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      Enhancing the Response Rate to Recombinant Uricases in Patients with Gout

      research-article
      Author(s): 1 , 2 , 2 ,
      Publication date (Electronic):
      Journal: Biodrugs
      Publisher: Springer International Publishing

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          Abstract

          Refractory, or uncontrolled, gout is a chronic, progressive, inflammatory arthropathy resulting from continued urate deposition after failed attempts to lower serum uric acid below the therapeutic threshold with oral urate-lowering therapies such as allopurinol and febuxostat. Recombinant uricase is increasingly being used to treat refractory gout; however, the immunogenicity of uricase-based therapies has limited the use of these biologic therapies. Antidrug antibodies against biologic therapies, including uricase and PEGylated uricase, can lead to loss of urate-lowering response, increased risk of infusion reactions, and subsequent treatment failure. However, co-therapy with an immunomodulator can attenuate antidrug antibody development, potentially increasing the likelihood of sustained urate lowering, therapy course completion, and successful treatment outcomes. This review summarizes evidence surrounding the use of immunomodulation as co-therapy with recombinant uricases.

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          Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis

          Yen-Ju Lin, Martina Anzaghe, Stefan Schülke (2020)
          Rheumatoid arthritis (RA) is an autoimmune disease that involves multiple joints bilaterally. It is characterized by an inflammation of the tendon (tenosynovitis) resulting in both cartilage destruction and bone erosion. While until the 1990s RA frequently resulted in disability, inability to work, and increased mortality, newer treatment options have made RA a manageable disease. Here, great progress has been made in the development of disease-modifying anti-rheumatic drugs (DMARDs) which target inflammation and thereby prevent further joint damage. The available DMARDs are subdivided into (1) conventional synthetic DMARDs (methotrexate, hydrochloroquine, and sulfadiazine), (2) targeted synthetic DMARDs (pan-JAK- and JAK1/2-inhibitors), and (3) biologic DMARDs (tumor necrosis factor (TNF)-α inhibitors, TNF-receptor (R) inhibitors, IL-6 inhibitors, IL-6R inhibitors, B cell depleting antibodies, and inhibitors of co-stimulatory molecules). While DMARDs have repeatedly demonstrated the potential to greatly improve disease symptoms and prevent disease progression in RA patients, they are associated with considerable side-effects and high financial costs. This review summarizes our current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.
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            2020 American College of Rheumatology Guideline for the Management of Gout

            John FitzGerald, Nicola Dalbeth, Ted Mikuls … (2020)
            To provide guidance for the management of gout, including indications for and optimal use of urate-lowering therapy (ULT), treatment of gout flares, and lifestyle and other medication recommendations.
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              How tolerogenic dendritic cells induce regulatory T cells.

              Roberto Maldonado, Ulrich H. von Andrian (2010)
              Since their discovery by Steinman and Cohn in 1973, dendritic cells (DCs) have become increasingly recognized for their crucial role as regulators of innate and adaptive immunity. DCs are exquisitely adept at acquiring, processing, and presenting antigens to T cells. They also adjust the context (and hence the outcome) of antigen presentation in response to a plethora of environmental inputs that signal the occurrence of pathogens or tissue damage. Such signals generally boost DC maturation, which promotes their migration from peripheral tissues into and within secondary lymphoid organs and their capacity to induce and regulate effector T cell responses. Conversely, more recent observations indicate that DCs are also crucial to ensure immunological peace. Indeed, DCs constantly present innocuous self- and nonself-antigens in a fashion that promotes tolerance, at least in part, through the control of regulatory T cells (Tregs). Tregs are specialized T cells that exert their immunosuppressive function through a variety of mechanisms affecting both DCs and effector cells. Here, we review recent advances in our understanding of the relationship between tolerogenic DCs and Tregs. Copyright © 2010 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Brian LaMoreaux:
                ORCID: http://orcid.org/0000-0001-7521-241X
                BLaMoreaux@horizontherapeutics.com
                Journal
                Journal ID (nlm-ta): BioDrugs
                Journal ID (iso-abbrev): BioDrugs
                Title: Biodrugs
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 1173-8804
                ISSN (Electronic): 1179-190X
                Publication date (Electronic): 22 March 2022
                Publication date PMC-release: 22 March 2022
                Pages: 1-9
                Affiliations
                [1 ]GRID grid.430387.b, ISNI 0000 0004 1936 8796, Department of Medicine, , Rutgers Robert Wood Johnson Medical School, ; New Brunswick, NJ USA
                [2 ]GRID grid.476366.6, ISNI 0000 0004 4903 3495, Medical Affairs, , Horizon Therapeutics, ; 1 Horizon Way, Deerfield, IL 60015 USA
                Author information
                http://orcid.org/0000-0002-1558-1202
                http://orcid.org/0000-0002-4199-4844
                http://orcid.org/0000-0001-7521-241X
                Article
                Publisher ID: 517
                DOI: 10.1007/s40259-022-00517-x
                PMC ID: 8938732
                PubMed ID: 35316517
                SO-VID: 74deeaae-8129-4a6d-a13d-54a0a59cd2ba
                Copyright © © The Author(s) 2022
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

                History
                Date accepted : 25 January 2022
                Funding
                Funded by: Horizon Therapeutics plc
                Categories
                Subject: Leading Article

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