State-of-the-Art Review on the Treatment of Axial Spondyloarthritis

Abstract

The term axial spondyloarthritis (axSpA) encompasses patients with both radiographic (r-axSpA) and non-radiographic (nr-axSpA) forms of the disease. These are two entities within the same family that share many genetic and pathogenic factors, but they also have significant differences. For example, the male-to-female ratio is 2:1 in r-axSpA and 1:1 in nr-axSpA. Additionally, the prevalence of the HLA-B27 gene is notably higher in r-axSpA. Early diagnosis remains an unmet need, with magnetic resonance imaging (MRI) being the most important tool for diagnosis and disease monitoring. Early detection is crucial, as it allows for timely treatment, increasing the chances of preventing new bone formation and long-term structural bone damage. Various cytokines, such as tumor necrosis factor (TNF)-α and interleukin-17, play active roles in the disease's pathogenesis, although the exact mechanisms of interaction are not yet fully understood. Clarifying these mechanisms will be key to developing new classification criteria, screening methods, and more personalized, targeted therapies. Non-steroidal anti-inflammatory drugs (NSAIDs), TNF inhibitors, interleukin-17 blockers, and, more recently, Janus kinase (JAK) inhibitors, are the most effective treatments for both radiographic and non-radiographic axial spondyloarthritis.

Keywords: IL-17; IL-23; JAK inhibitors; TNF inhibitors; axial spondyloarthritis.

Figure 1

The implication of IL-23 and IL-17 in AxSpA. In AxSpA, IL-23 plays a central role in promoting inflammation, particularly with the axial skeleton (spine and sacroiliac joints). IL-23 is produced primarily by dendritic cells and macrophages in response to inflammation or tissue damage (a). In AxSpA, an overproduction of IL-23 occurs, which stimulates immune cells, particularly Th17 cells (b). These Th17 cells are crucial mediators of inflammation. Th17 cells produce another important cytokine, IL-17 (c). IL-17 acts on various tissues, particularly at sites like the entheses, leading to the development of enthesitis (d), a hallmark of AxSpA, causing pain and stiffness. IL-23 indirectly contributes to the dysregulated balance between bone erosion and bone formation seen in AxSpA. Inflammatory cells activated by IL-23 and IL-17 can trigger the activity of osteoclasts, leading to bone erosion at the affected joints (e). Conversely, chronic inflammation in AxSpA is also associated with abnormal new bone formation (syndesmophytes) in the spine, contributing to structural damage and spinal fusion over time (f).