psoriasis
218690529
Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review.
Importance Approximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders. Observations Plaque psoriasis is the most common variant of psoriasis. The most rapid advancements addressing plaque psoriasis have been in its pathogenesis, genetics, comorbidities, and biologic treatments. Plaque psoriasis is associated with a number of comorbidities including psoriatic arthritis, cardiometabolic diseases, and depression. For patients with mild psoriasis, topical agents remain the mainstay of treatment, and they include topical corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics. The American Academy of Dermatology National Psoriasis Foundation guidelines recommend biologics as an option for first line treatment of moderate to severe plaque psoriasis because of their efficacy in treating it and acceptable safety profiles. Specifically, inhibitors to tumor necrosis factor a (TNF a) include etanercept, adalimumab, certolizumab, and infliximab. Other biologics inhibit cytokines such as the p40 subunit of the cytokines IL 12 and IL 13 (ustekinumab) IL 17 (secukinumab, ixekizumab, bimekizumab, and brodalumab) and the p19 subunit of IL 23 (guselkumab, tildrakizumab, risankizumab, and mirikizumab) Biologics that inhibit TNF a, p40IL 12/23, and IL 17 are also approved for the treatment of psoriatic arthritis. Oral treatments include traditional agents such as methotrexate, acitretin, cyclosporine, and the advanced small molecule apremilast, which is a phosphodiesterase 4 inhibitor. The most commonly prescribed light therapy used to treat plaque psoriasis is narrowband UV B phototherapy. Conclusions and Relevance Psoriasis is an inflammatory skin disease that is associated with multiple comorbidities and substantially diminishes patients' quality of life. Topical therapies remain the cornerstone for treating mild psoriasis. Therapeutic advancements for moderate to severe plaque psoriasis include biologics that inhibit TNF a, p40IL 12/23, IL 17, and p19IL 23, as well as an oral phosphodiesterase 4 inhibitor.
JAMA
April W Armstrong Charlotte Read
73478106
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.
Journal of the American Academy of Dermatology
Alan Menter Bruce Strober Daniel H Kaplan Dario Kivelevitch Elizabeth Farley Prater Benjamin K Stoff April W Armstrong Cody J Connor Kelly M Cordoro Dawn Marie R Davis B E Elewski Joel M Gelfand Kenneth B Gordon Alice B Gottlieb Arthur Kavanaugh Matthew Kiselica Neil J Korman Daniela Kroshinsky Mark G Lebwohl Craig L Leonardi Jason Lichten Henry W Lim Nehal N Mehta Amy S Paller Sylvia L Parra Arun L Pathy Reena N Rupani Michael P Siegel Emily B Wong Jashin J Wu Vidhya Hariharan Craig A Elmets
85515260
Psoriasis Pathogenesis and Treatment
Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL 23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well established widely available therapies and novel targeted drugs.
International journal of molecular sciences
Adriana Rendon Knut Schakel
174805576
Systemic pharmacological treatments for chronic plaque psoriasis: a network meta analysis.
Background Psoriasis is an immune mediated chronic inflammatory disease that affects the skin and/or joints of a person. Although the exact cause of psoriasis has not been determined, it is thought to be caused by a combination of genetic and environmental factors. Environmental factors, including stress, injury and infections, trigger an inflammatory immune response involving dendritic cells, T cells, keratinocytes, neutrophils and cytokines in those predisposed to thedisease. Theprevalenceof thedisease ranges from 0.91% in the United States to 8.5% inNorway. There are several types of psoriasis, including plaque, pustular, inverse and erythrodermic, with plaque psoriasis the most common, affecting 90% of sufferers. The signs and symptoms of this type of psoriasis include raised erythematous and well demarked areas of inflamed skin, covered by silvery white, scaly skin, typically located on the elbows, knees, scalp, lower back and periumbilical region. The severity of symptoms varies, ranging from exacerbations of the disease that can involve the whole body, to minor localized patches of inflammation and remission. A psychological impact has also been reported, with impairment of quality of life and stigma associated with symptomology. No cure exists for psoriasis and treatment involves symptommanagement. Treatment regimes are, typically long term in nature and involve two discrete phases: induction therapy, leading to short term remission and maintenance therapy, leading to long term remission. Topical agents are the first line of treatment; however in moderate to severe cases a second line therapy may be required, for example phototherapy and the use of conventional systemic agents such as cyclosporine or methotrexate. Progress in physiological comprehension led to the emergence of biologic treatments and offered new therapeutic possibilities for patients. Biologic treatments work by suppressing the immune system.
International journal of evidence based healthcare
Jacqueline Pich
51679072
Psoriasis: Which therapy for which patient: Psoriasis comorbidities and preferred systemic agents.
Psoriasis is a systemic inflammatory disease associated with increased risk of comorbidities, such as psoriatic arthritis, Crohn's disease, malignancy, obesity, and cardiovascular diseases. These factors have a significant impact on the decision to use one therapy over another. The past decade has seen a paradigm shift in our understanding of the pathogenesis of psoriasis that has led to identification of new therapeutic targets. Several new drugs have gained approval by the US Food and Drug Administration, expanding the psoriasis armamentarium, but still a large number of patients continue to be untreated or undertreated. Treatment regimens for psoriasis patients should be tailored to meet the specific needs based on disease severity, the impact on quality of life, the response to previous therapies, and the presence of comorbidities. The first article in this continuing medical education series focuses on specific comorbidities and provides insights to choose appropriate systemic treatment in patients with moderate to severe psoriasis.
Journal of the American Academy of Dermatology
Shivani B Kaushik Mark G Lebwohl
49337268
Prevalence of psoriatic arthritis in patients with psoriasis: A systematic review and meta analysis of observational and clinical studies
Background: Wide ranging prevalence estimates of psoriatic arthritis (PsA) in patients with psoriasis have been reported. Objectives: To assess the prevalence and incidence of PsA in patients with psoriasis. Methods: Two authors independently searched 3 databases for studies reporting on the prevalence or incidence of PsA in patients with psoriasis. A proportion meta analysis was performed to calculate the pooled proportion estimates of PsA in patients with psoriasis. Results: A total of 266 studies examining 976,408 patients with psoriasis were included. Overall, the pooled proportion (95% confidence interval [CI] of PsA among patients with psoriasis was 19.7% (95% CI, 18.5% 20.9% In children and adolescents <18 years of age) the pooled prevalence was 3.3% (95% CI, 2.1% 4.9% The PsA prevalence was 22.7% (95% CI, 20.6% 25.0% in European patients with psoriasis, 21.5% (95% CI, 15.4% 28.2% in South American patients with psoriasis, 19.5% (95% CI, 17.1% 22.1% in North American patients with psoriasis, 15.5% (95% CI, 0.009% 51.5% in African patients with psoriasis, and 14.0% (95% CI, 95% CI, 11.7% 16.3% in Asian patients with psoriasis. The prevalence of PsA was 23.8% (95% CI, 20.1% 27.6% in studies in which the Classification Criteria for Psoriatic Arthritis were applied. The incidence of PsA among patients with psoriasis ranged from 0.27 to 2.7 per 100 person years. Limitations: Between study heterogeneity may have affected the estimates. Conclusions: We found that 1 in 4 patients with psoriasis have PsA. With the growing recognition of the Classification Criteria for Psoriatic Arthritis, more homogenous and comparable prevalence estimates are expected to be reported.
Journal of the American Academy of Dermatology
Farzad Alinaghi Monika Calov Lars Erik Kristensen Dafna D Gladman Laura C Coates Denis Jullien Alice B Gottlieb Paolo Gisondi Jashin J Wu Jacob Pontoppidan Thyssen Alexander Egeberg
75135579
Inhibition of the Interleukin 36 Pathway for the Treatment of Generalized Pustular Psoriasis.
Interleukin 36 Blockade in Pustular Psoriasis Seven patients with pustular psoriasis, three with mutations in IL36RN, were treated with a monoclonal antibody against interleukin 36 receptor and had.
The New England journal of medicine
Herve Bachelez Siew Eng Choon Slaheddine Marrakchi A D Burden Tsen-Fang Tsai Akimichi Morita Hamida Turki David B Hall Michael Shear Patrick Baum Steven J Padula Christian Thoma
51678965
Psoriasis: Which therapy for which patient: Focus on special populations and chronic infections.
Despite the availability of several new systemic agents for psoriasis treatment, choosing the right therapy in certain patient populations can be challenging. There are few up to date reviews on systemic drugs for moderate to severe psoriasis in pregnant and pediatric patients and in patients with concomitant chronic infections, such as hepatitis, HIV, and latent tuberculosis. These groups are usually excluded from clinical trials, and much of the available evidence is based on anecdotal case reports and case series. As a chronic disease, psoriasis requires long term treatment, and there are concerns of adverse maternal fetal outcomes, long term side effects in children, and the reactivation of latent infections with the use of systemic agents in these patients. The second article in this continuing medical education series provides insights for choosing appropriate systemic agents for treating moderate to severe psoriasis in pregnant and pediatric patients and in the setting of chronic infections, such as hepatitis, HIV, and latent tuberculosis.
Journal of the American Academy of Dermatology
Shivani B Kaushik Mark G Lebwohl
73476634
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.
Journal of the American Academy of Dermatology
Craig A Elmets Craig L Leonardi Dawn Marie R Davis Joel M Gelfand Jason Lichten Nehal N Mehta April W Armstrong Cody J Connor Kelly M Cordoro B E Elewski Kenneth B Gordon Alice B Gottlieb Daniel H Kaplan Arthur Kavanaugh Dario Kivelevitch Matthew Kiselica Neil J Korman Daniela Kroshinsky Mark G Lebwohl Henry W Lim Amy S Paller Sylvia L Parra Arun L Pathy Elizabeth Farley Prater Reena N Rupani Michael P Siegel Benjamin K Stoff Bruce Strober Emily B Wong Jashin J Wu Vidhya Hariharan Alan Menter
21301200
Secukinumab in plaque psoriasis results of two phase 3 trials.
BACKGROUND Interleukin 17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti interleukin 17A monoclonal antibody, in patients with moderate to severe plaque psoriasis. METHODS In two phase 3, double blind, 52 week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks) placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly) The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area and severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5 point modified investigator's global assessment (coprimary end points) RESULTS The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators) The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators) The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept. CONCLUSIONS Secukinumab was effective for psoriasis in two randomized trials, validating interleukin 17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.
The New England journal of medicine
Richard G B Langley B E Elewski Mark G Lebwohl Kristian Reich Christopher E M Griffiths Kim A Papp Lluis Puig Hidemi Nakagawa Lynda Spelman Bardur Sigurgeirsson Enrique Rivas Tsen-Fang Tsai Norman R Wasel Stephen K Tyring Thomas Salko Isabelle Hampele Marianne Notter Alexander Karpov Silvia Helou Charis Papavassilis