Comparison of psoriasis guidelines for use of apremilast in the United States and Europe: a critical appraisal and comprehensive review.

PURPOSE: This review article serves to compare global dermatologic organizations and the available clinical practice guidelines for the use of apremilast in the treatment of psoriasis. MATERIALS AND METHODS: Guidelines from the American Academy of Dermatology (AAD), the National Psoriasis Foundation (NPF), the European S3, the National Institute for Health and Care Excellence (NICE), the French Society of Dermatology (SFD), the Swiss S1, and Italy were reviewed and compared. RESULTS: Of the American and European guidelines available for use of apremilast, several organizations are in agreement regarding the dosage of apremilast, but there are significant disagreements concerning matters such as medication indication, pretreatment laboratory testing, and contraindications to therapy. CONCLUSION: Apremilast is an effective and well-tolerated treatment option for patients with psoriasis and should be considered in the line of therapy that dermatologists discuss with their patients, especially those with contraindications to other systemic therapies such as biologics. Consideration should be given to the evidence-based recommendations of global dermatology organizations to help guide therapeutic decisions.

Controversial cardiovascular and hematologic comorbidities in atopic dermatitis.

Atopic dermatitis' (AD) systemic involvement is wide-reaching. The cardiovascular and hematological comorbidities of AD have potential for considerable economic and physical burden; however, data surrounding the association between these comorbidities and AD is controversial. This review discusses the cardiovascular and hematological comorbidities of AD, detailing the conflicting evidence, pathophysiology, and connection to medications. A PubMed search was conducted for studies detailing the association of cardiovascular and hematological comorbidities with AD, providing approximately 30 results. Additional searches were conducted for studies discussing the pathophysiology of these comorbidities and possible connections to AD medications. Various studies highlight either positive, negative, or no association of AD with hypertension, stroke, myocardial infarction, heart failure, and thrombosis. Coronary heart disease, angina, peripheral artery disease, and anemia are consistently positively associated with AD. However, the attributable risks of AD for stroke, myocardial infarction, heart failure, and atrial fibrillation are low (25 per 100,000 persons [99% CI 6-44], 12 per 100,000 persons [99% CI  - 4-27], 40 per 100,000 persons [99% CI 22-57], and 37 per 100,000 persons [99% CI 15-55]), respectively. The pathophysiology underlying these potential associations is not entirely clear. Corticosteroids, cyclosporine, and antimetabolites, all used to treat AD, may also be associated with many of these comorbidities. AD's controversial associations with cardiovascular and hematological diseases complicates management as it is difficult to define recommendations for screening of these comorbidities. A better understanding may help lessen the economic and physical burden of these comorbidities in AD patients.

PrabotulinumtoxinA-xvfs for the Treatment of Moderate-to-Severe Glabellar Lines.

OBJECTIVE: PrabotulinumtoxinA-xvfs (Jeuveau), a botulinum toxin type A, was approved by the Food and Drug Administration for the temporary improvement in the appearance of moderate-to-severe glabellar lines in February 2019. This article will review phase II and III clinical trials to assess the efficacy, safety, and clinical application of this novel, aesthetic-only drug. DATA SOURCES: A systematic literature review was performed using the terms "glabellar lines AND prabotulinumtoxinA" in the PubMed database. ClinicalTrials.gov was searched to identify nonpublished studies. STUDY SELECTION AND DATA EXTRACTION: Articles written in English between November 2019 and June 2020 discussing phase II and phase III clinical trials were evaluated. DATA SYNTHESIS: By the primary efficacy end point on day 30, more patients achieved a greater than 2-point improvement on the Glabellar Line Scale (GLS) at maximum frown compared with baseline on day 0. The proportions of participants who responded to treatment with prabotulinumtoxinA were 67.5% and 70.4% versus 1.2% and 1.3% in placebo groups across 2 identical clinical trials (P < 0.001). Patients receiving prabotulinumtoxinA experienced greater improvement in GLS at maximum frown on day 30 (87.2%) compared with onabotulinumtoxinA (82.8%) and placebo (4.2%; P < 0.001). PrabotulinumtoxinA was well tolerated across all studies. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review provides a detailed analysis of the safety and efficacy of prabotulinumtoxinA-xvfs and includes special considerations to help guide patients and clinicians. CONCLUSION: PrabotulinumtoxinA is a safe and effective new addition to the repository of available treatments for the appearance of glabellar lines.

A review of secukinumab in psoriasis treatment.

Psoriasis is a systemic immunologic disorder associated with decreased quality of life and numerous co-morbidities, including psoriatic arthritis and cardiovascular disease. Secukinumab, a fully human IgG1 monoclonal antibody, selectively binds IL-17A and is approved by the US FDA and European Medicines Agency for moderate-to-severe plaque psoriasis and psoriatic arthritis. This review examines the efficacy and safety of secukinumab for the treatment of psoriasis using the literature retrieved from the PubMed database. In clinical trials, treatment with secukinumab led to rapid and sustained improvement in Psoriasis Area and Severity Index (PASI) scores, with PASI 90 response rates up to 68.5% at 5 years. Long-term clinical trial and real-world data have established secukinumab as a safe and effective treatment for psoriasis.

Immunogenicity of Biologic and Biosimilar Therapies for Psoriasis and Impact of Novel Immunoassays for Immunogenicity Detection.

Anti-drug antibodies (ADAs) may develop against originator biologic and biosimilar therapies used for the treatment of psoriasis and may be the cause of initial therapeutic non-response or diminished therapeutic response over time. Comparing immunogenicity between therapeutic agents is challenging owing to the variation in assays used for detection, among other reasons. Using the results of a PubMed search for psoriasis clinical trials disclosing the rates of ADAs for originator biologic and biosimilar therapies approved for the treatment of psoriasis within the last 5 years, this review discusses the rates and potential clinical impact of ADA formation in patients with psoriasis managed with originator biologic and biosimilar therapies, along with novel methods of ADA testing. Anti-drug antibodies are detectable in all biologic and biosimilar therapies approved for the treatment of psoriasis in the last 5 years, and the effect of ADAs on clinical response varies by agent. Novel immunoassays used for the detection of ADAs may have increased sensitivity compared with traditional assays, although the increased rate of detection may not correlate with decreased clinical response and the decision to test for the presence of ADAs may vary from patient to patient. Though ADA formation seems ubiquitous with the use of biologic agents for the treatment of psoriasis, the increased rates of ADAs detected by novel immunoassays may not necessarily correlate with decreased treatment efficacy.

Emerging Role of Janus Kinase Inhibitors for the Treatment of Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) is a common chronic, inflammatory skin condition. The pathogenesis of AD involves many cytokines that utilize the Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling cascade; therefore, JAK inhibitors may be used in the treatment of AD. This review aims to evaluate the pathophysiology, efficacy, and safety of JAK inhibitors and their emerging role as a therapeutic option for patients with AD. METHODS: A PubMed search of Phase I, II, and III clinical trials was conducted for relevant literature published between January 2015 and June 2020 utilizing the key terms: JAK inhibitors, atopic dermatitis, efficacy, safety, and treatment. The search was subsequently expanded to include additional terms. RESULTS: In multiple Phase II and III clinical trials, JAK inhibitors were more efficacious than placebo or vehicle controls and slightly more efficacious in direct comparisons to corticosteroids. Overall, JAK inhibitors have a moderate safety profile for use in AD. Some of the more severe theoretical adverse events included thrombosis and reactivation of viral infections. While data remain limited for the long-term efficacy and safety of JAK inhibitor use in patients with AD, many ongoing clinical trials have promising preliminary results. DISCUSSION: Short-term data suggest that both topical and oral JAK inhibitors are efficacious and safe for use in patients with AD, although cases of thrombosis and viral disease have been reported. While the current standard treatments for AD are likely preferred, failed therapy with these agents or corticosteroid phobia may be indications for the use of JAK inhibitors in patients with AD.

Utilization of an Online Cash-Pay Pharmacy for Topical 5-Fluorouracil Prescriptions in Older Patients.

BACKGROUND: High cost of prescription medications presents a challenging issue for older patients with multimorbidities. Topical 5-fluorouracil (5-FU) is an effective treatment for actinic keratoses (AK), a highly prevalent condition among elderly populations, but it is often associated with unpredictable retail prices and high out-of-pocket costs. One online pharmacy offers branded prescription medications at fixed, low prices, but it may be less accessible to older patients for numerous reasons. OBJECTIVE: To determine if the number of patients receiving topical 5-FU from an online pharmacy is proportionate to the national data on expected payment types for patients prescribed topical 5-FU for AK. METHODS: We conducted a cross-sectional study using weighted pooled data from the National Ambulatory Medical Care Survey (NAMCS) on topical 5-FU prescriptions for AK from 2007-2016. Data regarding online pharmacy use were provided by Dermatology.com for the year 2019. RESULTS: Among patients with AK prescribed topical 5-FU, the most prevalent payment source was Medicare (54%) followed by private insurance (40%). On the online pharmacy, the majority of patients had commercial insurance (71%) followed by Medicaid (12%). LIMITATIONS: Data from Dermatology.com are limited. CONCLUSIONS: Lower-cost medications from the online pharmacy site may improve adherence and outcomes in older adults and decrease total cost associated with AK treatment. However, the online pharmacy is underutilized by this population. J Drugs Dermatol. 2020;19(4): doi:10.36849/JDD.2020.4690.

Treatment Goals in Psoriasis: Which Outcomes Matter Most?

Psoriasis is a chronic immune-mediated inflammatory disease that predominantly affects the skin and joints. Its detrimental effects on the physical, psychosocial, and emotional well-being of patients leads to a significant reduction in quality of life (QoL). The goals of treatment focus on decreasing disease severity and improving QoL for patients; accomplishing these goals requires physicians to understand both the full impact of the disease on a patient's life and the outcomes that matter most to patients. The use of outcome measures, both physician- and patient-reported, can assist clinicians in evaluating the disease burden and its effect on QoL and in identifying patient preferences for treatment, ultimately enhancing quality of care. However, current outcome measures have many limitations and do not adequately capture patients' needs and priorities. Nevertheless, physicians treating patients with psoriasis are encouraged to utilize these instruments while remaining cognizant of each of their limitations. As there is no consensus on an outcome measure that fully encompasses the complexities of psoriasis and its impact on patients, instruments that are appropriate and applicable to dermatologists and their patients should be developed.

Emerging systemic drugs in the treatment of plaque psoriasis.

INTRODUCTION: Psoriasis is a common, chronic inflammatory skin condition that affects 2-3% of the US population and represents a large psychosocial burden for patients. Over the last decade, highly effective targeted therapies for psoriasis have been developed - namely, those targeting interleukin (IL)-17 and IL-23. The success of biologic agents targeting IL-17 and IL-23 underscores the importance of the IL-23/T helper (Th)17 cell axis in psoriasis pathogenesis. Oral small molecule drugs - such as Janus kinase (JAK) inhibitors, tyrosine kinase 2 (TYK2) inhibitors, and fumaric acid esters (FAEs) - are also being investigated for the treatment of psoriasis. AREAS COVERED: This article reviews systemic biologic and oral small molecule drugs currently undergoing clinical trials for the treatment of plaque psoriasis. EXPERT OPINION: Many patients with psoriasis have mild disease, and many with mild disease do not seek medical care for their condition. Many patients with mild disease could be adequately treated with topical treatments and phototherapy; however, adherence and feasibility have often been an issue with these treatment types. There seems to be limited room for development of novel biologics, as the existing ones are extraordinarily safe, effective, and convenient with few injections. Patients would prefer a safe, effective oral treatment; however, JAK inhibitors seem unlikely to fill this role completely.

Pharmacological management of atopic dermatitis in the elderly.

INTRODUCTION: The prevalence of atopic dermatitis (AD) in geriatric populations of industrialized countries is currently estimated at 3-4% and continues to increase. AD is associated with significant morbidity, increased susceptibility to infection, and symptoms of pruritus and pain. Treatments may negatively affect elderly patients; thus, plans should be optimized for this population. AREAS COVERED: This review summarizes treatment options for AD in the elderly. A systematic review of the literature was conducted using the key terms atopic dermatitis, elderly, geriatric, systemic therapy, therapy, and topical therapy in PubMed. Searches yielded articles on skincare management and topical and systemic pharmacotherapies. EXPERT OPINION: Proper use of moisturizer is crucial in all patients with AD. Topical corticosteroids are commonly prescribed; however, they carry an increased risk of adverse events such as skin atrophy. Systemic corticosteroids should be avoided in elderly patients due to questionable efficacy and increased adverse events. Topical calcineurin inhibitors and crisaborole are similarly efficacious with an excellent safety profile. Cyclosporine, azathioprine, methotrexate, and mycophenolate mofetil are systemic agents available for the treatment of refractory AD; however, insufficient data exist to indicate the superiority of any one agent. Dupilumab is a safe and efficacious injectable therapy in elderly patients.