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      Emerging Oral Therapies for the Treatment of Psoriasis: A Review of Pipeline Agents

      , ,
      Pharmaceutics
      MDPI AG

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          Abstract

          The introduction of biologic agents for the treatment of psoriasis has revolutionized the current treatment landscape, targeting cytokines in the interleukin (IL)-23/IL-17 pathway and demonstrating strong efficacy and safety profiles in clinical trials. These agents however are costly, are associated with a risk of immunogenicity, and require administration by intravenous or subcutaneous injection, limiting their use among patients. Oral therapies, specifically small molecule and microbiome therapeutics, have the potential to be more convenient and cost-effective agents for patients and have been a focus of development in recent years, with few targeted oral medications available for the disease. In this manuscript, we review pipeline oral therapies for psoriasis identified through a search of ClinicalTrials.gov (30 June 2022–1 October 2023). Available preclinical and clinical trial data on each therapeutic agent are discussed. Small molecules under development include tumor necrosis factor inhibitors, IL-23 inhibitors, IL-17 inhibitors, phosphodiesterase-4 inhibitors, Janus kinase inhibitors, A3 adenosine receptor agonists, and sphingosine-1-phosphate receptor 1 agonists, several of which are entering phase III trials. Oral microbials have also demonstrated success in early phase studies. As new oral therapies emerge for the treatment of psoriasis, real-world data and comparative trials are needed to better inform their use among patients.

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          Psoriasis.

          Psoriasis is an immune-mediated, genetic disease manifesting in the skin or joints or both. A diverse team of clinicians with a range of expertise is often needed to treat the disease. Psoriasis provides many challenges including high prevalence, chronicity, disfiguration, disability, and associated comorbidity. Understanding the role of immune function in psoriasis and the interplay between the innate and adaptive immune system has helped to manage this complex disease, which affects patients far beyond the skin. In this Seminar, we highlight the clinical diversity of psoriasis and associated comorbid diseases. We describe recent developments in psoriasis epidemiology, pathogenesis, and genetics to better understand present trends in psoriasis management. Our key objective is to raise awareness of the complexity of this multifaceted disease, the potential of state-of-the-art therapeutic approaches, and the need for early diagnosis and comprehensive management of patients with psoriasis.
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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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              The IL-17 Family of Cytokines in Health and Disease

              The interleukin 17 (IL-17) family of cytokines contains 6 structurally related cytokines, IL-17A through IL-17F. IL-17A, the prototypical member of this family, just passed the 25 th anniversary of its discovery. While less is known about IL-17B-F, IL-17A (commonly known as IL-17) has received much attention for its pro-inflammatory role in autoimmune disease. Over the past decade, however, it has become clear that the functions of IL-17 are far more nuanced than simply turning on inflammation. Accumulating evidence indicates that IL-17 has important context- and tissue-dependent roles in maintaining health during response to injury, physiological stress and infection. Here, we discuss the functions of the IL-17 family, with a focus on the balance between the pathogenic and protective roles of IL-17 in cancer and autoimmune disease, including results of therapeutic blockade and novel aspects of IL-17 signal transduction regulation. The IL-17 cytokine family is relatively poorly understood, apart from the prototypical, founding member, IL-17A, which has achieved notoriety for its role in autoimmunity. In this review, McGeachy, Cua and Gaffen discuss the pathogenic and protective roles of the IL-17 family in health, inflammation, injury, microbial regulation and cancer.
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                Author and article information

                Contributors
                Journal
                PHARK5
                Pharmaceutics
                Pharmaceutics
                MDPI AG
                1999-4923
                January 2024
                January 15 2024
                : 16
                : 1
                : 111
                Article
                10.3390/pharmaceutics16010111
                38258121
                4c2c013d-b640-4df5-8327-ef1b1d9ecc73
                © 2024

                https://creativecommons.org/licenses/by/4.0/

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