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 1 3.1 percent of foam and 1.9 percent of placebo patients. 38 No significant changes in albumin-corrected serum calcium levels or the ratio of urinary calcium to creatinine were observed. In a randomized investigator-blinded trial of 376 plaque psoriasis patients, treatment arms compared two fixed combination products of calcipotriene plus betamethasone dipropionate in aerosol foam versus ointment. Patients were randomized into one of four groups for four-weeks of once daily treatment: calcipotriene plus betamethasone dipropionate aerosol foam, foam vehicle, calcipotriene betamethasone dipropionate ointment, and ointment vehicle. 39 Treatment success, defined as being clear or almost clear with at least a two-step improvement, occurred among significantly more aerosol foam combination product patients than ointment patients (54.6% vs. 43.0%, p=0.025). Rapid and continuous relief of itching was reported with both active treatments. The MUSE Phase 2 trial evaluated product safety in 35 patients with extensive psoriasis (defined as body surface area of 15–30%) treated for four weeks with calciprotiol and betamethasone dipropionate foam; no evidence of effect on calcium metabolism was found, no serious adverse events were reported, and the product was described as generally well-tolerated. None of the patients exhibited adrenal suppression, as indicated by a 30-minute, post-stimulation cortisol level of ≤18μg/dL at Week 4. 4 0 Tazarotene is a familiar topical retinoid product commercially available on 0.1% and 0.05% cream and gel formulations. It is a pregnancy Category X drug and causes adverse events in about 10 to 30 percent of patients, including pruritus, burning, stinging, erythema, exacerbation of psoriasis, irritation, and skin pain. Nevertheless, when tazarotene 0.1% is combined with topical corticosteroids, tazarotene's efficacy is enhanced while side effects are minimized. 41 A placebo-controlled clinical trial of a tazarotene 0.045% product combined with a lotion formulation of halobetasol propionate 0.01% (product is currently named IDP-118) is currently underway in adult patients with moderate-to-severe psoriasis. Other important ongoing clinical trials include a trial of a product called GSK-2894512, a small molecule being tested in 0.5% and 1.0% concentrations in two different application frequencies (once versus twice daily) in a randomized, vehicle-controlled, six-arm, parallel-group, dose-finding, 12-week study of patients with moderate- to-severe plaque psoriasis (excluding psoriasis on the scalp). There is still a significant role for topical therapy in the treatment of psoriasis and new combination approaches and dosing regimens may further enhance their efficacy and tolerability. Novel small molecules are also in the pipeline for topical applications: there are studies of a phosphodiesterase 4 (PDE4) inhibitor ointment, an integrin inhibitor cream, a JAK-1/JAK-2 inhibitor cream (ruxolitinib), a tyrosine kinase inhibitor cream and ointment formulation, and a dihydrofolate reductase inhibitor (methotrexate) proprietary vehicle. 42 Update on Psoriasis Comorbidities The new millennium has seen a tremendous upsurge in our awareness of psoriasis as a disease, the critical importance of the Th17 pathway, biologic treatments targeting T-cells, TNF, IL 12/23, and IL-17, the genetic component of psoriasis, and its many comorbid conditions. There has been a marked increase in literature on the important topic of psoriasis comorbidities lately. The old paradigm that psoriasis is "just a skin disease" has given way to our understanding of psoriasis as a systemic disease. On December 30, 2015, results from a search on the Scopus database with the keywords "psoriasis and cardiovascular disease" indicate the marked increase in the quantity of publications on this topic from 1965 to 2015. The phenotypically diverse conditions of diabetes mellitus type II, coronary artery disease, myocardial infarction, and obesity are all comorbid with psoriasis and share similar pathologic changes, such as chronic inflammation, angiogenesis, oxidative stress, and certain genetic factors. Indeed, the comorbidities paradigm for psoriasis would include genes and loci (PSORS2/3/4, CDKAL1, ApoE4, and TNFAIP32, environmental factors (such as smoking and obesity), and mediating factors such as inflammatory response, endothelial dysfunction, and epidermal proliferation. 43 The list of established comorbidities with psoriasis is lengthy. 44 It includes myocardial infarction, 45 stroke, 46 cardiovascular mortality, 47–49 metabolic syndrome (obesity, insulin resistance, cholesterol abnormalities, hypertension, diabetes mellitus), 50,51 psoriatic arthritis, 52 mood disorders (notably anxiety, depression, and suicide), 53–55 Crohn's disease, 56–58 multiple sclerosis, 59 and T-cell lymphoma, 60 among other conditions. One of the most important comorbidities associated with psoriasis is the risk of cardiometabolic disorders. In patients with more severe psoriasis, the risk of cardiovascular disease is roughly the same as the risk conferred by diabetes. 45,46 Patients treated for severe psoriasis are 30 times more likely to experience a MACE attributable to psoriasis than to develop a melanoma. 47,61 Severe psoriasis is associated with approximately five years life lost compared to patients without psoriasis, mainly owing to cardiovascular disease, but also other disorders including infection and kidney disorders. 62 The risk appears to vary with psoriasis disease severity (Table 5). Using a retrospective review of medical records from 9,035 psoriasis patients (aged 25–64 years) and 90,350 age- and practice-matched patients without psoriasis, the psoriasis patients were grouped into those with mild (<3% of BSA affected), moderate (3–10% of BSA

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