Bedside to bench: defining the immunopathogenesis of psoriatic arthritis

Abstract

Psoriatic arthritis (PsA) is an immune-mediated, systemic inflammatory disorder. PsA can present with heterogeneous clinical features. Advances in understanding the immunopathogenesis of PsA have helped to facilitate the development of agents targeting specific components of the dysregulated inflammatory and immune responses relevant to PsA. Interestingly, agents with distinct mechanisms of action have shown differential responses across the various disease domains of PsA, counter to what might have been expected from basic science investigations. Here, we review data utilizing various novel targeted therapies for PsA, focusing on biologic and targeted synthetic therapies. These data might support the idea of a ‘bedside to bench’ concept, whereby results from clinical trials of specific targeted therapies inform our understanding of the immunopathogenesis of PsA. For example, TNF inhibition confers substantial and comparable benefit for all domains of PsA, supporting the view that TNF is a central pro-inflammatory cytokine across diverse areas of disease involvement. On the other hand, inhibition of IL-12–IL-23, as compared with inhibition of TNF, has greater efficacy for psoriasis, comparable efficacy for peripheral arthritis, but was ineffective in studies of axial spondyloarthritis. Data from studies of agents with distinct mechanisms of action will help to further refine our understanding of the immunopathogenesis of PsA.

Key points

  • The development and introduction of novel targeted therapies has improved outcomes for patients with autoimmune systemic inflammatory diseases, including psoriatic arthritis (PsA).

  • Whereas some agents, such as TNF inhibitors, have been highly effective across many autoimmune diseases, and across domains of disease, other agents have had disparate impacts on various diseases and domains.

  • With a ‘bedside to bench’ approach to systemic autoimmune diseases, data from clinical trials targeting various immune mediators could further our understanding of the immunopathogenesis of PsA and other diseases.

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Fig. 1: Immunopathogenesis of PsA.
Fig. 2: Summary of immune target interactions in PsA.
Fig. 3: Summary of cytokine and non-cytokine targets in various chronic inflammatory diseases.
Fig. 4: Bedside to bench: towards precision medicine in PsA.

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Bravo, A., Kavanaugh, A. Bedside to bench: defining the immunopathogenesis of psoriatic arthritis. Nat Rev Rheumatol 15, 645–656 (2019). https://doi.org/10.1038/s41584-019-0285-8

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