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      Call for Papers: Digital Platforms and Artificial Intelligence in Dementia

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      Efficacy and Safety of Secukinumab for the Treatment of Psoriasis: A Meta-Analysis of Pivotal Phase III Trials

      meta-analysis
      a , b , a , a , *
      Dermatology
      S. Karger AG
      Secukinumab, Etanercept, Adverse events, Psoriasis

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          Abstract

          Background: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. Objectives: Secukinumab, a fully humanized monoclonal antibody against IL-17A, was approved for the treatment of moderate-to-severe plaque psoriasis in the USA and European Union in 2015. The aim of this study was to systematically evaluate the efficacy and safety of secukinumab for the treatment of moderate and severe plaque psoriasis and provide an evidence-based reference for clinical practice. Methods: PubMed, Google Scholar, Cochrane Library, and Clinical Trials databases were searched. Pivotal phase III clinical trials were analysed. RevMan was used for the statistical analysis of the data. Results: Seven pivotal phase III clinical trials were analysed. All trials evaluated secukinumab in moderate-to-severe plaque psoriasis and had two common primary end points: the proportion of respondents to the Psoriasis Area and Severity Index (PASI) and the proportion of respondents to the Investigator’s Global Assessment (IGA). The total response ratios of PASI and IGA respondents in the secukinumab group were 82.8 and 71.3%, respectively, compared to placebo. Secukinumab was superior to etanercept, with risk ratios of 1.7 and 2.1, respectively. Secukinumab was generally well tolerated during the 1-year trial period. However, adverse events also occurred. Conclusion: Secukinumab was found to be more effective than etanercept and had an acceptable safety profile. Since psoriasis is an autoimmune disease that requires lifelong treatment, attention should be paid to its adverse effects.

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          Most cited references32

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          Psoriasis Pathogenesis and Treatment

          Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.
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            Global epidemiology of psoriasis: a systematic review of incidence and prevalence.

            The worldwide incidence and prevalence of psoriasis is poorly understood. To better understand this, we performed a systematic review of published population-based studies on the incidence and prevalence of psoriasis. Three electronic databases were searched from their inception dates to July 2011. A total of 385 papers were critically appraised; 53 studies reported on the prevalence and incidence of psoriasis in the general population. The prevalence in children ranged from 0% (Taiwan) to 2.1% (Italy), and in adults it varied from 0.91% (United States) to 8.5% (Norway). In children, the incidence estimate reported (United States) was 40.8/100,000 person-years. In adults, it varied from 78.9/100,000 person-years (United States) to 230/100,000 person-years (Italy). The data indicated that the occurrence of psoriasis varied according to age and geographic region, being more frequent in countries more distant from the equator. Prevalence estimates also varied in relation to demographic characteristics in that studies confined to adults reported higher estimates of psoriasis compared with those involving all age groups. Studies on the prevalence and incidence of psoriasis have contributed to a better understanding of the burden of the disease. However, further research is required to fill existing gaps in understanding the epidemiology of psoriasis and trends in incidence over time.
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              Secukinumab in plaque psoriasis--results of two phase 3 trials.

              Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points). The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept. Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).

                Author and article information

                Journal
                DRM
                Dermatology
                10.1159/issn.1018-8665
                Dermatology
                Dermatology
                S. Karger AG
                1018-8665
                1421-9832
                2024
                April 2024
                03 November 2023
                : 240
                : 2
                : 271-281
                Affiliations
                [a ]Department of Dermatology, Beijing Changping Hospital of Traditional Chinese Medicine, Beijing, China
                [b ]Department of Dermatology, Tongzhou Branch, Dongzhimen Hospital, Beijing University of Traditional Chinese Medicine, Beijing, China
                Author notes
                *Zhiyin Xie, misszhiyin0510@sina.com
                Article
                534703 Dermatology 2024;240:271–281
                10.1159/000534703
                37926074
                0980d32e-2f6b-47dd-aa49-6f8e9d89a594
                © 2023 S. Karger AG, Basel
                History
                : 05 July 2022
                : 29 September 2023
                Page count
                Figures: 5, Tables: 3, Pages: 11
                Funding
                The research was supported by the Beijing Traditional Chinese Medicine Science and Technology Project.
                Categories
                Skin Infections – Research Article

                Medicine
                Secukinumab,Etanercept,Adverse events,Psoriasis
                Medicine
                Secukinumab, Etanercept, Adverse events, Psoriasis

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