherapy had significantly higher rates of flaring compared with participants treated with vehicle gel (VEH) (P < .001). Treatment with CLIN/RA or clindamycin phosphate gel 1.2% (CLIN) monotherapy resulted in significantly lower rates of flaring than RA or VEH (P < .001 for all). Participants with moderate to severe acne showed no signs of RA-induced flaring. In each comparison, the CLIN/RA combination showed the lowest percentage of increased inflammatory lesions. These results indicate that RA-induced flaring may occur with mild inflammation; combining RA with CLIN prevents this flaring. Participants with moderate to severe inflammatory acne did not show an increase in inflammatory lesions compared with participants treated with VEH. Lack of flaring may result from either the novel vehicle formulation or the antiinflammatory effects of CLIN.

Antibiotic-resistant Propionibacterium acnes suppressed by a benzoyl peroxide cleanser 6%.

Adding topical benzoyl peroxide (BPO) to antibiotics can reduce resistant Propionibacterium acnes in patients with acne receiving antibiotic therapy. Benzoyl peroxide often is formulated as a wash, but no published data exist regarding BPO wash formulation efficacy in reducing resistant strains of P acnes. This 3-week, open-label, single-center study evaluated the effects of BPO cleanser 6% on antibiotic-resistant P acnes populations. The study involved 30 healthy adults who were free of acne but had high facial P acnes populations (10,000 colonies/cm2 or more) resistant to erythromycin and tetracycline at 8 microg/mL or more and 2 microg/mL or more, respectively. Participants applied BPO cleanser 6% once daily. Quantitative P acnes cultures were obtained at baseline and weekly for 3 weeks. At baseline, resistance to erythromycin, tetracycline, doxycycline, minocycline, and clindamycin was present in 100% (30/30), 97% (29/30), 83% (25/30), 63% (19/30), and 100% (25/25) of participants, respectively, high-level resistance for erythromycin and tetracyclines and intermediate to high resistance for clindamycin was present in 100% (30/30), 50% (15/30), 33% (10/30), 27% (8/30), and 52% (13/25) of participants, respectively. Total P acnes counts and counts of each resistant strain decreased by approximately 1 log after 1 week of treatment, by at least 1.5 log after 2 weeks of treatment, and by at least 2 log after 3 weeks of treatment, with no differences between resistant and susceptible strains or between highly resistant and low-level resistant strains. Benzoyl peroxide cleanser 6% effectively reduced resistant P acnes populations and offers a useful therapy for controlling antibiotic resistance in patients receiving antibiotics.

Clinical safety and efficacy studies of a novel formulation combining 1.2% clindamycin phosphate and 0.025% tretinoin for the treatment of acne vulgaris.

Clindamycin phosphate 1.2% and tretinoin 0.025% gel (CLIN/RA gel [ZIANA Gel]) is a novel topical combination agent approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older. A solution of clindamycin phosphate 1.2% combined with partially solubilized and crystalline tretinoin 0.025% suspended in an aqueous-based, alcohol-free gel formulation, CLIN/RA gel was studied in 2 randomized, vehicle-controlled trials involving more than 4,500 patients. Efficacy results from these studies showed that treatment with the combination significantly reduced lesion counts and improved patients' overall appearance to a greater extent than the individual components. Individual ingredients and the combination were well-tolerated. Among those treated with the combination formulation, discontinuation rates due to adverse events were 1% or less.