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.

Long-term safety of abobotulinumtoxinA for the treatment of glabellar lines: results from a 36-month, multicenter, open-label extension study.

BACKGROUND: Because abobotulinumtoxinA treatment for glabellar lines must be repeated regularly to prevent recurrence, understanding the safety and effectiveness of long-term, repeated administration of abobotulinumtoxinA is important. OBJECTIVE: To report the long-term safety and efficacy of abobotulinumtoxinA in patients with moderate to severe glabellar lines. METHODS AND MATERIALS: AbobotulinumtoxinA was administered to 1,415 patients in multiple cycles over 24 months as a fixed dose of 50 U or as a dose based on muscle mass and sex (women: 50-70 U; men: 60-80 U). Adverse events were assessed after each visit on days 7, 14, and 30 and monthly thereafter; monitoring continued every 3 months for a total safety monitoring duration of 36 months or less. RESULTS: Nine hundred ninety-one (70%) patients reported treatment-emergent adverse effects (TEAEs); most events were mild (70%) or moderate (20%) in severity. The rate of TEAEs did not increase over 24 months of repeated treatment (mean 5.6 cycles; range 1-9). Treatment-related eyelid ptosis followed 53 of 7,938 (0.7%) treatments, all of which resolved spontaneously. CONCLUSIONS: Multiple cycles of abobotulinumtoxinA treatment over 24 months were well tolerated and effective for the correction of glabellar lines, with no evidence of cumulative safety problems.

Evaluation of an advanced antioxidant and double-conjugated retinoid/AHA cream in participants with FST IV-V.

BACKGROUND: Topical antioxidants and retinoids are foundational components of an effective skincare regimen. Pyrroloquinoline quinone (PQQ) is a potent free radical scavenger that supports efficient mitochondrial energy creation. An advanced antioxidant combines topical allyl PQQ with existing WEL antioxidant technology (TAP) to comprehensively address extrinsic and intrinsic skin aging. In conjunction with TAP, a double-conjugated retinoid/alpha hydroxy acid (AHA-Ret) designed to minimize irritation and optimize delivery was used over 12 weeks to improve the appearance of photodamaged skin. PATIENTS/METHODS: Twice-daily application of TAP and nightly application of AHA-Ret was evaluated in female participants aged 40-65 years with FST IV-V and mild (3) to moderate (6) facial photodamage using a 10-point grading scale. Visible improvements from baseline in lines/wrinkles, skin texture, skin tone, skin dullness and erythema were assessed using a six-point grading scale (0 = None to 5 = Severe). Adverse Events (AEs) were captured throughout the study period. RESULTS: Participants (N = 21; mean age, 56 years) equally represented mild and moderate photodamage, and FST IV and V (41%, Hispanic; 36%, African American; and 32%, Caucasian). Significant mean improvements from baseline occurred in skin dullness, skin texture, and skin tone (all, p < 0.0001), and significant mean reductions from baseline were demonstrated in erythema and melanin at Week 12. Mild, transient AEs were reported. No participant discontinued study participation due to an AE. CONCLUSIONS: A skincare regimen comprised of an advanced antioxidant and AHA-Ret cream, in conjunction with daily use of a broad-spectrum sunscreen (SPF 56), led to significant improvements at 12 weeks in the appearance of photodamaged skin in females with FST IV and V.

A pilot study examining a double-conjugated, retinoid-based skincare regimen for darker, blemish-prone skin.

BACKGROUND: Retinoids and alpha- and beta hydroxy acids are common components utilized in regimens for blemish-prone skin. However, balancing efficacy and tolerability is often challenging. PATIENTS/METHODS: This pilot study evaluated a double-conjugated retinoid serum specifically formulated for blemish-prone skin (AHARet-SA) in combination with exfoliating peel pads (double-conjugated retinoid, glycolic, lactic, and salicylic acids), a cleanser, mineral-based sunscreen, and a lightweight moisturizer in female participants with mild-to-moderate blemish-prone skin. Fifty-five percent of participants were Fitzpatrick Skin Type (FST) IV and 27% were FST V. Participants used the exfoliating peel pads (3x/week for 8 weeks; 2x/week for 4 weeks) followed by nightly AHARet-SA and a moisturizer (as needed). Improvements in skin were assessed using the 5-point Investigator Global Assessment Scale, and participant satisfaction and tolerability were assessed over 12 weeks. RESULTS: Significant mean improvement from baseline in skin clarity occurred after 4 weeks (14%; p = 0.04) with progressive improvements through week 12 (52%; p = 0.004). Eighty-eight percent of participants reported improvements in the appearance and texture of their skin and fewer blemishes/breakouts. Mild, transient adverse events were reported. CONCLUSIONS: A regimen comprised of a double-conjugated serum and exfoliating peel pads formulated for blemish-prone skin led to significant improvements from baseline in skin clarity after 12 weeks in participants with predominately darker skin tones and mild-to-moderate blemish-prone skin.

A Multi-center Trial Evaluating a Serum Comprised of Plant-based Adaptogens Targeting Skin Quality.

Objective: The ability of the skin to maintain homeostasis declines with age. Adaptogens support the capacity of the skin to respond to stress. We sought to evaluate the efficacy of a novel serum comprised of plant-based adaptogens for improving photoaged skin following twice-daily application. Methods: A multi-center, 12-week trial was conducted in participants aged 45 to 65 years, Fitzpatrick Skin Type (FST) I to VI, with mild-to-severe photoaging based on a 10-point grading scale (3 [Minimum] to 7 [Maximum]). Visible improvements were assessed in erythema, pore size, skin dullness, skin texture, and uneven pigmentation utilizing a six-point grading scale (0=None to 5=Severe). Global skin quality was measured utilizing our Global Skin Quality Index (GSQI). Sebum measurements were obtained in a subset of participants. Patient satisfaction and tolerability were recorded throughout the study. Results: Fifty-three participants were enrolled and completed the study. Mean age was 56 years and 66 percent were White, 17 percent were Black, 8 percent were Hispanic, 6 percent were Asian/Pacific Islander, and 81 percent had moderate photodamage. At Week 12, significant mean percent improvements from baseline were demonstrated in erythema (50%), dullness (44%), texture (52%), pore size (23%), and uneven pigmentation (21%; all p<.0001). Significant GSQI improvements from baseline were observed at Week 12 (39%; p<0.0001). Significant mean reductions from baseline in skin surface sebum were demonstrated at Week 12 (-38%; p<0.0001). All adverse events (AEs) were mild and transient. Conclusion: A novel serum comprised of plant-based adaptogens, demonstrated improvements from baseline in the appearance of erythema, dullness, texture, pore size, uneven pigmentation, and global skin quality over 12 weeks. Participants reported high levels of satisfaction, with mild, transient AEs reported.

Gene Expression Analysis of a Topical Serum Comprised of Plant-based Adaptogens Developed to Support Homeostasis and Skin Quality.

Objective: A topical serum comprised of plant-based adaptogens was purposefully developed to support the ability of the skin to adapt and achieve balance. The study described herein evaluated changes in the expression of target genes related to skin homeostasis following topical exposure. Methods: Utilizing an in vitro epidermal skin model, quantitative polymerase chain reaction (qPCR) analysis of gene expression was conducted following 48-hour exposure to 15µL of the study product (MYS serum) to the surface of each tissue (N=4). Biomarkers that play a key role in skin homeostasis were analyzed: Aryl hydrocarbon receptor (AhR), chloride channel accessory 2 (CLCA2), metallothionein 1A (MT1A), 1F (MT1F), and 1G (MT1G), and thioredoxin reductase 1 (TXNRD1). Statistically significant changes were calculated using unpaired t-test analysis (p<0.05) versus control (saline). A linear Fold Change (FC) value >2 was considered statistically significant. Results: An 85 percent (FC=1.85) increase in expression of AhR vs. control occurred following exposure to MYS serum indicating enhanced support of cellular and epidermal homeostasis, and the skin barrier's response to stress. Statistically significant increases in expression occurred with TXNRD1 (293%; FC=3.93), MT1A (307%; FC=4.07), MT1F (529%; FC=6.29), and MT1G (163%; FC=12.63) vs. control, indicating support of skin's adaptive response to stress and immune homeostasis. Significantly decreased levels of CLCA2 were demonstrated (69%; FC=-3.24) indicating inhibition of oxidative stress-induced senescence. Conclusion: Utilizing an in vitro epidermal skin model, a serum comprised of plant-based adaptogens demonstrated changes in the expression of target genes that play important roles in skin's ability to respond to stress and achieve homeostasis.

Systematic review of clinical trials of small- and large-gel-particle hyaluronic acid injectable fillers for aesthetic soft tissue augmentation.

BACKGROUND: Hyaluronic acid (HA) is the most frequently injected filler for soft tissue augmentation in the United States. OBJECTIVE: To systematically review published evidence for aesthetic use of small- and large-gel-particle HA. METHODS AND MATERIALS: Clinical data on anatomic area, level of evidence, patient population, trial design, endpoints, efficacy, and safety were extracted from PubMed. RESULTS: Fifty-three primary clinical reports were analyzed. The highest-quality efficacy evidence was for the nasolabial folds (NLFs), with 10 randomized, blind, split-face, comparative trials. Several randomized, blind trials supported treatment of the glabella, lips, and hands. Lower-level evidence (from studies with nonrandomized, open-label, or retrospective designs) was recorded for the nasojugal folds (tear troughs), upper eyelids, nose, infraorbital hollows, oral commissures, marionette lines, perioral rhytides, temples, and cheeks. Common adverse events (AEs) across anatomic areas were pain, bruising, swelling, and redness. Serious AEs were uncommon (8 events in 8 patients of 4,605 total patients) and were considered to be unrelated (7 events) or probably unrelated (1 event) to treatment. CONCLUSION: The efficacy and safety of small- and large-gel-particle HA are well established for NLFs; evidence for the glabella, lips, and hands is more limited. Preliminary reports in other anatomic regions suggest efficacy without major complications.

Evaluation of a New, Advanced Antioxidant Containing Topical Allyl Pyrroloquinoline Quinone: Analysis of Antioxidant Properties and Visible Effects in Subjects with Facial Photodamage.

Objectives: Evaluate the effects of a new antioxidant containing topical allyl pyrroloquinoline quinone (TAP) on expression of key markers and assess the efficacy and tolerability in subjects with photodamaged skin. Methods: Donor skin tissue was irradiated prior to and following application of study products (TAP; a leading antioxidant cream [L-VC]). Expression of markers related to epidermal homeostasis and oxidative stress were assessed at 48 hours and compared to untreated, irradiated control (n=3 each). Evaluation of lines/wrinkles, skin texture, skin tone, dullness, and erythema from baseline occurred over 12 weeks in subjects with mild-to-moderate photodamaged skin. Histological evaluation occurred at Weeks 6 and 12 (n=4). Results: Following application of TAP, significant expression of markers related to epidermal homeostasis and repair, recycling and removal, and oxidative stress were demonstrated, compared to control (p<0.05). Reduced expression of collagen degrading enzymes, compared to control, were observed (p<0.05). Application of L-VC demonstrated nonsignificant expression of markers versus control. In 40 subjects evaluated over 12 weeks, significant mean improvements from baseline were observed at Week 4 in skin texture and dullness (both p<0.0001) and skin tone and lines/wrinkles (both p=0.01). The study product was highly tolerable. Histologic evaluation demonstrated reductions in solar elastosis from baseline at Weeks 6 (33%, p=0.01) and 12 (60%, p=0.002). Conclusion: An antioxidant containing TAP addresses internal and external manifestations of photoaging. TAP demonstrated significant expression of key markers associated with epidermal homeostasis and counteracting oxidative stress. Significant, early improvements in the appearance of photodamaged skin and histological improvements in solar elastosis were observed.

Efficacy and tolerability of a hyaluronic acid-based serum and a peptide-rich cream for the face and neck in subjects with photodamaged skin.

BACKGROUND: Barrier properties of the stratum corneum inhibit delivery of topical ingredients containing large molecules to desired targets in the skin. This study evaluated the efficacy and tolerability of a skincare regimen comprised of a hyaluronic acid-based serum (InF-HA) and a peptide-rich cream (InF-PEP) containing large molecular ingredients designed to improve the appearance and overall quality of skin. METHODS: This 12-week study evaluated changes from baseline in skin tone, skin texture, and lines/wrinkles (6-point grading scale) of twice-daily application of a two-part skincare regimen to the face and neck in female subjects with mild to moderate photodamage. Subject satisfaction was assessed, and Adverse Events (AEs) were captured throughout. RESULTS: Seventeen subjects with a mean age of 52 years completed the study. Improvements from baseline in the appearance of facial skin texture (79%), lines/wrinkles (50%), and skin tone (44%) occurred at week 12. Improvements in neck appearance from baseline were demonstrated in skin texture (68%), skin tone (48%), and lines/wrinkles (36%). No AEs occurred related to the use of study products. All subjects reported an overall improvement in the appearance of their skin and that their skin looked and felt smoother; 88% reported their skin looked more radiant, and 82% reported their skin looked firmer. CONCLUSIONS: Application of a skincare regimen comprised of an HA-based serum and a peptide-rich cream led to substantial improvements in skin texture, skin tone, and lines/wrinkles on the face and neck over 12 weeks. Both products were well-tolerated with a high level of subject satisfaction.

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.

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.

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.

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.

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.

Addressing treatment challenges in atopic dermatitis with novel topical therapies.

Atopic dermatitis (AD), a chronic inflammatory skin disease affecting children and adults, presents as mild-to-moderate disease in the majority of patients. Pruritus, one of the key diagnostic criteria for AD, is associated with reduced quality of life and disease aggravation. Current treatments include emollients and topical pharmaceutical agents. Topical corticosteroids (TCSs) are commonly used, but are associated with safety concerns with cutaneous and systemic side effects. Topical calcineurin inhibitors (TCIs) inhibit T-lymphocyte activation, but their use is limited because of application-site infections and a boxed warning for potential malignancy risk. Despite recent reports indicating there is no malignancy risk, long-term treatment with TCIs is still considered with hesitancy. In addition, while both TCSs and TCIs provide some relief of pruritus, it often takes over a week for improvement to occur. The development of a more specific anti-inflammatory treatment which is easy to use and targets pruritus could provide clinically meaningful improvements for patients with AD. The majority of emerging therapies for AD are focused on inhibiting phosphodiesterase 4 (PDE4), an enzyme which is increased in inflammatory disorders such as AD. This review will update readers on the recent advances in topical therapies, including PDE4 inhibitors, for the treatment of AD.