Orismilast in moderate-to-severe psoriasis: Efficacy and safety from a 16-week, randomized, double-blinded, placebo-controlled, dose-finding, and phase 2b trial (IASOS).

BACKGROUND: Orismilast is a novel oral phosphodiesterase-4 (PDE4) B/D inhibitor being investigated as a potential treatment for moderate-to-severe psoriasis. OBJECTIVE: To evaluate efficacy and safety of orismilast modified-release formulation in moderate-to-severe psoriasis. METHODS: This multicenter, randomized (1:1:1:1 to 20, 30, 40 mg orismilast or placebo, twice daily), double-blinded, placebo-controlled, parallel-group, phase 2b, 16-week, dose-ranging study evaluated orismilast in adults with moderate-to-severe plaque psoriasis (NCT05190419). Efficacy end points were analyzed using multiple imputation. RESULTS: Of 202 randomized patients, baseline characteristics were balanced across arms, except greater severe disease proportions for orismilast vs placebo. Orismilast showed significant improvements in the primary end point, percentage change in Psoriasis Area and Severity Index (PASI), from baseline to week 16 (orismilast -52.6% to -63.7% and placebo, -17.3%; all P <.001). Greater proportions receiving orismilast achieved PASI75 (39.5%-49.0%; P <.05) and PASI90 (22.0%-28.3%; P <.05 for 20 and 40 mg) vs placebo (PASI75, 16.5% and PASI90, 8.3%) at week 16. Safety findings were as expected with PDE4 inhibition; dose-dependent tolerability effects observed. LIMITATIONS: Small sample size, disease severity imbalance between groups, limited duration and diversity in study population. CONCLUSION: Orismilast demonstrated greater efficacy vs placebo and a safety profile in line with PDE4 inhibition.

Prospective cohort study of psoriatic arthritis risk in patients with psoriasis in a real-world psoriasis registry.

BACKGROUND: The characteristics that predict the onset of psoriatic arthritis (PsA) among patients with psoriasis (PsO) may inform diagnosis and treatment. OBJECTIVE: To develop a model to predict the 2-year risk of developing PsA among patients with PsO. METHODS: This was a prospective cohort study of patients in the CorEvitas Psoriasis Registry without PsA at enrollment and with 24-month follow-up. Unregularized and regularized logistic regression models were developed and tested using descriptive variables to predict dermatologist-identified PsA at 24 months. Model performance was compared using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 1489 patients were included. Nine unique predictive models were developed and tested. The optimal model, including Psoriasis Epidemiology Screening Tool (PEST), body mass index (BMI), modified Rheumatic Disease Comorbidity Index, work status, alcohol use, and patient-reported fatigue, predicted the onset of PsA within 24 months (AUC = 68.9%, sensitivity = 82.9%, specificity = 48.8%). A parsimonious model including PEST and BMI had similar performance (AUC = 68.8%; sensitivity = 92.7%, specificity = 36.5%). LIMITATIONS: PsA misclassification bias by dermatologists. CONCLUSION: PEST and BMI were important factors in predicting the development of PsA in patients with PsO over 2 years and thereby foundational for future PsA risk model development.

Hidradenitis suppurativa: Epidemiology, clinical presentation, and pathogenesis.

Hidradenitis suppurativa (HS) is an inflammatory disorder that is characterized by chronic deep-seated nodules, abscesses, fistulae, sinus tracts, and scars in the axilla, inguinal area, submammary folds, and perianal area. This disfiguring condition is accompanied by pain, embarrassment, and a significantly decreased quality of life. Although the mechanism of HS has not been entirely elucidated, lesion formation is believed to center around follicular hyperkeratosis within the pilosebaceous-apocrine unit. Recent research has provided new insight into the role of cytokines in the pathogenesis of HS, helping close some existing knowledge gaps in the development of this condition. The first article in this continuing medical education series reviews HS epidemiology, clinical presentation, and classification. We also provide an update on the most recent understanding of HS pathogenesis, including the central role of inflammatory cytokines and other contributing factors, such as genetics, hormones, and pathogenic microorganisms.

Hidradenitis suppurativa: Current and emerging treatments.

The treatment of hidradenitis suppurativa (HS) has remained challenging because of the many knowledge gaps regarding etiology. However, recent studies into the pathogenesis of HS have enabled the investigation of newer therapies. The second article in this continuing medical education series reviews the evidence for established therapies for HS, including anti-inflammatories, antibiotics, and surgery. New and emerging therapies that specifically target cytokines involved in HS pathogenesis will be covered. The potential therapeutic roles of anticytokine therapies, including both the expanded application of existing molecules as well as the specific development of novel therapies for HS are discussed. With increased attention on HS and with numerous clinical trials currently underway, we hope that the variety of treatment options for HS will be expanded.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis in pediatric patients.

Psoriasis is a chronic, multisystem, inflammatory disease that affects approximately 1% of children, with onset most common during adolescence. This guideline addresses important clinical questions that arise in psoriasis management and provides evidence-based recommendations. Attention will be given to pediatric patients with psoriasis, recognizing the unique physiology, pharmacokinetics, and patient-parent-provider interactions of patients younger than 18 years old. The topics reviewed here mirror those discussed in the adult guideline sections, excluding those topics that are irrelevant to, or lack sufficient information for, pediatric patients.

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 2% of the world's population. In this guideline, we focus the discussion on systemic, nonbiologic medications for the treatment of this disease. We provide detailed discussion of efficacy and safety for the most commonly used medications, including methotrexate, cyclosporine, and acitretin, and provide recommendations to assist prescribers in initiating and managing patients on these treatments. Additionally, we discuss newer therapies, including tofacitinib and apremilast, and briefly touch on a number of other medications, including fumaric acid esters (used outside the United States) and therapies that are no longer widely used for the treatment of psoriasis (ie, hydroxyurea, leflunomide, mycophenolate mofetil, thioguanine, and tacrolimus).

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy.

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world's population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with awareness and attention to comorbidities.

Psoriasis is a chronic, inflammatory, multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations on the basis of available evidence.

Joint AAD-NPF guidelines of care for the management and treatment of psoriasis with biologics.

Psoriasis is a chronic, inflammatory multisystem disease that affects up to 3.2% of the US population. This guideline addresses important clinical questions that arise in psoriasis management and care, providing recommendations based on the available evidence. The treatment of psoriasis with biologic agents will be reviewed, emphasizing treatment recommendations and the role of the dermatologist in monitoring and educating patients regarding benefits as well as associated risks.

Dupilumab in the Treatment of Dyshidrosis: A Report of Two Cases.

Dupilumab (Dupixent, Regeneron Pharmaceuticals and Sanofi Genzyme) is a novel biologic medication recently approved by the FDA for the treatment of moderate-to-severe atopic dermatitis in adults who have not achieved adequate control with topical medications. Dyshidrotic eczema is a distinct entity, often considered on the spectrum of atopic dermatitis, that primarily effects the palms and soles; it is often associated with considerable morbidity yet is frequently challenging to treat. We report two cases of recalcitrant dyshidrotic eczema treated successfully with dupilumab at standard dosing. Further studies to establish the efficacy of dupilumab in the treatment of dyshidrosis are warranted.

J Drugs Dermatol. 2018;17(3):355-356.

Effects of tofacitinib on cardiovascular risk factors and cardiovascular outcomes based on phase III and long-term extension data in patients with plaque psoriasis.

BACKGROUND: Psoriasis is a systemic inflammatory condition that is associated with a higher risk of cardiovascular (CV) disease. Tofacitinib is being investigated as a treatment for psoriasis. OBJECTIVE: We sought to evaluate the effects of tofacitinib on CV risk factors and major adverse CV events (MACEs) in patients with plaque psoriasis. METHODS: Changes in select CV risk factors and the incidence rate (IR) of MACEs were evaluated in patients who were treated with tofacitinib. RESULTS: Tofacitinib treatment was associated with small, dose-dependent increases in total cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol, while the total/HDL cholesterol ratio was unchanged. There were no changes in blood pressure and glycated hemoglobin levels; C-reactive protein levels decreased. The IRs of a MACE were low and similar for both tofacitinib doses. Among 3623 subjects treated with tofacitinib, the total patient-years of exposure was 5204, with a median follow-up of 527 days, and the IR of MACEs was 0.37 (95% confidence interval, 0.22-0.57) patients with events per 100 patient-years. LIMITATIONS: There was relatively short follow-up time for patients who had MACEs. CONCLUSIONS: While treatment with tofacitinib is associated with a small increase in cholesterol levels, the total/HDL cholesterol ratio does not change, there are no unfavorable changes in several CV risk factors, and the incidence of MACEs is low.

Comparative effectiveness of biologic agents for the treatment of psoriasis in a real-world setting: Results from a large, prospective, observational study (Psoriasis Longitudinal Assessment and Registry [PSOLAR]).

BACKGROUND: Comparing effectiveness of biologics in real-world settings will help inform treatment decisions. OBJECTIVES: We sought to compare therapeutic responses among patients initiating infliximab, adalimumab, or etanercept versus ustekinumab during the Psoriasis Longitudinal Assessment and Registry (PSOLAR). METHODS: Proportions of patients achieving a Physician Global Assessment score of clear (0)/minimal (1) and mean decrease in percentage of body surface area with psoriasis were evaluated at 6 and 12 months. Adjusted logistic regression (Physician Global Assessment score 0/1) and analysis of covariance (percentage of body surface area with psoriasis) were performed to determine treatment factors associated with effectiveness. RESULTS: Of 2541 new users on registry, 2076 had efficacy data: ustekinumab (n = 1041), infliximab (n = 116), adalimumab (n = 662), and etanercept (n = 257). Patients receiving tumor necrosis factor-alpha(-α) inhibitors were significantly less likely to achieve Physician Global Assessment score 0/1 versus ustekinumab (infliximab [odds ratio {OR} 0.396, P < .0001], adalimumab [OR 0.686, P = .0012], etanercept [OR 0.554, P = .0003] at 6 months and infliximab [OR 0.449, P = .0040] at 12 months). Mean decrease in percentage of body surface area with psoriasis was significantly greater for ustekinumab versus adalimumab (point estimate 1.833, P = .0020) and etanercept (point estimate 3.419, P < .0001) at 6 months and versus infliximab (point estimate 3.945, P = .0005) and etanercept (point estimate 2.778, P = .0007) at 12 months. LIMITATIONS: Treatment selection bias and limited data for doing adjustments are limitations. CONCLUSIONS: In PSOLAR, effectiveness of ustekinumab was significantly better versus all 3 tumor necrosis factor-α inhibitors studied for the majority of comparisons at 6 and 12 months.

Treatment of Moderate to Severe Pediatric Psoriasis: A Retrospective Case Series.

BACKGROUND: Psoriasis has an estimated prevalence of 0.5% to 2.0% in children. There is a paucity of data regarding the management and safety of treatments currently available for children with moderate to severe psoriasis. The aim of this study was to evaluate the treatment response and safety of systemic therapies used to manage moderate to severe pediatric psoriasis in a single referral center. Despite a small sample size, it was hypothesized that multiple therapeutics used for adult psoriasis would have a similar side-effect profile and positive disease response when used in a pediatric population. METHODS: A retrospective case series evaluated 51 children with moderate to severe psoriasis treated with systemic therapies for adverse event occurrence and for disease response using a 5-point Physician Global Assessment scale. RESULTS: Fifty-one patients, some of whom used multiple treatment options, produced 80 treatment data points. Adverse events were reported in 29 of these 80 treatments, with most being minor, subjective side effects. Overall, the most commonly reported side effect was fatigue, which was reported in 7.5% of treatments. Because of the small sample size, the data collected are limited and may not represent a comprehensive safety profile, nor do they allow comparison of efficacy between therapies. This case series found that biologic and immunomodulating therapies provide well-tolerated treatments with positive disease response for moderate to severe pediatric psoriasis. CONCLUSION: Although sample size and study design limit the data from this study, the study provides some guidance where little exists and helps to support the use of these treatments in this setting.

New Therapies for Psoriasis.

Among the newer medications for treating psoriasis are the interleukin-17A inhibitor secukinumab and the phosphodiesterase 4 inhibitor apremilast. Secukinumab offers a level of efficacy greater than that of the tumor necrosis factor-α inhibitor adalimumab. Apremilast is associated with lower levels of efficacy than the biologic therapies for psoriasis. Apremilast may cause diarrhea and nausea and is associated with weight loss and rare instances of depression. Semin Cutan Med Surg 35(supp4):S71-S73.

Why Biologic Therapies Sometimes Lose Efficacy.

Biologic therapies for psoriasis are associated with loss of response over time. Immunogenicity, suboptimal dosing, low serum drug levels, and intermittent or episodic therapy have been documented as explanations for this phenomenon. Use of an immunomodulatory agent can reduce the risk of immunogenicity and improve clinical response.

The Use of Methotrexate, Alone or in Combination With Other Therapies, for the Treatment of Palmoplantar Psoriasis.

Palmoplantar psoriasis is a chronic debilitating type of psoriasis. Treatment options for this disease are poorly studied. This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis. The findings demonstrate that methotrexate is a relatively well-tolerated and effective treatment for palmoplantar psoriasis, amenable as either monotherapy or in combination with other systemic agents.

The use of self-administered subcutaneous methotrexate for the treatment of psoriasis.

For nearly 5 decades, methotrexate has been the backbone of moderate-to-severe psoriasis treatment. The benefits of methotrexate therapy include reliable efficacy, low cost, relative ease of administration, and its usefulness as part of combination therapy regimens, making it a drug of choice for treating psoriasis. While methotrexate can be administered orally, intravenously, or intramuscularly, the self-administered subcutaneous use of the drug is the most advantageous route. Subcutaneous methotrexate is associated with fewer adverse events and higher absorption rates, accompanied by bioavailability that is both linear and predictable throughout the range of possible doses. In addition, the subcutaneous route, when compared with oral administration, facilitates improved efficacy by promoting higher intracellular levels of long-chain methotrexate polyglutamates. Taken together, these features allow patients the highest probability of a successful therapeutic experience. Subcutaneous methotrexate should be considered a viable option for the appropriate patient with moderate-to-severe psoriasis.

Methotrexate and cyclosporine in psoriasis revisited.

Methotrexate and cyclosporine - as monotherapy or in combination with biologics or other drugs - still have an important place in the roster of therapeutic options for patients with psoriasis. These medications are safe and effective in carefully selected patients and with careful monitoring. Contraindications are discussed. Data on efficacy and adverse effects-particularly hepatoxicity - are reviewed, and recommendations for monitoring are addressed.

Understanding therapeutic pathways and comorbidities in psoriasis.

Psoriasis is now recognized as an immunologically mediated systemic disease that may be expressed in cutaneous and joint symptoms. Medications that were once thought to control psoriasis by reducing keratinocyte proliferation are now known to act on immunologic pathways. In recent years, the emerging understanding of immunologic pathways in psoriasis has resulted in the use of biologic medications (eg, inhibitors of tumor necrosis factor) to treat psoriasis. More recently, other pathophysiologic pathways have been identified that have the potential to expand the therapeutic armamentarium. Other avenues of research within the past decade have demonstrated that a range of health risks and comorbid inflammatory diseases are associated with psoriasis, and they have the potential to increase morbidity and mortality and adversely affect quality of life.