INTRODUCTION
Psoriasis is a chronic, immune-mediated, inflammatory skin disease characterized by erythematous and scaly plaques. The prevalence of psoriasis varies across the globe, with estimates ranging from 0.09% to 5.1% depending on the country.1 Roughly 3% of the United States population is affected, and approximately 20-30% of those patients suffer from moderate-to-severe disease, which requires more intensive treatments than topical therapies.2-4The perception of psoriasis as a disease entity has evolved over time. Initially considered to be a solely cutaneous disorder, psoriasis is now recognized as a systemic condition, with associated cardiovascular complications, inflammatory arthritis, and depression.5,6 Poorer quality of life, specifically measured in terms of emotional health and the impact on relationships, is well documented in patients suffering from psoriasis.7-10The development of targeted biologics has improved the treatment outlook of affected patients. The psoriasis area and severity index (PASI) is a commonly used tool to calculate the extent and severity of cutaneous psoriasis. Changes in PASI are the key measure by which the efficacy of therapies is assessed. A 75% improvement in PASI score has long been the established endpoint for determining treatment outcomes. As research into the pathogenesis of psoriasis has progressed, increasingly specific mediators and targeted biologics have been discovered. The success of this translational research has elevated the goals for clearing psoriasis lesions, with the PASI-90 response rate emerging as a new standard.11Interleukin (IL)-17 is now recognized as a fundamental component in the pathogenesis of psoriasis. Produced by mast cells, neutrophils, and T cells, IL-17 causes inflammation through the proliferation and activation of keratinocytes, fibroblasts, and dendritic cells.12 IL-17-producing γδ T cells have found to be significantly increased in psoriasis plaques.13 Based on these observations, several medications directed against IL-17 have recently been developed.Secukinumab (Novartis Pharma AG, Basel, Switzerland) is a fully human IgG1K monoclonal antibody that selectively neutralizes IL-17A. Secukinumab has demonstrated utility in the treatment of moderate-to-severe plaque psoriasis and has exhibited superior efficacy over anti-TNF and anti-IL12/23 therapies.14-19 Histologically, biopsies taken from patients treated with secukinumab show decreased epidermal hyperplasia and decreased expression of IL-17A.20 In this article, we review the safety and efficacy data of secukinumab from recent, large-scale clinical trials.Treatment of Plaque PsoriasisThe CLEAR trial (ClinicalTrials.gov/NCT02074982) was performed to compare the long-term safety and efficacy of secukinumab and ustekinumab.21 This double-blinded phase IIIb study randomized 676 patients to treatment with either secukinumab 300 mg or ustekinumab (45 mg for weight ≤100 kg and 90 mg for >100 kg). The primary objective of PASI-90 at week 16 was achieved, and the efficacy was significantly higher and sustained over 52 weeks for secukinumab versus ustekinumab (76% versus 61%; P less than .0001) In addition, higher PASI-100 responses were seen with secukinumab (46% versus 36%; P = .0103). Patient-reported measures of pain, itching, and scaling also favored secukinumab. The frequency of adverse events or serious adverse events did not vary significantly between groups. The most common adverse events were nasopharyngitis, upper respiratory tract infection, and headache (consistent with those observed in previous clinical trials).Different maintenance dosing schedules for secukinumab were examined in the phase III SCULPTURE trial (ClinicalTrials.gov/NCT01406938).22 The SCULTPURE study measured the degree to which positive responses to secukinumab are maintained using either a dosing regimen of retreatment as needed (RAN) or the standard fixed-interval (FI) dosing every four weeks. In the RAN study arm, secukinumab 300 mg was administered only after a loss of 20% or more of maximum PASI score improvement versus baseline, plus a loss of PASI-75 response. Comparing results from the two treatment arms showed that at week 52, FI dosing maintained PASI-75 responses more effectively than RAN, highlighting the importance of regular and sustained secukinumab administration.The SCULPTURE trial underwent a 3-year extension period, during which patients from the core study received the same double-blinded maintenance treatment of either four-week FI or RAN dosing.23 Over this long-term period, the FI regimen
