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      Spotlight on brodalumab in the treatment of plaque psoriasis: the evidence to date

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          Abstract

          The IL-17/IL-23 axis is now understood to influence psoriasis, and the development of novel IL-17 inhibitor medications marks a sea change in the treatment of psoriasis. Brodalumab is a recombinant, fully human immunoglobulin IgG2 monoclonal antibody specifically targeted against IL-17RA. This article discusses the mechanism of action and the efficacy and safety profile of brodalumab presented in the literature. Brodalumab, the latest approved anti-IL-17-class medication, is the only one that exerts its effects on IL-17C as well as on IL-17A and IL-17F, blocking the shared IL-17 receptor A. In this sense, considering the recent evidence, brodalumab could have beneficial effects not only on psoriasis, but also on atopic dermatitis. It could also serve as a therapeutic alternative in patients who develop paradoxical eczematous reactions or atopic-like dermatitis during treatment with other anti-IL-17A (secukinumab, ixekizumab).

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          Pathogenesis and clinical features of psoriasis.

          Christopher EM Griffiths, Jonathan Barker (2007)
          Psoriasis, a papulosquamous skin disease, was originally thought of as a disorder primarily of epidermal keratinocytes, but is now recognised as one of the commonest immune-mediated disorders. Tumour necrosis factor alpha, dendritic cells, and T-cells all contribute substantially to its pathogenesis. In early-onset psoriasis (beginning before age 40 years), carriage of HLA-Cw6 and environmental triggers, such as beta-haemolytic streptococcal infections, are major determinants of disease expression. Moreover, at least nine chromosomal psoriasis susceptibility loci have been identified. Several clinical phenotypes of psoriasis are recognised, with chronic plaque (psoriasis vulgaris) accounting for 90% of cases. Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis. A more complete understanding of underlying pathomechanisms is leading to new treatments, which will be discussed in the second part of this Series.
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            Randomized, double-blind, placebo-controlled study of brodalumab, a human anti-IL-17 receptor monoclonal antibody, in moderate to severe asthma.

            William Busse, Stephen T. Holgate, Edward Kerwin … (2013)
            IL-17 signaling has been implicated in development and persistence of asthma. Cytokine-targeted strategies blocking IL-17 receptor signaling may be beneficial in asthma treatment.
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              The IL-17 Family of Cytokines in Psoriasis: IL-17A and Beyond

              Nicolò Brembilla, Luisa Senra, Wolf-Henning Boehncke (2018)
              Psoriasis is a frequent chronic inflammatory skin disease, nowadays considered a major global health problem. Several new drugs, targeting the IL-23/IL-17A pathway, have been recently licensed or are in clinical development. These therapies represent a major improvement of the way in which psoriasis is managed, since they show an unprecedented efficacy on skin symptoms of psoriasis. This has been made possible, thanks to an increasingly more accurate pathogenic view of psoriasis. Today, the belief that Th17 cells mediate psoriasis is moving to the concept of psoriasis as an IL-17A-driven disease. New questions arise at the horizon, given that IL-17A is part of a newly described family of cytokines, which has five distinct homologous: IL-17B, IL-17C, IL-17D, IL-17E, also known as IL-25 and IL-17F. IL-17 family cytokines elicit similar effects in target cells, but simultaneously trigger different and sometimes opposite functions in a tissue-specific manner. This is complicated by the fact that IL-17 cytokines show a high capacity of synergisms with other inflammatory stimuli. In this review, we will summarize the current knowledge around the cytokines belonging to the IL-17 family in relation to skin inflammation in general and psoriasis in particular, and discuss possible clinical implications. A comprehensive understanding of the different roles played by the IL-17 cytokines is crucial to appreciate current and developing therapies and to allow an effective pathogenesis- and mechanisms-driven drug design.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Clin Cosmet Investig Dermatol
                Journal ID (iso-abbrev): Clin Cosmet Investig Dermatol
                Journal ID (publisher-id): CCID
                Journal ID (pmc): ccid
                Title: Clinical, Cosmetic and Investigational Dermatology
                Publisher: Dove
                ISSN (Electronic): 1178-7015
                Publication date (Electronic): 01 May 2019
                Publication date Collection: 2019
                Volume: 12
                Pages: 311-321
                Affiliations
                [1 ]Dermatology, Department of “Medicina dei Sistemi”, University of Rome Tor Vergata , Rome, Italy
                Author notes
                Correspondence: M GalluzzoDermatology, Department of “Medicina dei Sistemi”, University of Rome Tor Vergata , Viale Oxford, 81, Rome00133, ItalyTel +39 062 090 2743Fax +39 062 090 2742Email marco.galluzzo83@ 123456gmail.com
                [*]

                These authors contributed equally to this work

                Article
                Publisher ID: 165605
                DOI: 10.2147/CCID.S165605
                PMC ID: 6503649
                SO-VID: f0c2e40e-7cc4-479a-9474-38adf603f85e
                Copyright © © 2019 Galluzzo et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 23 October 2018
                Date accepted : 15 February 2019
                Page count
                Figures: 1, Tables: 2, References: 63, Pages: 11
                Categories
                Subject: Review

                ScienceOpen disciplines: Dermatology
                Keywords: psoriasis,biologics,anti-il17ra,brodalumab,pasi100,atopic dermatitis
                Data availability:
                ScienceOpen disciplines: Dermatology
                Keywords: psoriasis, biologics, anti-il17ra, brodalumab, pasi100, atopic dermatitis

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