The Awareness of and Adherence to the Pregnancy Prevention Program for Oral Retinoids: A Questionnaire Survey in Denmark.

PURPOSE: We aimed to investigate the awareness of oral retinoid teratogenicity and the adherence to the pregnancy prevention program (PPP) related to oral retinoid use by physicians, pharmacists, and patients in Denmark. METHODS: As part of the multi-country survey, web-based questionnaires were distributed among Danish dermatologists, general practitioners, community pharmacists, and women of childbearing age, who were using or had used oral retinoids within the past 5 years. RESULTS: A total of 62 physicians, 96 pharmacists, and 50 oral retinoid using women responded; 95%, 100%, and 98%, respectively, were aware of the teratogenic risks of oral retinoids. For physicians, the most applied PPP measures were the usage of the patient (44%) and the healthcare professional (19%) guides, while the least applied measure was signing medication risk awareness form (3%). Among the pharmacists, the warning sign on the outer medication package was the most used measure (45%). Among the women, a majority (90%) had read the patient information leaflet included in the medication package and 72% discussed the use of contraception with their healthcare provider, while risk awareness forms and patient cards were seen by only few. CONCLUSIONS: In Denmark, physicians, pharmacists, and medicine users were aware about the teratogenic effects of oral retinoids. Adherence to pregnancy prevention measures varied, suggesting unwillingness to use the measures that require patients' signatures among physicians and a lack of awareness of pharmacy targeting measures. Accessibility of the latter measures need to be optimized to improve the safety of oral retinoid use.

Adverse Pregnancy and Child Outcomes in Oral Retinoid-Exposed Pregnancies: A Nationwide Population-Based Study.

BACKGROUND: Oral retinoids are used to treat various dermatological conditions, and their use is increasing in women of childbearing age. However, there is limited knowledge on the incidence of adverse outcomes after retinoid exposure during pregnancy. We aimed to evaluate the risk of adverse outcomes associated with oral retinoid exposure during pregnancy. METHODS: We conducted a retrospective cohort study using the NHIS mother-child linked healthcare database in South Korea. We included all women who gave live birth from April 1, 2009 to December 31, 2020 and their children. The exposure was defined as having ≥ 1 prescription of isotretinoin, alitretinoin, and acitretin from one month before pregnancy to the delivery. The outcomes of interest were adverse child outcomes including major congenital malformations, low birth weight, and neurodevelopmental disorders (autism spectrum disorder and intellectual disorder), and adverse pregnancy outcomes including gestational diabetes mellitus, preeclampsia, and postpartum hemorrhage. Propensity score-based matching weights were used to control for various potential confounders. For congenital malformation, low birth weight, and adverse pregnancy outcomes, we calculated relative risk (RR) with 95% confidence interval (CI) using a generalized linear model and for neurodevelopmental disorders, we estimated hazard ratio (HR) with 95% CI using the Cox proportional hazard model. RESULTS: Of 3,894,184 pregnancies, we identified 720 pregnancies (0.02%) as the oral retinoid-exposed group. The incidence of major congenital malformation was 400.6 per 10,000 births for oral retinoid-exposed group and 357.9 per 10,000 births for unexposed group and the weighted RR was 1.10 (95% CI, 0.65-1.85) in oral retinoid-exposed group compared with unexposed group. The neurodevelopmental disorder showed a potential increased risk, with the weighted HR of 1.63 (95% CI, 0.60-4.41) for autism spectrum disorder and 1.71 (95% CI, 0.60-4.93) for the intellectual disorder, although it did not reach statistical significance. For low birth weight and adverse pregnancy outcomes, no association was observed with oral retinoid exposure during pregnancy. CONCLUSION: This study found no significantly increased risk of congenital malformations, autism spectrum disorders, and intellectual disability associated with oral retinoid exposure during pregnancy; however, given the limitations such as including only the live births and increased point estimate, potential risk cannot be fully excluded.

[Translated article] Iberia Consensus on Strategies to Prevent and Manage Irritation by Topical Retinoids in Facial and Trunk Acne.

OBJECTIVE: To assess the level of agreement on various prevention and management strategies for irritation caused by topical retinoids in facial and trunk acne in an attempt to alleviate it and minimize treatment discontinuations as much as possible. METHOD: After reviewing the scientific medical literatura currently available, 4 different areas of uncertainty in the management of irritation caused by topical retinoids in acne were identified. A questionnaire with 34 recommendations was created and evaluated by a group of 133 dermatologists (Delphi methodology). RESULTS: In 82.3% of the recommendations (28 out of 34), some level of agreement was reached (≥85% agreement in 22 recommendations and≥70% agreement in 6). The results with the highest level of agreement focused on specific patient education strategies (explaining that irritation is an expected reaction at the beginning of treatment and tends to decrease over time), gradual and/or spaced application of topical retinoids (at night time to prevent and/or reduce skin irritation), and the importance of using adjuvant products, specific for acne-prone skin, hydration, photoprotection, and skin cleansing. These recommendations reflect a comprehensive approach to managing irritation associated with topical retinoids and promoting long-term adherence. CONCLUSIONS: Skin irritation caused by topical retinoids in facial and trunk acne is an expected, mild, and controllable reaction if proper prevention and management guidelines are followed, meaning that it should not be a reason for treatment discontinuation.

Topical Treatments for Photoaged Skin.

BACKGROUND: Photoaging due to cumulative lifetime ultraviolet light exposure is the greatest contributing factor to facial aging. With the continued growth of the population of individuals aged ≥65 years and over, demand for safe and effective photoaging treatments will likely increase. METHODS: This qualitative review provides an overview of efficacy and safety of over-the-counter (OTC) and prescription topical treatments for photoaging, including recent data from an investigator-initiated trial of the topical retinoid tazarotene. RESULTS: OTC and cosmeceutical products comprise the majority of treatment options for photoaging, although clinical data in support of their efficacy are generally lacking. Topical retinoids have been shown to increase collagen and elastic fibers and normalize melanocytes and keratinocytes, yielding improvements in wrinkling, texture, elasticity, and skin tone. Prescription topical retinoids (adapalene, tazarotene, tretinoin) are the most studied and efficacious treatments for photoaging, though their use is typically associated with adverse effects such as erythema, peeling, dryness, and burning/stinging in a concentration-dependent manner. In a 12-week, open-label study, lower-dose tazarotene 0.045% lotion led to significantly reduced signs and severity of photoaging vs baseline. CONCLUSION: Prescription topical retinoids are the most potent treatment option for photoaging, though their use may be limited by irritation concerns. Tazarotene 0.045% polymeric emulsion lotion has recently demonstrated significant photoaging improvements with 12 weeks of once-daily treatment, with a favorable safety and tolerability profile. CITATION: Sadick N, Pannu S, Abidi Z, et al. Topical treatments for photoaged skin. J Drugs Dermatol. 2023;22(9):867-873. doi:10.36849/JDD.7753.

Topical Treatments for Melasma and Post-inflammatory Hyperpigmentation.

BACKGROUND: Dyschromia is one of the most common reasons for patients to seek dermatological care, especially among individuals with skin of color. Most cases present as melasma or post-inflammatory hyperpigmentation (PIH); both are chronic issues requiring long-term treatment. While many pharmaceutical (topical or systemic) or procedural (lasers/chemical peels) options are available, some treatments are not safe/tolerable for long-term use or can induce/exacerbate PIH.  Methods: This qualitative review provides an overview of topical treatments for melasma and PIH, including recent data from an investigator-initiated trial of the retinoid tazarotene.  Results: Topical hydroquinone (HQ) in the form of triple combination HQ 4%/tretinoin 0.05%/fluocinolone acetonide 0.01% cream is the gold-standard treatment for melasma and PIH but should not be used long-term due to safety concerns. Efficacy data for OTC/cosmeceutical products are limited or lacking. Topical retinoids are efficacious and safe, though dose and formulation differences may affect tolerability. Tazarotene 0.045% polymeric emulsion lotion demonstrated good efficacy, safety, and tolerability over 24 weeks in adult female patients with moderate-to-severe melasma and/or PIH. CONCLUSIONS: There are multiple topical treatments available for dyspigmentation. However, many are lacking efficacy data and others are limited by tolerability or safety concerns. Retinoids, such as tazarotene, may be an efficacious and safe treatment for melasma or PIH. J Drugs Dermatol. 2023;22(11):1118-1123     doi:10.36849/JDD.7754.

Emerging drugs for the treatment of acne: a review of phase 2 & 3 trials.

INTRODUCTION: Acne vulgaris is one of the commonest dermatoses encountered in a dermatology clinic. Although the inflammatory processes are centered around the pilosebaceous unit, a myriad of external factors that alter the pathogenesis have been hypothesized. Newer therapies are focused on targeting these as possible scaffolds for drug development. Existing topical and oral medications have considerable overlap between pharmacotherapy and cosmeceuticals directed toward acne treatment making new drug development extremely competitive and financially burdening. Teratogenicity associated with retinoids, cutaneous adverse effects of topical anti-acne medications, and lack of long-term remission induction are a few hindrances that have to be tackled by novel therapies. AREAS COVERED: Numerous topical and systemic medications for acne vulgaris are undergoing clinical trials presently. The review has dealt with anti-acne drugs undergoing phase II and III clinical trials with emphasis on the rationale of various combinations in tandem with the complex pathogenesis of the disease. EXPERT OPINION: The current strategies in new drug development target sebocyte function, neo-inflammatory mediators, and methods combatting drug resistance while broadening the anti-microbial spectrum against Cutibacterium acnes. A holistic approach is pivotal to strengthen the management protocol for acne to achieve precision dermatological practice.

Tazarotene 0.045% Lotion: A Novel Retinoid Formulation.

OBJECTIVE: The aim of this study is to review the available data on efficacy and tolerability of tazarotene 0.045% lotion. DATA SOURCES: A literature search of MEDLINE (PubMed) and EMBASE databases was completed in November 2021. STUDY SELECTION AND DATA EXTRACTION: Articles that discussed efficacy, tolerability, and pharmacology of tazarotene 0.045% lotion, written in English and published before mid-November 2021, were assessed. DATA SYNTHESIS: In two, 12-week phase III clinical trials, tazarotene 0.045% lotion had higher rates of treatment success (study 1: 25.5% and study 2: 29.6%) than individuals who received the vehicle (study 1: 13.0% and study 2: 17.3%) (both Ps < 0.001). Participants treated with tazarotene 0.045% lotion had greater least squares mean reduction in inflammatory (study 1: 55.5% and study 2: 59.5%) and noninflammatory (study 1: 51.4% and study 2: 60%) acne lesions when compared with vehicle (inflammatory acne lesions, study 1: 45.7% and study 2:49%; noninflammatory acne lesions, study 1: 41.5% and study 2: 41.6%) (P < 0.001 for studies 1 and 2). Tazarotene 0.045% lotion was well tolerated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Retinoids are first-line therapy in the treatment of acne vulgaris. However, many patients experience cutaneous irritation, which can decrease patient adherence and efficacy. Tazarotene 0.045% lotion is the first retinoid to utilize polymeric emulsion technology (PET) to efficiently distribute the medication across the skin, decreasing adverse effects while maintaining efficacy. CONCLUSIONS: Tazarotene 0.045% lotion is an effective and well-tolerated retinoid recently approved by the US Food and Drug Administration (FDA) for treating acne vulgaris in individuals 9 years of age and older.

A systematic review of oral retinoids for treatment of acneiform eruptions induced by epidermal growth factor receptor inhibitors.

Epidermal growth factor receptor inhibitors (EGFRi) are now standard of care in patients with EGFR mutations in non-small cell lung cancer (NSCLC) and are increasingly being used in other EGFR mutated cancers, including gastrointestinal, and head and neck. However, EGFRi are well known to cause acneiform eruptions, which are shown to positively correlate with tumor response to treatment, but may be severe enough to cause interruption of their treatment. Although most guidelines call for the use of tetracyclines to treat these acneiform eruptions, there is mounting evidence for the use of systemic retinoids instead. The objective of this review is to summarize available data on the use of systemic retinoids for management of acneiform eruptions on EGFRi. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. MEDLINE and EMBASE were searched from database inception until December 10th, 2021. All articles were screened and relevant data extracted independently in duplicate by two reviewers. In total, 16 case reports, case series and retrospective reviews were included. Forty-three patients were treated with retinoids for their acneiform eruption due to EGFRi. The majority (77%) noted moderate to significant improvement after treatment initiation with minimal adverse events (16%). The findings of this systematic review suggest that systemic retinoids are a safe and effective therapy for the management of acneiform eruptions induced by EGFRi.

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.

Advances in Topical Management of Adolescent Facial and Truncal Acne: A Phase 3 Pooled Analysis of Safety and Efficacy of Trifarotene 0.005% Cream.

PURPOSE: Acne vulgaris is very common among adolescents and young adults. It is important for clinicians who provide care to these patients to have a plan of action for assessing and managing acne in daily practice. METHODS: Post-hoc analysis of two large-scale phase 3 pivotal trials of trifarotene 0.005% cream, focusing on efficacy, safety, and tolerability in the subgroup of subjects aged 12 to 17, inclusive. RESULTS: Trifarotene was effective and well tolerated on both the face and trunk in patients ages 12-17 with moderate acne. There was a low and acceptable rate of adverse events and tolerability was favorable. CONCLUSIONS: Trifarotene monotherapy was associated with good clinical efficacy, safety, and tolerability. Once-daily application offers convenience for patients, and the low concentration of trifarotene makes it well-suited to use on large skin areas such as the trunk. J Drugs Dermatol. 2022;21(6):582-586. doi:10.36849/JDD.6778.

Trifarotene for the Treatment of Facial and Truncal Acne.

OBJECTIVE: This article reviews clinical trials to assess the efficacy, safety, and clinical application of trifarotene 0.005% cream (Aklief). DATA SOURCES: A systematic review of the literature was performed using the terms trifarotene OR Aklief OR CD5789 in MEDLINE (PubMed) and EMBASE databases. Articles prior to May 2020 were considered for inclusion. Bibliographies and ClinicalTrials.gov were also searched to identify further studies. STUDY SELECTION AND DATA EXTRACTION: Relevant English language and human studies related to pharmacology, clinical trials, and safety were considered. DATA SYNTHESIS: In the 52-week phase III trial, treatment success rates for facial acne (Investigator Global Assessment [IGA] rating of no or almost no acne) and truncal acne (Physician's Global Assessment [PGA] rating of no or almost no acne) were 65.1% and 66.9%, respectively. Overall success rates (IGA and PGA success in the same patient) were 57.9%; 52.8% of patients had a Dermatology Quality of Life Index score of 0 or 1, compared with 22.6% at baseline. Trifarotene was well tolerated, with pruritus, irritation, and sunburn as the most common adverse effects. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Trifarotene is a newly Food and Drug Administration-labeled fourth-generation topical retinoid that shows particular promise in the treatment of facial and truncal acne vulgaris. It is an effective and safe addition to currently available retinoids. CONCLUSION: Trifarotene is effective and safe for treatment of facial and truncal acne. Future trials should compare its efficacy and tolerability with that of the older, clinically established retinoids. Despite efficacy, cost may be a prohibitive factor.

Topical and systemic retinoids for the treatment of cutaneous viral warts: A systematic review and meta-analysis.

Cutaneous viral warts (CVW), caused by human papillomavirus, often have a self-limited course. However, some patients experience a recalcitrant disease despite treatment. Retinoids are considered the mainstay of therapy in many dermatologic diseases. Data on their use for viral warts are limited. To systematically review the published evidence on the efficacy and safety of retinoids for the treatment of CVW. A systematic review and meta-analysis of topical or systemic retinoid treatment for CVW was performed in accordance with the PRISMA statement. The primary outcome was clinical response; secondary outcomes were recurrence rate and adverse events. Fourteen publications including 399 patients treated exclusively with retinoids (65% topical, 35% systemic) were evaluated. The complete response rate was 64% (95% CI, 46-78%; I2 =80%) for topical treatment and 61% (95% CI, 44-76%; I2 =69%) for systemic treatment. The most common side effects were irritant contact dermatitis and cheilitis, respectively. Relapse rates were 6% and 17%, respectively. The reviewed studies were considerably heterogenous and most lacked a control group. Both topical and systemic retinoids are effective and safe as monotherapy for CVW. Further studies are required to determine their exact role in this setting.

Long-term safety and efficacy of trifarotene 50 µg/g cream, a first-in-class RAR-γ selective topical retinoid, in patients with moderate facial and truncal acne.

BACKGROUND: Treatment for both facial and truncal acne has not sufficiently been studied. OBJECTIVES: To evaluate the long-term safety and efficacy of trifarotene in both facial and truncal acne. METHODS: In a multicentre, open-label, 52-week study, patients with moderate facial and truncal acne received trifarotene 50 µg/g cream (trifarotene). Assessments included local tolerability, safety, investigator and physician's global assessments (IGA, PGA) and quality of life (QOL). A validated QOL questionnaire was completed by the patient at Baseline, Week 12, 26 and 52/ET. RESULTS: Of 453 patients enrolled, 342 (75.5%) completed the study. Trifarotene-related treatment-emergent adverse events (TEAEs) were reported in 12.6% of patients, and none was serious. Most related TEAEs were cutaneous and occurred during the first 3 months. Signs and symptoms of local tolerability were mostly mild or moderate and severe signs, and symptoms were reported for 2.2% to 7.1% of patients for the face and 2.5% to 5.4% for the trunk. Local irritation increased during the first week of treatment on the face and up to Weeks 2 to 4 on the trunk with both decreasing thereafter. At Week 12, IGA and PGA success rates were 26.6% and 38.6%, respectively. Success rates increased to 65.1% and 66.9%, respectively at Week 52. Overall success (both IGA and PGA success in the same patient) was 57.9% at Week 52. At Week 52 visit, 92/171 (53.8%) patients who had completed their assessments had scores from 0 to 1 (i.e. no effect of acne on their QOL) vs. 47/208 (22.6%) patients at Baseline visit. CONCLUSION: In this 52-week study, trifarotene was safe, well tolerated and effective in moderate facial and truncal acne.

A Novel Topical Retinoid for Acne: Trifarotene 50 µg/g Cream

Trifarotene 50 µg/g cream is a fourth generation topical retinoid with retinoic acid receptor gamma selectivity. It was recently approved by the US FDA and Health Canada for the topical treatment of facial and truncal acne for those aged 9 and older based on two identically designed phase 3 trials demonstrating superiority in lesion count reduction and global acne improvement compared to vehicle. These studies and a 1 year study also demonstrated safety and tolerability with cutaneous adverse events developing in an anticipated timeframe (1 week) for the face. These were of lesser degree and tended to develop later at the trunk. Future studies will be required to evaluate the comparative efficacy of trifarotene 50 µg/g cream against other treatments for acne.

Suppressive Effect of Arctium Lappa L. Leaves on Retinal Damage Against A2E-Induced ARPE-19 Cells and Mice.

Age-related macular degeneration (AMD) is a major cause of irreversible loss of vision with 80-90% of patients demonstrating dry type AMD. Dry AMD could possibly be prevented by polyphenol-rich medicinal foods by the inhibition of N-retinylidene-N-retinylethanolamine (A2E)-induced oxidative stress and cell damage. Arctium lappa L. (AL) leaves are medicinal and have antioxidant activity. The purpose of this study was to elucidate the protective effects of the extract of AL leaves (ALE) on dry AMD models, including in vitro A2E-induced damage in ARPE-19 cells, a human retinal pigment epithelial cell line, and in vivo light-induced retinal damage in BALB/c mice. According to the total phenolic contents (TPCs), total flavonoid contents (TFCs) and antioxidant activities, ALE was rich in polyphenols and had antioxidant efficacies on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and 2',7'-dichlorofluorescin diacetate (DCFDA) assays. The effects of ALE on A2E accumulation and A2E-induced cell death were also monitored. Despite continued exposure to A2E (10 µM), ALE attenuated A2E accumulation in APRE-19 cells with levels similar to lutein. A2E-induced cell death at high concentration (25 µM) was also suppressed by ALE by inhibiting the apoptotic signaling pathway. Furthermore, ALE could protect the outer nuclear layer (ONL) in the retina from light-induced AMD in BALB/c mice. In conclusion, ALE could be considered a potentially valuable medicinal food for dry AMD.

Randomized phase 3 evaluation of trifarotene 50 µg/g cream treatment of moderate facial and truncal acne.

BACKGROUND: Acne vulgaris often affects the face, shoulders, chest, and back, but treatment of nonfacial acne has not been rigorously studied. OBJECTIVES: Assess the safety and efficacy of trifarotene 50 µg/g cream, a novel topical retinoid, in moderate facial and truncal acne. METHODS: Two phase III double-blind, randomized, vehicle-controlled, 12-week studies of once-daily trifarotene cream versus vehicle in subjects aged 9 years or older. The primary end points were rate of success on the face, as determined by the Investigator's Global Assessment (clear or almost clear and ≥2-grade improvement), and absolute change from baseline in inflammatory and noninflammatory counts from baseline to week 12. The secondary end points were rate of success on the trunk (clear or almost clear and ≥2-grade improvement) and absolute change in truncal inflammatory and noninflammatory counts from baseline to week 12. Safety was assessed through adverse events, local tolerability, vital signs, and routine laboratory testing results. RESULTS: In both studies, at week 12 the facial success rates according to the Investigator's Global Assessment and truncal Physician's Global Assessment and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P < .001) in favor of trifarotene when compared with the vehicle. LIMITATIONS: Adjunctive topical or systemic treatments were not studied. CONCLUSION: These studies demonstrate that trifarotene appears to be safe, effective, and well tolerated in treatment of both facial and truncal acne.

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.

Topical Vehicle Formulations in the Treatment of Acne.

Topical treatment is the mainstay of acne therapy. The most commonly prescribed topical medications for acne include benzoyl peroxide, clindamycin, and retinoids. Despite their effectiveness in treating mild to moderate acne vulgaris, these topical medications are found to be irritating, and are historically associated with poor tolerability and diminished patient adherence. Thus, choosing the right formulation that will be effective and well tolerated is essential. Novel formulations that optimize drug concentration and utilize improved delivery vehicles have helped to enhance the tolerability and efficacy, and allow for less frequent application or co-application of drugs that were previously considered incompatible. This article will review the goals of topical therapy for the treatment of acne, in addition to common therapies and their challenges. Advanced formulations and combination formulations of benzoyl peroxide, clindamycin, and tretinoin will also be discussed. J Drugs Dermatol. 2018;17(6 Suppl):s6-10.

Synthesis and activity of the salicylic acid ester of bakuchiol in psoriasis-surrogate keratinocytes and skin substitutes.

BACKGROUND: Topical retinoids are effective in retarding skin ageing and restoring homeostasis in skin conditions such as psoriasis. However their adverse effects (AEs), which include irritation (retinoid dermatitis), photosensitivity and teratogenicity, limit their use and patient compliance. Development of retinoid analogues with minimal AEs would allow a broader and more compliant use. AIM: To synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a modulatory gene expression profile similar to retinoids, using as reference three prescription retinoids: tretinoin, tazarotene and adapalene. METHODS: We hypothesized that because bakuchiol salicylate has a structure entirely different from existing retinoids, there would be at least a partial uncoupling of AEs from the skin-normalizing activity of this retinoid. This hypothesis was tested at the transcriptional level in psoriatic cytokine-treated cultures of keratinocytes and organotypic skin substitutes, using DNA microarrays and custom PCR arrays. RESULTS: Evaluation of the gene expression profile of bakuchiol salicylate revealed elimination of several components of the retinoid-like proinflammatory response and teratogenic signature, without a substantial loss of normalizing potential. A possible mechanism of action, consisting of keratinocyte desensitization to psoriatic cytokine signalling through inhibition of the signal transducer and regulator of transcription (STAT)1/3/interferon inflammatory signal transduction axis was also identified. CONCLUSION: Bipartite materials obtained by merging two skin-active entities with specific, complementary bioactivities, such as bakuchiol and salicylic acid, may yield a new class of functional retinoids.