Secukinumab: A Review of Safety and Efficacy in Psoriatic Arthritis
August 2017 | Volume 16 | Issue 8 | Supplement | s118 | Copyright © 2017
Peter W. Hashim MD MHS,a Kim A. Papp MD PHD,b Philip J. Mease MDc
aThe Icahn School of Medicine at Mount Sinai, Department of Dermatology, New York, NY bK. Papp Clinical Research and Probity Medical Research, Waterloo, Ontario, Canada cSwedish Hospital Clinical Research Division, Swedish Medical Center, and University of Washington School of Medicine, Seattle, WA
No abstract available
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Psoriatic arthritis (PsA) is an immune-mediated, inflammatory disease of the peripheral joints, axial spine, and entheses. The frequency of PsA among patients with psoriasis has been estimated at up to 30%, corresponding to a prevalence of up to 1% in the general population in the United States and Europe, with lower numbers seen in other parts of the world based on genetic differences (eg, less commonly among Asian and African populations.)1-3 Patients experience significant functional disability and suffer from poorer quality-of-life measures than patients with cutaneous psoriasis alone.4-5Interleukin (IL)-17A has been identified as an important component of PsA pathophysiology.6 Released by T helper 17 cells, IL-17 affects a number of cells to promote an inflammatory response. Interactions with macrophages and dendritic cells cause elevations in keratinocyte proliferation and the proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor (TNF); those with endothelial cells yield thrombosis and tissue destruction; those with fibroblasts and chondrocytes cause cartilage destruction; those with osteoblasts lead to the production of RANK ligand, osteoclastogenesis, and bone erosion.7-9 Through the upregulation of proteases, IL-17 induces the breakdown of cartilage matrices and inhibits their synthesis.10 In PsA, affected joints have been shown to contain higher levels of IL-17+ T cells, a finding that correlates with disease activity and radiographic erosion.11 Using the inhibition of IL-17, new biologic therapies offer a means to improve the signs and symptoms of PsA.Secukinumab (Novartis Pharma AG, Basel, Switzerland) is an IgG1K monoclonal antibody that selectively blocks IL-17A.12 Initially approved for moderate-to-severe plaque psoriasis, secukinumab gained approval for PsA in Europe in October 2015 and in the United States in January 2016.Prior to secukinumab, the treatment for severe PsA centered on biologic disease-modifying antirheumatic drugs such as anti-TNF agents and ustekinumab. Although anti-TNF medications have greatly improved the therapy paradigm for PsA, additional agents are needed in order to provide options for non-responders, patients who lose response, or those who experience adverse events.The safety and efficacy of secukinumab in the treatment of PsA have been evaluated in the FUTURE-1 and FUTURE-2 phase III clinical trials. Over 1000 patients were enrolled in these studies, comparing different dosing regimens of secukinumab to placebo. In this review, we examine the principal results from these important trials.FUTURE-1 Clinical TrialFUTURE-1 (ClinicalTrials.gov/NCT01392326) is a phase III study of 606 patients with active PsA.13 Patients were initially randomized to treatment with either secukinumab 150 mg, secukinumab 75 mg, or placebo. Both treatment groups received intravenous secukinumab (10 mg/kg) at weeks 0, 2, and 4. After the first 4 weeks, patients received subcutaneous secukinumab at either 75 mg or 150 mg every 4 weeks. After 16 weeks, placebo responders (defined as those achieving a 20% reduction in tender and swollen joint counts) continued to receive placebo until week 24, whereas placebo non-responders were re-randomized to receive 150 mg or 75 mg of secukinumab. The primary endpoint was the American College of Rheumatology 20 (ACR20) response, which denotes ≥ 20% improvement in joint symptoms. These rates were examined at week 24 in patients treated with either secukinumab 150 mg, secukinumab 75 mg, or placebo.At week 24, patients in the 150 mg group and 75 mg group showed significantly higher ACR20 responses (50.0% and 50.5%, respectively) compared to placebo (17.3%; P less than .001 for both secukinumab comparisons). Additional clinical domains that displayed significant improvement were enthesitis, dactylitis, skin and nail disease, physical function, and quality of life. Overall, secukinumab was well tolerated, although patients did experience a modestly higher rate of candidiasis (1% with secukinumab versus 0% with placebo)—a predictable side effect given that IL-17 is involved in host defense against candida infection.Van der Heijde et al.14 reviewed the inhibition of radiographic progression of joint disease in FUTURE-1 patients. The