Journal of Clinical and Aesthetic Dermatology

Plaque-type Psoriasis Supplement 2016

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

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A Novel Paradigm for Treatment of Moderate-to-severe Plaque-type Psoriasis [JUNE 2016 • VOLUME 9 • NUMBER 6 • SUPPLEMENT 1] SUPPLEMENT TO THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY S7 Secukinumab Review of Clinical Evidence from the Pivotal Studies ERASURE, FIXTURE, and CLEAR a April W. Armstrong, MD; b Kim Papp, MD; c Leon Kircik, MD a University of Southern California, Los Angeles, California; b Probity Medical Research, Waterloo, Ontario, Canada; c Icahn School of Medicine at Mount Sinai, New York, New York Introduction Psoriasis is a chronic, inflammatory skin disease that affects 3.2 percent of the United States population and approximately 125 million individuals worldwide. 1 Translational studies have shown that interleukin (IL)-17A, a pro-inflammatory cytokine, plays a crucial role in the pathogenesis of psoriasis. 2–5 Secukinumab is a fully human, anti-interleukin-17A (IL-17A) monoclonal antibody that binds and neutralizes IL-17A. The action of secukinumab leads to a decrease in IL-17A levels, dermal inflammatory infiltrate, and epidermal thickening. Clinically, psoriasis patients who have been treated with secukinumab experience significant improvement in their psoriasis disease severity, itching, and quality of life. 6 –9 Approved Dosing Clinical trial results have led to the approval of secukinumab for plaque psoriasis in the United States and parts of Europe and Asia in 2015. For example, in the United States, the approved dosing for secukinumab for plaque psoriasis is 300mg subcutaneously every week for the first five weeks and then 300mg subcutaneously every four weeks. As of February 2016, secukinumab has also gained United States Food and Drug Administration (FDA) approval for psoriatic arthritis and ankylosing spondylitis. In this article, the authors discuss the findings from the landmark, pivotal trials regarding secukinumab in the treatment of plaque psoriasis: ERASURE (secukinumab vs. placebo), FIXTURE (secukinumab vs. etanercept vs. placebo), and CLEAR (secukinumab vs. ustekinumb). This discussion serves to improve practitioners' understanding of the clinical trial evidence for secukinumab in psoriasis. Clinical Evidence In 2014, Langley et al 6 published the landmark paper in The New England Journal of Medicine that introduced IL- 17 inhibitors as a key, novel treatment option for plaque psoriasis. In this article, the investigators evaluated the efficacy and safety of secukinumab for moderate-to-severe psoriasis in two Phase 3 studies. The ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) study evaluated the efficacy of secukinumab versus placebo. In comparison, the FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) study evaluated the efficacy of secukinumab versus etanercept and versus placebo. Secukinumab versus Placebo: the ERASURE study Primary objective. In the 52-week ERASURE study, the primary objective was to evaluate Week 12 superiority of secukinumab over placebo as measured by two coprimary endpoints: 1) proportion of patients experiencing 75 percent or more reduction in psoriasis severity from baseline using the Psoriasis Area and Severity Index (PASI) score (or proportion of patients achieving PASI 75), and 2) proportion of patients achieving 0 (clear) or 1 (almost clear) on a 5-point modified Investigator's Global Assessment (IGA) (scores 0–4). Study design and study population. The ERASURE study is a randomized, Phase 3, double-blind, 52-week clinical trial that took place between June 2011 through April 2013 at 88 sites worldwide. This study had a screening period of 1 to 4 weeks, an induction period of 12 weeks, a maintenance period of 40 weeks, and a follow-up period of eight weeks. The inclusion criteria for the study are as follows. To be eligible for the study, the patients had to be 18 years or older with moderate-to-severe plaque psoriasis that had been diagnosed at least six months before randomization. In addition, their plaque psoriasis had to be poorly controlled with topical treatments, phototherapy, systemic therapy, or a combination of these treatments. Patients had to have a baseline PASI score of 12 or higher, a score of 3 or 4 on the modified IGA, and body surface area (BSA) of 10 percent or

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