Beyond the TNF-α Inhibitors: New and Emerging Targeted Therapies for Patients with Axial Spondyloarthritis and their Relation to Pathophysiology

Drugs
Susanne Juhl Pedersen, Walter P Maksymowych

Abstract

Axial spondyloarthritis (axSpA) is a complex disease that affects the joints and entheses of axial and peripheral joints, and is associated with inflammation in extra-articular sites such as the gut. Improved knowledge on genetics and immunology has improved treatment options with the availability of treatments targeting tumor necrosis factor-α (TNF-α) and interleukin (IL)-17. However, these agents do not provide clinical benefit for about 40% of patients, and additional therapeutic options are necessary. Theories on pathogenesis includes misfolding of HLA-B*27 during its assembly leading to endoplasmic reticulum stress and autophagy/unfolded protein response (UPR). HLA-B*27 may express free heavy chain on the cell surface, which activates innate immune receptors on T, natural killer, and myeloid cells with pro-inflammatory effects. Activation of UPR genes is associated with increased TNF-α, interleukin-23 (IL-23), IL-17, interferon-γ expression, and expansion of T helper (Th)-17 cells. Certain genotypes of endoplasmic reticulum aminopeptidase (ERAP) 1 and 2 are associated with ankylosing spondylitis (AS) and functionally interact with the HLA-B27 peptidome. Innate immune cells type 3, which express RORγt, regulate expression o...Continue Reading

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Citations

Apr 9, 2019·Expert Opinion on Biological Therapy·Murat Torgutalp, Denis Poddubnyy
Dec 31, 2020·International Journal of Inflammation·Janisleya Silva Ferreira NevesAna Maria Sell
Mar 9, 2021·Frontiers in Immunology·Elena GianchecchiAlessandra Fierabracci
Jul 3, 2021·Journal of Personalized Medicine·Janisleya Silva Ferreira NevesAna Maria Sell

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