← Map/THREAD · JAK-STAT
JAK–STAT Pathway
The newer oral pill option, tofacitinib, upadacitinib, filgotinib.
Why this is a thread
JAK inhibitors are the newer oral pill option for AS, tofacitinib (Xeljanz), upadacitinib (Rinvoq), filgotinib (Jyseleca). They work by blocking a signalling pathway inside cells that several inflammatory signals share. Current guidelines mostly place them after TNF and IL-17 blockers, with one exception: when AS comes alongside inflammatory bowel disease, JAK inhibitors are sometimes recommended earlier in the sequence. This thread tracks where JAK inhibitors fit in the treatment hierarchy, including what real-world data is showing about their safety profile.
5 papers on the board
Current status and emerging trends in biological therapies for ankylosing spondylitis: a bibliometric analysis (2004–2024)
Medicine (LWW)
Bibliometric analysis of biological therapies for AS over 2004-2024. Confirms three pillars, TNF, IL-17, and JAK inhibitors, and a persistent inadequate response in a meaningful subset of patients across all three classes.
Recent advances in biologic therapies for ankylosing spondylitis: a 2024 update
Allergologia et Immunopathologia
Comprehensive bDMARD review covering TNF, IL-17, and JAK inhibitor classes with their efficacy and safety profiles across the AS treatment landscape. Confirms a meaningful patient subset still has inadequate response across all three drug classes.
Advances in Axial Spondyloarthritis Treatment: The Role of Janus Kinase Inhibitors
International Journal of Rheumatic Diseases
Reviews the JAK inhibitor class, tofacitinib, upadacitinib, filgotinib, for axial spondyloarthritis. The 2025 CRA/SPARCC guidelines still place TNF inhibitors first-line, with JAK inhibitors recommended when TNFi is contraindicated or for patients with comorbid IBD.
Efficacy of JAK inhibitors in immune-mediated inflammatory diseases: 2024 update of an international consensus statement
Annals of the Rheumatic Diseases
Systematic literature review of JAK inhibitor efficacy across immune-mediated inflammatory diseases. Effective broadly, but isoform selectivity (JAK1/2/3/TYK2) and the data on tapering or withdrawal remain unclear.
Macrophage polarization: molecular mechanisms, disease implications, and targeted therapeutic strategies
Frontiers in Immunology
Reviews macrophage polarisation, the molecular mechanisms behind it, and emerging therapeutic strategies. Persistent M1 polarisation as the common driver of chronic disease, with JAK/STAT inhibition as a candidate way to restore the M1→M2 transition.