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      Effectiveness of Brodalumab in Patients with Moderate-to-Severe Plaque Psoriasis Located in Difficult-to-Treat Areas

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          Abstract

          Background

          Recent knowledge of psoriasis pathogenesis has led to the development of selective drugs. Among these, brodalumab is a monoclonal antibody targeting the interleukin (IL)-17A receptor approved for the treatment of moderate-to-severe plaque psoriasis. Biologics may be considered in patients with milder diseases in case of active psoriatic arthritis, severe impact on patient’s quality of life, and involvement of sensitive and difficult-to-treat areas. These skin locations commonly require systemic drugs. Recently, psoriasis severity monitoring has also changed. Indeed, the clinical evaluation by means of specific efficacy scores was combined with serological evaluation by means of the assay of specific inflammatory biomarkers.

          Methods

          An observational study enrolled patients affected by moderate-to-severe plaque psoriasis involving difficult-to-treat areas, undergoing treatment with brodalumab to evaluate the effectiveness and safety of brodalumab in patients with psoriasis affecting difficult-to-treat areas (scalp and palmoplantar regions). Secondary outcomes were the assessment of the development of serum markers of inflammation during the treatment period as well as the evaluation of the dermoscopic features of the affected sites to quantify disease activity and response to treatment.

          Results

          Twenty-five patients were included in the study. A statistically significant reduction from baseline in PASI, PSSI, ppPASI and DLQI values as early as week 24 was observed, with further improvement up to week 52. Plasma levels of MMP-3, VEGF-A, and hs-PCR decreased during treatment from week 0 to week 52.

          Conclusion

          Our real-life experience suggests brodalumab as a valuable option for the management of psoriasis located in difficult-to-treat areas. Moreover, our study highlights that the use of brodalumab reduces the plasmatic levels of inflammatory biomarkers (MMP-3, VEGF-A and hs-PCR), showing how the drug modulates the skin inflammatory response by reducing systemic inflammation.

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          Most cited references45

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          Pathophysiology, Clinical Presentation, and Treatment of Psoriasis: A Review

          Approximately 125 million people worldwide have psoriasis. Patients with psoriasis experience substantial morbidity and increased rates of inflammatory arthritis, cardiometabolic diseases, and mental health disorders.
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            Pathogenesis and clinical features of psoriasis.

            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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              The Immunologic Role of IL-17 in Psoriasis and Psoriatic Arthritis Pathogenesis

              Psoriasis is a chronic, immune-mediated, inflammatory disease that is pathogenically driven by proinflammatory cytokines. This article reviews the immunologic role of interleukin (IL)-17, the major effector cytokine in the pathogenesis of psoriatic disease, along with the rationale for targeting the IL-17 cytokine family (IL-17A, IL-17F, and IL-17 receptor A) in the treatment of psoriasis and psoriatic arthritis. Emerging evidence indicates that major sources of IL-17A in patients with psoriatic disease are mast cells, γδ T cells, αβ T cells, and innate lymphoid cells in lesional skin and synovial fluid. Within the skin and joints, IL-17A acts on cellular targets, including keratinocytes, neutrophils, endothelial cells, fibroblasts, osteoclasts, chondrocytes, and osteoblasts, to stimulate production of various antimicrobial peptides, chemokines, and proinflammatory and proliferative cytokines, which, in turn, promote tissue inflammation and bone remodeling. The critical importance of the IL-23/IL-17A axis to the pathogenesis of psoriatic disease has resulted in many new biologic treatments targeting these cytokines. These biologics dramatically improve skin and joint symptoms in patients with moderate-to-severe psoriasis and psoriatic arthritis.
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                Author and article information

                Journal
                Clin Cosmet Investig Dermatol
                Clin Cosmet Investig Dermatol
                ccid
                Clinical, Cosmetic and Investigational Dermatology
                Dove
                1178-7015
                25 September 2023
                2023
                : 16
                : 2637-2644
                Affiliations
                [1 ]Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II , Naples, Italy
                Author notes
                Correspondence: Angelo Ruggiero, Section of Dermatology - Department of Clinical Medicine and Surgery, University of Naples Federico II , Via Pansini 5, Napoli, 80131, Italy, Tel +39 - 081 – 7462457, Fax +39 - 081 – 7462442, Email angeloruggiero1993@libero.it
                [*]

                These authors contributed equally to this work

                [†]

                Professor Gabriella Fabbrocini passed away on 3rd March 2023

                Author information
                http://orcid.org/0000-0001-5940-0592
                http://orcid.org/0000-0002-4658-7391
                Article
                423234
                10.2147/CCID.S423234
                10541085
                37780688
                e1be6cc3-66a1-4ea3-a233-09a0e2651ab6
                © 2023 Cacciapuoti 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
                : 20 June 2023
                : 20 September 2023
                Page count
                Figures: 3, References: 45, Pages: 8
                Categories
                Original Research

                Dermatology
                brodalumab,psoriasis,difficult-to-treat areas,biologic drugs,efficacy
                Dermatology
                brodalumab, psoriasis, difficult-to-treat areas, biologic drugs, efficacy

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