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Novel therapies for immune-mediated inflammatory diseases: What can we learn from their use in rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, psoriasis, Crohn's disease and ulcerative colitis?
  1. Kenneth F Baker1,2,
  2. John D Isaacs1,2
  1. 1Musculoskeletal Research Group and Arthritis Research UK Centre of Excellence in Rheumatoid Arthritis Pathogenesis, Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
  2. 2Newcastle NIHR Biomedical Research Centre, Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University, Newcastle upon Tyne, UK
  1. Correspondence to Professor John D Isaacs, Musculoskeletal Research Group, Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, William Leech Building, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK; john.isaacs{at}ncl.ac.uk

Abstract

The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.

In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.

  • autoimmune diseases
  • autoimmunity
  • DMARDs
  • treatment

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Footnotes

  • Handling editor Tore K Kvien

  • Contributors Conception: JDI. Design, analysis, drafting and final approval of the manuscript: JDI, KFB.

  • Funding KFB is supported by a Wellcome Trust Fellowship in Translational Medicine and Therapeutics (102595/Z/13/A) and a grant from the National Institute for Health Research Newcastle Biomedical Research Centre (BH136167/PD0045) based at Newcastle Hospitals NHS Foundation Trust and Newcastle University. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

  • Competing interests JDI has received honoraria, research grants or consulting fees from AbbVie; Biogen; Bristol-Myers-Squibb Company; Celltrion Healthcare; Chugai Pharmaceutical; Eli Lilly and Company; Hospira; Janssen Pharmaceuticals; Merck Serono S A; Pfizer; and Roche Laboratories. KFB has no competing interests to declare.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Data sharing statement None declared.

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