Topical Therapy for Atopic Dermatitis: What is New and the New Paradigm.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder that requires a complex management strategy, which often involves multiple and diverse topicals and systemic treatment regimens. While topical steroids and more recently calcineurin inhibitors have been the mainstay therapy for mild-to-moderate disease, recent advances in the understanding of AD pathogenesis have led to the development of different new targets, rapidly widening our therapeutic armamentarium. This review summarizes their efficacy and safety data. We also review topical optimization strategies, including the recently published topical volume calculator, to maximize long-term disease control, especially when using multiple agents at the same time.

Effect of Topical Microencapsulated Benzoyl Peroxide on the Skin Microbiome in Rosacea: A Randomized, Double-Blind, Crossover, Vehicle-Controlled Clinical Trial.

Objective: We sought to evaluate changes in microbiome biodiversity and physical properties of the skin after eight weeks of once-daily topical microencapsulated benzoyl peroxide (E-BPO) compared to vehicle cream in participants with rosacea. Methods: This was a randomized, double-blind, crossover, single-center, vehicle-controlled evaluation of E-BPO on the skin microbiome in rosacea. Participants had facial rosacea with global severity of 3 or 4 on the Investigator Global Assessment (IGA) scale. In the Treatment 1-2 group, participants received E-BPO for eight weeks then switched to vehicle cream for four weeks. In the Treatment 2-1 group, participants received vehicle cream for eight weeks, then E-BPO for four weeks. Results: Thirty-one participants were enrolled and randomly assigned to either group. Demographic characteristics were comparable between the treatment groups. After eight weeks of E-BPO treatment, there was a marked reduction in the relative abundance of Staphylococcus accompanied by an increase in Cutibacterium. At the species level, there was an increase in the relative abundance of C. acnes and a decrease in abundance of S. epidermidis. No noticeable difference was detected at the genus or species level at Week 8 in the 2-1 group. Sebum level, IGA, lesion counts, facial erythema, and inflammatory scores were improved with E-BPO versus vehicle cream. Adverse events were mild or moderate in severity. Limitations: The study included a small number of subjects and only surface-swabs were used for microbiome sampling. Conclusion: E-BPO shifted the skin microbiome in rosacea and demonstrated improvements in clinical symptoms and skin physical properties and a well-tolerated safety profile. US National Library of Medicine; Trial ID: NCT05675501]; URL: clinicaltrials.gov.

Current and emerging drugs for the treatment of pruritus: an update of the literature.

INTRODUCTION: Pruritus, particularly in its chronic form, often imposes significant suffering and reductions in patients' quality of life. The pathophysiology of itch is varied depending on disease context, creating opportunities for unique drug development and multimodal therapy. AREAS COVERED: The purpose of this article is to provide an update of the literature regarding current and emerging therapeutics in itch. We review the multitudes of drug targets available and corresponding drugs that have shown efficacy in clinical trials, with a particular emphasis on phase 2 and 3 trials and beyond. Broadly, these targets include therapies directed against type 2 inflammation (i.e. Th2 cytokines, JAK/STAT, lipid mediators, T-cell mediators, and other enzymes and receptors) and neural receptors and targets (i.e. PARs, TRP channels, opioid receptors, MRGPRs, GABA receptors, and cannabinoid receptors). EXPERT OPINION: Therapeutics for itch are emerging at a remarkable pace, and we are entering an era with more and more specialized therapies. Increasingly, these treatments are able to relieve itch beyond their effect on inflammation by directly targeting the neurosensory system.

Systematic review of randomized controlled trials of topicals for actinic keratosis field therapy.

Cutaneous field cancerization in dermatology describes the anatomic region of photodamaged skin with actinic keratoses (AKs) or cutaneous squamous cell carcinoma (cSCC) that is surrounded by cellular atypia, forming a dysplastic field. The concept of field cancerization is especially relevant in dermatology, as actinic keratoses and the surrounding dysplastic region can progress to carcinomas, necessitating the treatment of the field. Recent research has focused on field-directed therapy using topical agents. This study aims to systematically review randomized controlled trials on topical treatments for actinic keratosis field cancerization, following the PRISMA guidelines. Clinical recommendations were based on the Oxford Centre for Evidence-Based Medicine. We identified 20 original randomized controlled trials for topical cutaneous field therapy. 0.5% 5-Fluorouracil/salicylic acid and 0.5% 5-fluorouracil received a clinical recommendation grade of A, while diclofenac sodium received a clinical recommendation grade of B. Calcipotriol/5-fluorouracil, Imiquimod, sunscreen combination therapies, and tirbanibulin received a recommendation grade of C. This review provides a framework for clinicians when considering topical treatments for patients with field cancerization.

Calcipotriol and Betamethasone Dipropionate Cream Based on PAD Technology for the Treatment of Plaque Psoriasis: A Narrative Review.

Topical treatment plays a crucial role in psoriasis management, with non-adherence being a major barrier to treatment success. The fixed-dose combination of calcipotriol (CAL) and betamethasone dipropionate (BDP) represents the first-line choice in topical psoriasis treatment. A CAL/BDP cream based on polyaphron dispersion (PAD) Technology has emerged as a novel formulation for a more convenient topical treatment of psoriasis. This article aims to summarize the most relevant published evidence about CAL/BDP PAD-cream and its underlying PAD Technology. The PAD Technology enables CAL and BDP stability in an aqueous cream through a multimolecular shell structure, as well as it increases the penetration of both active ingredients into the epidermis and dermis. This technology also demonstrated to increase the cosmetic acceptability and to provide the desirable sensory properties for a topical psoriasis treatment. Two phase III clinical trials have been conducted so far with CAL/BDP PAD-cream. Findings from both trials revealed high efficacy with a fast onset of action, a favourable safety and tolerability profile and convenience for CAL/BDP PAD-cream compared to CAL/BDP gel. In the trial including patients with psoriasis affecting the scalp (MC2-01-C7), results support the use of CAL/BDP PAD-cream in scalp psoriasis. An anchored matching-adjusted indirect comparison (MAIC) was conducted to compare CAL/BDP PAD-cream and CAL/BDP foam, as both products had been previously compared to CAL/BDP gel. CAL/BDP PAD-cream and CAL/BDP foam showed equivalent efficacy and quality of life at their recommended treatment duration, whereas greater treatment satisfaction for CAL/BDP PAD-cream was found after one week of treatment. Overall, the high patient acceptability and treatment satisfaction observed with CAL/BDP PAD-cream in clinical trials may lead to improved adherence and hence higher efficacy in clinical practice.

Long-term Efficacy and Safety of Microencapsulated Benzoyl Peroxide Cream, 5%, in Rosacea: Results From an Extension of Two Phase III, Vehicle-controlled Trials.

Objective: We sought to assess the long-term safety and tolerability of microencapsulated benzoyl peroxide cream, 5% (E-BPO cream, 5%), in subjects with rosacea. Efficacy and tolerability have been previously demonstrated in two 12-week, randomized, double-blind, vehicle-controlled Phase III trials. Methods: In this open-label extension study (NCT03564145; clinicaltrials.gov), all subjects from the initial placebo-controlled Phase III trials could receive E-BPO cream, 5%, for up to an additional 40 weeks, up to a total of 52 weeks of E-BPO cream, 5%, exposure. If a subject was assessed at study visits as "clear" or "almost clear" using the 5-point Investigator Global Assessment (IGA) scale (IGA 0 or 1), E-BPO cream, 5%, was not dispensed. If a subject was assessed as "mild to severe" (IGA 2+), E-BPO cream, 5%, was applied daily until they reached "clear" or "almost clear." Results: The safety and tolerability profile for E-BPO cream, 5%, was similar to that reported in the Phase III studies. Five subjects (0.9%) discontinued study drug due to treatment-related adverse events, and 17 subjects (3.2%) experienced an adverse event considered related to study drug. IGA success after 40 weeks of active treatment was 66.5 percent for subjects continuing from the Phase III vehicle group (n=172) and 67.6 percent for subjects who continued Phase III E-BPO cream, 5% (n=363). The study ended early in accordance with the protocol. Limitations: Safety and tolerability of E-BPO were not compared with those of unencapsulated BPO. Conclusion: E-BPO cream, 5%, showed a favorable safety and tolerability profile during this 40-week, open-label extension study.

Update on Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a lifetime prevalence of up to 20% which can occur at any age but is most common among children. There is a significant burden of pediatric AD in the primary care setting; thus, the ability to recognize and manage AD is of utmost importance to pediatricians. Treatment of AD requires a multifaceted approach based on a patient's severity including behavioral modifications, topical and systemic pharmacologic therapies, and phototherapy.

Impact of Topical Vehicles and Cutaneous Delivery Technologies on Patient Adherence and Treatment Outcomes in Acne and Rosacea.

Objective: Topical therapies remain the mainstay in treating patients with acne and rosacea. However, emerging real-world evidence demonstrates that desired treatment outcomes might not be achieved if patient satisfaction and adherence are low. Poor tolerability of active drug(s) and vehicle components and/or the drug delivery system could negatively influence adherence. Additionally, adherence might be lower with complex treatment regimens involving the application of multiple topical formulations. Optimizing vehicle tolerability and simplifying regimens that use fixed-dose combinations may improve treatment outcomes, better patient satisfaction, and reduce overall treatment costs. This qualitative review discusses several innovative drug delivery technologies and formulations aimed at improving patient satisfaction and adherence. Methods: The authors conducted a search of current and emerging topical drug delivery technologies used in clinical studies, reviewed primary literature on the chemical characteristics of topical dosage forms, and compared the impacts on treatment outcomes for acne and rosacea. Results: This article provides insight into innovative vehicles and drug delivery systems that have emerged allowing for fixed-dose combinations of incompatible active drugs and improving the tolerability of historically irritative active ingredients. Limitations: Further research is needed to fully highlight the impact of patient satisfaction and modern topical formulations on adherence and treatment outcomes. Conclusion: Drug microencapsulation is a delivery technology that has enabled development of a topical fixed-dose combination of benzoyl peroxide and tretinoin preventing the oxidation of tretinoin by benzoyl peroxide and improving the tolerability of the active ingredients.

Guidelines of care for the management of atopic dermatitis in adults with topical therapies.

BACKGROUND: New evidence has emerged since the 2014 guidelines that further informs the management of atopic dermatitis (AD) with topical therapies. These guidelines update the 2014 recommendations for management of AD with topical therapies. OBJECTIVE: To provide evidence-based recommendations related to management of AD in adults using topical treatments. METHODS: A multidisciplinary workgroup conducted a systematic review and applied the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach for assessing the certainty of evidence and formulating and grading recommendations. RESULTS: The workgroup developed 12 recommendations on the management of AD in adults with topical therapies, including nonprescription agents and prescription topical corticosteroids (TCS), calcineurin inhibitors (TCIs), Janus kinase (JAK) inhibitors, phosphodiesterase-4 inhibitors (PDE-4), antimicrobials, and antihistamines. LIMITATIONS: The pragmatic decision to limit the literature review to English-language randomized trials may have excluded data published in other languages and relevant long-term follow-up data. CONCLUSIONS: Strong recommendations are made for the use of moisturizers, TCIs, TCS, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.

Executive summary: American Academy of Dermatology guidelines of care for the management of atopic dermatitis in adults with topical therapies.

These guidelines update the 2014 recommendations for management of atopic dermatitis in adults with topical therapies. A multidisciplinary workgroup employed best practices for guideline development, including a systematic review of the evidence and application of the Grading of Recommendations, Assessment, Development, and Evaluation approach for assessing the certainty of the evidence and formulating and grading recommendations. The evidence on atopic dermatitis treatment supported strong recommendations for the use of nonprescription moisturizers, topical calcineurin inhibitors, topical corticosteroids, and topical PDE-4 and JAK inhibitors. Conditional recommendations are made for the use of bathing and wet wrap therapy and against the use of topical antimicrobials, antiseptics, and antihistamines.

Current and Emerging Therapies in Pediatric Atopic Dermatitis.

Atopic dermatitis (AD) is the most common inflammatory skin disease seen in children. It is a heterogeneous disorder, with a variety of associated manifestations and symptoms. Cases may range from mild to severe. As a result, a spectrum of prescription and nonprescription therapies may be utilized when managing this condition. This article provides an extensive overview of these therapies, with equal consideration provided to current, emerging, and alternative options used in the pediatric population.

An anchored matching-adjusted indirect comparison of fixed-dose combination calcipotriol and betamethasone dipropionate (Cal/BDP) cream versus Cal/BDP foam for the treatment of psoriasis.

OBJECTIVES: To undertake a comparison of Cal/BDP cream versus foam for the treatment of plaque psoriasis, with cross-trial population differences accounted for. MATERIALS AND METHODS: An anchored matching-adjusted indirect comparison was undertaken, using individual patient data for Cal/BDP cream and published aggregated data for Cal/BDP foam. Altogether, 11 outcomes were analyzed, including PGA success, mPASI75, DLQI-related outcomes and treatment satisfaction across numerous domains. For each outcome an odds ratio or mean difference was calculated to represent the relative efficacy of Cal/BDP cream versus foam. Methods were guided by NICE Decision Support Unit recommendations. RESULTS: After adjustment, baseline characteristics were balanced across treatment arms in each analysis. There were no statistically significant differences in PGA success, mPASI75 or DLQI outcomes between Cal/BDP cream and foam when they were compared after their recommended treatment durations (8 weeks for cream and 4 weeks for foam). For treatment satisfaction after 1 week of treatment, Cal/BDP cream was significantly superior to the Cal/BDP foam in all but one domain of the questionnaire. CONCLUSIONS: Cal/BDP cream and Cal/BDP foam have equivalent efficacy and HRQoL (measured in DLQI) outcomes when used for the topical treatment of plaque psoriasis at their recommended treatment durations. A comparison of treatment satisfaction assessments after 1 week of treatment demonstrated that patients find Cal/BDP cream to be more convenient than foam.

An insight on topically applied formulations for management of various skin disorders.

Various types of skin disorders across each age group and in each part of geographical world are very dreadful. Despite not being fatal each time they are always of social and mental concern for suffering individuals, causing complications in millions of patients every day and require comparatively longer duration of treatment. Off late, various topical/transdermal formulations have been widely explored for the treatment of various skin ailments. The efficiency of topical therapy depends on various physiochemical properties of drugs like particle size, particle size distribution, partition coefficient, viscosity of dosage form, skin permeability, skin condition and the site of application. Therefore, in plenty of examples, long-acting topical formulations have shown to be markedly excellent in comparison to conventional dosage forms. The major advantages of topical formulations accrue from their demonstrated ability: (i) Reduced serious side effects that may occur due to undesirably higher systemic absorption of drug. (ii) Enhancement of drug accumulation at the desired site. (iii) Easy incorporation of enormous range of hydrophilic and hydrophobic drugs and (iv) Reduced risk of dose dumping and comparatively easy termination of drug release. The prospective applications of topically applied formulations and the deposition of pharmaceuticals into the skin are examined.

Enhancing Topical Pharmacotherapy for Acne and Rosacea: Vehicle Choices and Outcomes.

The choice of vehicle is an important consideration in the treatment of acne and rosacea. Agents used to treat these common conditions may be limited by multiple factors, including poor stability during storage, limited residence time in the skin and follicular unit, and high potential for skin irritation. Novel drug delivery systems have been developed to address these problems, including microencapsulation, liposomal encapsulation, and the use of a variety of nanocarriers. New vehicle technologies for acne and rosacea treatments have appeared over the past 20 years and have somewhat improved stability, tolerability, and possibly efficacy. One of the latest vehicle technologies in acne and rosacea to enhance efficacy, stability, and tolerability is microencapsulation of benzoyl peroxide and tretinoin, which resulted in significant efficacy and good tolerability in patients with each of these two diseases. Other new vehicle technologies include a polymeric form of tretinoin and a microsphere product that combines tretinoin plus clindamycin. It is likely that there will be more reports of clinical success as experience with the rapidly evolving delivery technologies increases. This review summarizes drug delivery systems that have been developed with the aim of improving outcomes for patients being treated for either acne or rosacea. It also focuses, where possible, on formulations that have been evaluated in clinical studies.

Topical Treatments for Melasma and Their Mechanism of Action.

Objective: We conducted a review of topical agents currently used in melasma, discussing their mechanism of action, efficacy, safety, and tolerability, with an update on newer treatments. Methods: A systematic review from PubMed database was performed, using PRISMA guidelines. The search was limited to English and Spanish studies that were double or single blinded, prospective, controlled or randomized clinical trials, reviews of literature, and meta-analysis studies. Results: 348 studies were analyzed; 80 papers met inclusion criteria. Triple combination (TC) therapy and hydroquinone (HQ) are still the most well-studied agents with strong evidence-based recommendation. TC therapy remains the gold standard of care based on efficacy and patient tolerability. Evidence has shown ascorbic acid, azelaic acid, glycolic acid, kojic acid, salicylic acid, and niacinamide to be effective as adjuvant therapies with minimal side effects. Tranexamic acid (TA) and cysteamine have become recent agents of interest due to their good tolerability, however more trials and studies are warranted. Less evidence exists for other topical agents, such as linoleic acid, mulberry extract oil, rucinol, 2% undecylenoyl phenylalanine, and epidermal growth factors agents. Limitations: Some studies discussed represented a low sample size, and there is an overall lack of recent studies with larger populations and long-term follow up. Conclusions: TC therapy continues to be the gold standard of care. Topical cysteamine and TA are newer options that can be incorporated as adjuvant and maintenance treatments into a patient's regimen. Cysteamine and topical TA have no known severe adverse effects. Evidence comparing other topical adjuvant treatments to HQ, maintains HQ as the gold standard of care.

An improved method for the determination of cannabidiol in topical products using ultrasound-assisted extraction and gas chromatography-mass spectrometry.

The recent surge in the sale of cannabidiol (CBD)-based topicals has risen rapidly in recent years, as it can be used to treat a multitude of skin disorders. However, there is minimal regulation concerning actual CBD content in these products. Topicals on the market may contain various concentrations of CBD and may be combined with a range of other compounds. The concentration of CBD has to be determined before the products enter the market. For this reason, a selective analytical method was developed using a 23 factorial design; and validated to determine CBD content in various topicals based on ultrasound-assisted extraction (UAE) followed by gas chromatography coupled to mass spectrometry (GC-MS). The method showed good precision (relative standard deviation ≤ 7.7%), accuracy at three concentration levels (recovery > 97.9%) for three different matrices, acceptable linearity (R2 > 0.99), and limit of detection (0.05 µg/mg). The method was successfully applied to the analysis of five commercial topicals. The proposed method is rapid, sensitive, precise, and accurate. In addition, it does not require derivatization and it is suitable for the determination of CBD in topicals for quality control purposes.

Topical and Conventional Systemic Treatments in Atopic Dermatitis: Have They Gone Out of Fashion?

Atopic dermatitis is a Th2 disease, due to relapse of IL-4 and IL-13 by Th2 cells. Despite the approval by FDA of dupilumab, the first monoclonal antibody for the severe forms, traditional drugs remain a milestone for the treatment of this dermatosis. Dermatologists need a good knowledge of all therapies for an integrated and personalized management of patients.

Emerging topical therapies to treat pigmentary disorders: an evidence-based approach.

BACKGROUND: Hyperpigmentation disorders are commonly encountered in dermatology clinics. The use of prescription-grade and over-the-counter topical lightening agents has increased in popularity, leading to a substantial growth of research over the past decade. OBJECTIVE: We seek to review clinical studies evaluating the use of different Rx-grade and OTC ingredients in treating hyperpigmentation. METHODS AND MATERIALS: A comprehensive search on PubMed was conducted to identify patient-based evidence on the most common ingredients used as topical lightening agents: arbutin, ascorbic acid, cysteamine, hydroquinone, kojic acid, niacinamide, retinoids, and triple-combination therapy. The topicals were classified as either prescription-grade or over-the-counter. RESULTS: Varying levels of evidence support the use of topicals in treating hyperpigmentation. There were more clinical trials examining Rx-grade products than OTC products. Mild but tolerated side effects are noted in many of these agents. CONCLUSION: Careful monitoring and adjustment of doses will be needed to maximize skin lightening benefits and minimize side effects.