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      Bimekizumab in the Treatment of Plaque Psoriasis: Focus on Patient Selection and Perspectives

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          Abstract

          Psoriasis is a chronic systemic inflammatory disease that significatively impairs patients’ quality of life. Biological treatments are highly effective and safe and have led to breakthroughs in the management of patients with moderate-to-severe psoriasis. However, therapeutic response can be unsatisfactory or lost with time, leading to discontinuation of treatment. Bimekizumab is a humanized monoclonal antibody that specifically inhibits both interleukin (IL)-17A and IL-17F. The efficacy and safety of bimekizumab in moderate-to-severe plaque psoriasis has been demonstrated in Phase 2 and Phase 3 clinical trials. Bimekizumab may offer some advantages over other biological treatments, making it especially indicated for certain patients. This narrative review aims to summarize the latest published evidence on the use of bimekizumab for the treatment of moderate-severe plaque psoriasis, focusing on patient selection and therapeutic perspectives. Bimekizumab has been shown to be more efficacious than adalimumab, secukinumab and ustekinumab in clinical trials, with high estimated probabilities of achieving complete (approximately 60%) or almost complete clearance (approximately 85%) of psoriasis at weeks 10–16, and a good safety profile. Response to bimekizumab is usually fast and maintained in the long term for both biologic-naive patients and those resistant to previous biologic treatments. The usual maintenance dose of 320 mg every 8 weeks makes bimekizumab especially convenient for non-compliant patients. Moreover, the efficacy and safety of bimekizumab have also been demonstrated in psoriasis affecting challenging-to-treat areas, psoriatic arthritis and hidradenitis suppurativa. In conclusion, dual inhibition of IL-17A and IL-17F with bimekizumab is a good therapeutic option for moderate-to-severe psoriasis.

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          Psoriasis

          Psoriasis is a common, chronic papulosquamous skin disease occurring worldwide, presenting at any age, and leading to a substantial burden for individuals and society. It is associated with several important medical conditions, including depression, psoriatic arthritis, and cardiometabolic syndrome. Its most common form, chronic plaque or psoriasis vulgaris, is a consequence of genetic susceptibility, particularly in the presence of the HLA-C*06:02 risk allele, and of environmental triggers such as streptococcal infection, stress, smoking, obesity, and alcohol consumption. There are several phenotypes and research has separated pustular from chronic plaque forms. Immunological and genetic studies have identified IL-17 and IL-23 as key drivers of psoriasis pathogenesis. Immune targeting of these cytokines and of TNFα by biological therapies has revolutionised the care of severe chronic plaque disease. Psoriasis cannot currently be cured, but management should aim to minimise physical and psychological harm by treating patients early in the disease process, identifying and preventing associated multimorbidity, instilling lifestyle modifications, and employing a personalised approach to treatment.
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            IL-23 drives a pathogenic T cell population that induces autoimmune inflammation

            Interleukin (IL)-23 is a heterodimeric cytokine composed of a unique p19 subunit, and a common p40 subunit shared with IL-12. IL-12 is important for the development of T helper (Th)1 cells that are essential for host defense and tumor suppression. In contrast, IL-23 does not promote the development of interferon-γ–producing Th1 cells, but is one of the essential factors required for the expansion of a pathogenic CD4+ T cell population, which is characterized by the production of IL-17, IL-17F, IL-6, and tumor necrosis factor. Gene expression analysis of IL-23–driven autoreactive T cells identified a unique expression pattern of proinflammatory cytokines and other novel factors, distinguishing them from IL-12–driven T cells. Using passive transfer studies, we confirm that these IL-23–dependent CD4+ T cells are highly pathogenic and essential for the establishment of organ-specific inflammation associated with central nervous system autoimmunity.
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              Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17.

              Interleukin (IL)-17 is a pro-inflammatory cytokine that is produced by activated T cells. Despite increasing evidence that high levels of IL-17 are associated with several chronic inflammatory diseases including rheumatoid arthritis, psoriasis, and multiple sclerosis, the regulation of its expression is not well characterized. We observe that IL-17 production is increased in response to the recently described cytokine IL-23. We present evidence that murine IL-23, which is produced by activated dendritic cells, acts on memory T cells, resulting in elevated IL-17 secretion. IL-23 also induced expression of the related cytokine IL-17F. IL-23 is a heterodimeric cytokine and shares a subunit, p40, with IL-12. In contrast to IL-23, IL-12 had only marginal effects on IL-17 production. These data suggest that during a secondary immune response, IL-23 can promote an activation state with features distinct from the well characterized Th1 and Th2 profiles.
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                Author and article information

                Journal
                Patient Prefer Adherence
                Patient Prefer Adherence
                ppa
                Patient preference and adherence
                Dove
                1177-889X
                30 June 2023
                2023
                : 17
                : 1541-1549
                Affiliations
                [1 ]Department of Dermatology, Hospital de la Santa Creu i Sant Pau , Barcelona, Spain
                Author notes
                Correspondence: Gemma Camiña-Conforto, Department of Dermatology, Hospital de la Santa Creu i Sant Pau , Mas Casanovas 90, Bloque A, 5a planta (secretaria Dermatología), Barcelona, 08041, Spain, Tel +34 93 553 7007, Fax +34 93 553 7008, Email gcamina@santpau.cat
                Author information
                http://orcid.org/0000-0001-6083-0952
                Article
                350760
                10.2147/PPA.S350760
                10319282
                d54cf668-37ca-4628-b255-c7013e8302ba
                © 2023 Camiña-Conforto et al.

                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
                : 03 April 2023
                : 24 June 2023
                Page count
                Figures: 1, Tables: 1, References: 55, Pages: 9
                Categories
                Review

                Medicine
                psoriasis,bimekizumab,patient selection,interleukin-17,patient compliance,biological therapy
                Medicine
                psoriasis, bimekizumab, patient selection, interleukin-17, patient compliance, biological therapy

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