Advances in Axial Spondyloarthritis Treatment: The Role of Janus Kinase Inhibitors

Axial spondyloarthritis (axSpA) is a chronic inflammatory disease affecting the spine, peripheral joints and entheses, driven by dysregulated immune cell pathways, particularly the Janus kinase-signal transducer and activator of transcription (JAK‑STAT) pathway. While non‑steroidal anti‑inflammatory drugs and biologic disease-modifying anti-rheumatic drugs (DMARDs) (e.g., tumour necrosis factor inhibitors [TNFi] and interleukin inhibitors [IL‑17i]) are standard treatments. However, many patients show inadequate responses, necessitating alternative therapies. JAK inhibitors (JAKi), including tofacitinib, upadacitinib and filgotinib, offer targeted benefits by blocking the JAK‑STAT pathway to reduce pro-inflammatory cytokine transcription. Clinical trials have demonstrated that tofacitinib significantly improves ankylosing spondylitis outcomes, achieving superior Assessment of Spondyloarthritis International Society 20 and 40 (ASAS20 and ASAS40) responses compared to placebo. Upadacitinib has consistently shown efficacy across both radiographic and non‑radiographic axSpA in the SELECT‑AXIS trials, while the phase II TORTUGA trial reported that filgotinib significantly reduced disease activity, with greater improvements in ASDAS and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) scores compared to placebo. Mild side effects, such as nasopharyngitis and increased creatine phosphokinase levels, have been observed without conclusive links to severe adverse events like malignancies or cardiovascular complications. Thorough screening for tuberculosis and viral hepatitis is essential before initiating JAKi therapy. Moreover, for patients with comorbid inflammatory bowel disease, where TNFi may be unsuitable, tofacitinib provides an effective alternative. Its oral formulation enhances patient compliance and, combined with favourable cost‑effectiveness data, positions JAKi as attractive alternatives to conventional biologic therapies. Current evidence suggests that JAKi are a promising option for axSpA patients unresponsive to conventional or biologic DMARDs. However, long-term studies are needed to compare their efficacy and safety with TNFi and IL-17i.