← 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.
9 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.
Risk of Cancer According to Duration of Targeted Therapy Exposure in Spondyloarthritis: A Nationwide Cohort Study From the French Health Insurance Database
Arthritis & Rheumatology
Following 56,591 people with spondyloarthritis in France for a median of five years, those taking a targeted therapy for more than six months a year had slightly lower overall cancer risk than those taking it less. Staying on a TNF, IL-17 or JAK drug did not raise cancer risk in this very large real-world group, which addresses a common worry about long-term treatment.
Efficacy and safety of tofacitinib in ankylosing spondylitis patients: a systematic review and meta-analysis.
Clinics (Sao Paulo, Brazil)
Pooling the randomised trials of tofacitinib (Xeljanz) in ankylosing spondylitis, people on the drug were about twice as likely to reach the standard response targets, with gains in function and quality of life, and overall side-effect rates matched placebo apart from more upper respiratory infections. It confirms tofacitinib as an effective oral option, with colds and sinus infections the main trade-off.
Ivarmacitinib in patients with active ankylosing spondylitis: subgroup analysis based on key baseline features from a phase II/III trial.
Clinical rheumatology
Ivarmacitinib, a JAK inhibitor in late-stage trials, outperformed placebo in active ankylosing spondylitis regardless of age, sex, weight, disease duration, CRP level, pain severity or whether people had already failed a biologic or another JAK drug, and the benefit held to 24 weeks. Another oral option may be coming, and this analysis says it works across the board rather than only in a favourable subgroup.
Cardiovascular and Thromboembolic Risk With Upadacitinib in Spondyloarthritis and Inflammatory Bowel Disease: A Meta-Analysis of Randomized Controlled Trials.
Journal of cardiovascular pharmacology
Pooling eight randomised trials of 4,433 people with spondyloarthritis or inflammatory bowel disease, upadacitinib (Rinvoq) showed no increase in heart attacks, strokes or blood clots compared with placebo, though events were rare enough that the result cannot rule out a small risk. The signal that led to warnings on JAK drugs came from older rheumatoid arthritis patients; in this population, the trials so far are reassuring but not conclusive.
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.