No Significant Effects of IL-23 on Initiating and Perpetuating the Axial Spondyloarthritis: The Reasons for the Failure of IL-23 Inhibitors.

Hua Zhang,Sheng-Ming Dai,Han-Lei Jiang

doi:10.3389/fimmu.2022.818413

Hua Zhang, Sheng-Ming Dai + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2022.818413

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Abstract

Axial spondyloarthritis (axSpA) is comprised of ankylosing spondylitis (AS) and non-radiographic axSpA. In recent years, the involvement of the interleukin (IL)-23/IL-17 axis in the pathophysiology of axSpA has been widely proposed. Since IL-23 is an upstream activating cytokine of IL-17, theoretically targeting IL-23 should be effective in axSpA, especially after the success of the treatment with IL-17 blockers in the disorder. Unfortunately, IL-23 blockade did not show meaningful efficacy in clinical trials of AS. In this review, we analyzed the possible causes of the failure of IL-23 blockers in AS: 1) the available data from an animal model is not able to support that IL-23 is involved in a preclinical rather than clinical phase of axSpA; 2) Th17 cells are not principal inflammatory cells in the pathogenesis of axSpA; 3) IL-17 may be produced independently of IL-23 in several immune cell types other than Th17 cells in axSpA; 4) no solid evidence supports IL-23 as a pathogenic factor to induce enthesitis and bone formation. Taken together, IL-23 is not a principal proinflammatory cytokine in the pathogenesis of axSpA.

Highlights

Axial spondyloarthritis comprised of ankylosing spondylitis (AS) and non-radiographic axSpA is an inflammatory disease of the axial skeleton
Therapies of AS have been limited to mainly physiotherapy and non-steroidal anti-inflammatory drugs (NSAIDs), while conventional immunosuppressants or disease-modifying anti-rheumatic drugs may only be helpful in concurrent peripheral joint involvement
Since other studies demonstrated that expression levels of Vascular endothelial growth factor (VEGF) mRNA and protein were associated with severity of arthritis in Collagen-induced arthritis (CIA) mice [38], clinical data supported that VEGF plays a pivotal role in the pannus formation/angiogenesis in rheumatoid synovium [39]

Summary

Introduction

Axial spondyloarthritis (axSpA) comprised of ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) is an inflammatory disease of the axial skeleton. Anti-IL-17 treatment suppressed arthritis/spondylitis in both the initiating phase and established phase of the same SpA model and inhibited the periosteal new bone formation [23, 24]. Since other studies demonstrated that expression levels of VEGF mRNA and protein were associated with severity of arthritis in CIA mice [38], clinical data supported that VEGF plays a pivotal role in the pannus formation/angiogenesis in rheumatoid synovium [39].

Results

Conclusion