The role of IL-17A in axial spondyloarthritis and psoriatic arthritis: recent advances and controversies

Abstract

Although the pathogenic mechanisms underlying axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) are not fully elucidated, several lines of evidence suggest that immune responses mediated by interleukin 17A (IL-17A) play a pivotal role in both diseases. This is best highlighted by the significant clinical efficacy shown with inhibitors of IL-17A in treating axSpA and PsA. Nevertheless, a number of knowledge gaps exist regarding the role of IL-17A in the pathophysiology of spondyloarthritis in man, including its cellular origin, its precise role in discrete disease processes such enthesitis, bone erosion, and bone formation, and the reasons for the discrepant responses to IL-17A inhibition observed in certain other spondyloarthritis manifestations. In this review, we focus on the latest data from studies investigating the role of IL-17A in ankylosing spondylitis (AS) and PsA that build on existing and emerging scientific knowledge in the field. Key remaining research questions are also highlighted to guide future research.

Secukinumab efficacy in patients with PsA is not dependent on patients' body mass index

“…We read with interest the recently published paper from McGonagle et al 1 analysing the role of interleukin (IL)-17A in axial spondyloarthritis and psoriatic arthritis (PsA). The meta-analysis and functional study provided by the authors highlighted the efficacy of IL-17A block by secukinumab in the treatment of PsA.…”

Interleukin‐23 pathway at the enthesis: The emerging story of enthesitis in spondyloarthropathy

“…This functional tissue arrangement is termed a synovio‐entheseal complex, which are very common in the peripheral skeleton but uncommon in the spinal entheseal network . As discussed later, IL‐23 blockers appear to be efficacious for peripheral enthesitis but not for spinal involvement and the differing immune cell compositions of both types of enthesis may yet prove relevant for understanding the dichotomous therapeutic findings . In addition to the elaborate synovio‐entheseal complexes, the anchorage of the enthesis organ to the skeleton involves long‐distance bone trabecular struts reaching deep into the osseous compartment.…”

“…31 As discussed later, IL-23 blockers appear to be efficacious for peripheral enthesitis but not for spinal involvement and the differing immune cell compositions of both types of enthesis may yet prove relevant for understanding the dichotomous therapeutic findings. 44 In addition to the elaborate synovio-entheseal complexes, the anchorage of the enthesis organ to the skeleton involves long-distance bone trabecular struts reaching deep into the osseous compartment. Indeed, the bony anchorage of the enthesis may be viewed like the roots of a tree hidden below the surface.…”

<p>Therapeutic Potential of Ixekizumab in the Treatment of Ankylosing Spondylitis: A Review on the Emerging Clinical Data</p>

“…22 Anyway, other data support an inhibitory role for IL-17A on osteoblasts, 23 thus leaving space for further investigations on this topic. 24 Talking about SA extra-articular manifestations, a role of IL-17 in uveitis pathogenesis is quite probable; high levels of IL-17A have been found in aqueous, vitreous and serum of patients with anterior uveitis. 25 Moreover, γδ T cells have been detected in the ciliary body of SA mice models and the same finding was made at the side of the cardiac valves.…”