Journal of Clinical and Aesthetic Dermatology

Psoriasis and Cutaneous Supplement 2016

An evidence-based, peer-reviewed journal for practicing clinicians in the field of dermatology

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U pdates on Psoriasis and Cutaneous Oncology: Proceedings from the 2016 MauiDerm Meeting [ S E P T E M B E R 2 0 1 6 • V O L U M E 9 • N U M B E R 9 ] S U P P L E M E N T T O T H E J O U R N A L O F C L I N I C A L A N D A E S T H E T I C D E R M AT O L O G Y S 1 3 NCT01594333, is testing the hypothesis that methotrexate will lower the risk of major vascular events in patients with a history of myocardial infarction (MI) or metabolic syndrome. In clinical practice, dermatologists should consider that severe psoriasis implies an elevated cardiovascular risk. While patients with severe psoriasis should be screened for hypertension, diabetes, and standard cardiovascular risk, less than half of U.S. dermatologists surveyed report performing such screenings. 79 The prevalence of uncontrolled hypertension in the non- psoriasis population is 51.6 versus 53.9 percent of psoriasis patients overall; in patients with severe psoriasis, uncontrolled hypertension prevalence is 59.5 percent. 80,81 A study of 693 Danish patients with severe psoriasis found cardiovascular risk factors under-treated and that these patients were less likely than matched control patients to receive pharmacotherapy for cardiovascular risk factors. 8 2 Emerging comorbidity associations with psoriasis include conditions such as sleep apnea and other sleep disorders, nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary disease (COPD), adverse infectious disease outcomes, chronic and end-stage renal disease, peptic ulcer disease, and sexual dysfunction. 44,83–87 Moderate-to-severe psoriasis has been implicated as a risk factor in chronic kidney disease (CKD). Patients with moderate-to-severe psoriasis have a two-fold risk of chronic kidney disease compared to control patients and have a greater than four-fold risk of needing dialysis. 88 These risks are independent of other known risk factors, such as diabetes, hypertension, and potentially nephrotoxic pharmacotherapy. 88,89 Moreover, moderate- to-severe patients have a two-fold increased risk of death from kidney disease versus controls. 90 The prevalence of CKD increases with the severity of psoriasis. The association between psoriasis and cancer is an ongoing subject for research. A recent study of 937,716 control patients matched with 198,366 psoriasis patients (186,076 had mild and 12,290 had moderate-to-severe psoriasis) found an association between psoriasis and incident lymphoma and lung cancer, but not for breast, colon, or prostate cancer or leukemia. 91 Dermatologists should advise their psoriasis patients to keep up to date on appropriate cancer screenings particularly when considering immune modulating treatments, which may theoretically impact the risk of cancer as described in FDA prescribing information. It has long been known that psoriasis is associated with depression, anxiety, and other mood disorders. There is some evidence suggesting that cognitive- behavioral therapies and meditation may enhance the patient's response to psoriasis treatment. 92,93 Finally, dermatologists should monitor psoriasis patients closely for signs and symptoms of psoriatic arthritis. These symptoms include morning joint stiffness, joint pain that improves upon activity, swollen or tender joints, dactylitis, and enthesitis. When treating psoriasis, prescribing decisions should consider potential comorbidities. For example, TNF inhibitors may be effective in treating psoriasis, but are contraindicated in patients with multiple sclerosis. IL-17 should generally not be prescribed to patients with active Crohn's disease. Other important prescribing considerations should include obesity (weight-based dosing), rapid onset of action, and long-term persistence. Important Psoriasis Papers Published in 2015 A literature search for "psoriasis" work published in 2015 turns up a wealth of material, including articles published in high-impact international medical journals, such as the Journal of the American Medical Association, The New England Journal of Medicine, and Lancet, among others. Many of these articles focus on our emerging understanding of the IL-23/Th17 immunologic pathway, which is critical in psoriasis pathogenesis. With this wealth of important new findings, a few stand out in terms of clinical trial results, new work in comorbidities, immunology highlights, and recent important clinical reviews. Clinical trials. The results of eight important psoriasis trials were published in 2015 (Table 6). Tildrakizumab is a monoclonal antibody that targets the IL-23 p19 subunit and was the subject this year of a major Phase 1 and Phase 2 trial. The novel agent, BI- 655066, or risankizumab, is a fully human immunoglobulin G1(IgG1) mAb specific molecule for the IL-23 p19 subunit. Results from this Phase 1 study were particularly noteworthy and generated national news interest in that many patients achieved excellent results that endured over a year following one single intravenous injection of the agent. 28 Another important Phase 2 study by Gordon et al, published in The New England Journal of Medicine, evaluated several dosing schemes for guselkumab (CNTO-1959), an anti-IL-23 monoclonal antibody. 26 Phase 3 studies of note in 2015 evaluated the anti-IL-17A/17RA blockers, ixekizumab (UNCOVER-2 and UNCOVER-3 studies) and brodalumab. 31,94 Ixekizumab is a humanized monoclonal antibody that selectively blocks IL-17A. Comorbidities. The subject of psoriasis comorbidities continues to be an important area of ongoing exploration with significant publications appearing in 2015 with respect to cardiovascular comorbidities, psoriatic arthritis, and infections. In a murine study, it was found that mice with long- term psoriasis-like disease were at greater risk of developing thromboses than mice with short-term psoriasis disease, suggesting that it is chronic rather than acute skin-specific inflammation that promotes thrombosis in mice. 97 Cardiovascular comorbidities were further explored in a population-based cross-section study from the United Kingdom that found that uncontrolled hypertension (defined as systolic pressure of 140mmHg or greater and diastolic pressure of

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