Ankylosing Spondylitis (Axial Spondyloarthritis)
Ankylosing spondylitis, now correctly termed axial spondyloarthritis (axSpA), is a chronic inflammatory disease primarily affecting the spine and sacroiliac joints. Typical features are chronic back pain that improves with movement and worsens at rest (inflammatory back pain), morning stiffness, and progressive spinal fusion through ossification (ankylosis). The disease usually begins in young adulthood and is strongly associated with the genetic marker HLA-B27 (about 85–95% of affected individuals carry this gene).
Immunologically, the IL-23/IL-17 axis is central: At the entheses (the sites where tendons and ligaments attach to bone), there are IL-23-responsive immune cells, including γδ T cells and ILC3 (innate lymphoid cells type 3), which produce IL-17 — interestingly often independently of classical Th17 cells. IL-17 promotes both inflammation and pathological new bone formation (syndesmophytes) leading to spinal fusion. TNF-α also plays an important role in sacroiliac joint inflammation and peripheral arthritis.
Biologics: Anti-TNF (infliximab, adalimumab, etanercept, golimumab, certolizumab) are the first approved biologic class and highly effective against pain and inflammation. Anti-IL-17A (secukinumab, ixekizumab) are also approved and particularly effective for axial inflammation. JAK inhibitors: Upadacitinib (JAK1) and tofacitinib (JAK1/3) are approved. However, anti-IL-23 antibodies (risankizumab) surprisingly showed no efficacy in axial SpA in studies — suggesting that IL-17 production at the entheses is partly IL-23-independent.