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 7 pain associated with psoriasis. Responses are converted to numbers (0=not at all, 4=very severe) and the total score evaluated (best possible score is 0, worst possible score is 32). When the PSI was contrasted with the static Physician's Global Assessment (sPGA), which rates psoriasis in terms of clearance (0=clear of disease and 5=very severe disease), it helped to elucidate the patients' perception in terms of how an sPGA score of 0 (clear) and 1 (almost clear) might differ. From the vantage point of the clinical observer, sPGA 0 and 1 are very similar. Among patients with PSI of 0, 60.8 percent were sPGA 0 and only 5.3 percent were sPGA 1. This was a significant difference (p<0.001). Among patients who could be classified as a "PSI responder," defined as those with a PSI score ≤8 and no single item scoring ≤1 point), 94.9 percent were sPGA 0 and 54.3 percent sPGA 1 (p<0.001). This indicates that significantly more patients with complete skin clearance (sPGA 0) report no psoriasis symptoms severity compared to patients who are "almost clear" (sPGA). 16 In conclusion, PROs both complement and qualify objective ("observer only") assessments of psoriasis. In terms of understanding the patient's perspective on psoriasis, not all body areas are equal. Psoriasis in visible and socially important areas of the body (face and neck) is more distressing than psoriasis on the legs or the arms, which can be effectively hidden from most onlookers. Sex and age play an important role in terms of how patients respond to psoriasis. In terms of clearance, the more complete the clearance the better. While clinicians might be tempted to view "clear" and "almost clear" as similar outcomes, patients see them as significantly different endpoints. A variety of important new psoriasis- specific PROs have been and are being developed. These are important new tools that may help improve treatment of patients. Systemic Treatment of Psoriasis: What's New? This overview of the newest systemic treatments and advances in small molecules is presented by small molecules and then by drug targets. Small molecules. Apremilast. The LIBERATE study (Evaluation in a Placebo-Controlled Study of Oral Apremilast and Etanercept in Plaque Psoriasis) is a double-blind, double-dummy study that evaluated the safety and efficacy of apremilast or etanercept versus placebo in 250 biologic-naïve patients with moderate-to- severe psoriasis over a 16-week period. At Week 16, significantly more patients achieved PASI 75 with apremilast 30mg twice daily (39.8%) or etanercept 50mg once a week (48.2%) than placebo (11.9%), p<0.0001 for both active treatments. Although the study was not powered to compare apremilast to etanercept, a post- hoc analysis found results between these two active treatments were not significantly different. After 16 weeks, all patients were switched to apremilast 30mg twice daily, and efficacy in former etanercept patients could be maintained. No unexpected adverse events were observed. 17 A post-treatment observational follow- up phase to 104 weeks has not yet been reported. Weight is associated with psoriasis disease severity and may affect treatment outcomes. In a post-hoc analysis of the ESTEEM 1 study, it was found that in patients who took apremilast 30mg, the percentage change in body weight over baseline was not correlated with the percentage change in PASI score at Week 16 or Week 52. 18 Tofacitinib. Tofacitinib (CP-690,550) is a janus- kinase (JAK) inhibitor that primarily inhibits the JAK 1 and 3 pathways. Tofacitinib is approved therapy for treating rheumatoid arthritis and is known to decrease inflammatory cytokines, chemokines, and several types of inflammatory cells. Tofacitinib is also effective in treating psoriasis and is relatively well-tolerated. 1 9 PASI 75 results over time demonstrate tofacitinib is more effective than placebo and PASI 75 rates increase in dose-dependent fashion. A total of 1,106 adults with chronic plaque psoriasis were randomized in a 12-week, Phase 3 clinical study into four treatment groups: tofacitinib 5mg twice daily, tofacitinib 10mg twice daily, etanercept 50mg twice weekly, and placebo. This study found tofacitinib was non-inferior to etanercept with rates of adverse events similar across groups. 2 0 Tofacitinib is also used off-label in dermatology practices; among these currently reported off-label uses are the treatment of atopic nails, 21 severe atopic dermatitis, 22 and vitiligo. 23 Certolizumab-pegol. Certolizumab-pegol is a PEG- ylated anti-tumor necrosis factor alpha (TNFα) biologic approved for treatment of rheumatoid arthritis and Crohn's disease. In 2007, results from a Phase 2 clinical trial of certolizumab explored the role of this small molecule in the treatment of psoriasis. This study found PASI 75 results obtained by 75 and 83 percent of patients (based on dose) compared to seven percent placebo with PGA scores of clear or almost clear obtained by 53 and 72 percent (p<0.001 for both treatment doses versus placebo) with no unexpected adverse events. 24 A Phase 3 trial is currently underway evaluating two doses (400mg at Weeks 0, 2, 4 and then 200mg every two weeks starting at Week 6 for 48 weeks; 400mg every two weeks over 47 weeks) versus placebo. The primary endpoint of this study is PASI 75 at 16 weeks. Inclusion criteria for this study are PASI ≥12, BSA affected ≥10 percent, and PGA ≥3. Drug targets and new treatments. Cytokines and cytokine inhibitors occur across a spectrum ranging from very pro-inflammatory (TNFα, for example) to very anti- inflammatory (interleukin [IL]-4, IL-10, and others, for example). Drug targets may be IL-12 (ustekinumab), IL- 23 (ustekinumab, guselkumab, tildrakizumab, BI- 655066), and IL-17 (secukinumab, ixekizumab, brodalumab). Since IL-17 and IL-22 occur downstream in the cascade from IL-23, guselkumab, tildrakizumab, and

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