JAK inhibitors: mechanism and safety
How JAK inhibitors block cytokine signalling through JAK-STAT, why receptor pairings predict their benefits and adverse effects, how their kinetics and clearance shape dosing, and what ORAL Surveillance changed about MACE, cancer and VTE risk.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Many cytokine receptors have no kinase of their own. They rely on associated Janus kinases (JAK1, JAK2, JAK3, TYK2) to phosphorylate STAT proteins, which dimerise and switch on genes in the nucleus.
- JAK inhibitors are oral small molecules that compete for the ATP-binding site. One drug therefore damps many cytokines at once.
- Which JAK pair a receptor uses predicts both benefit and harm. JAK2 block gives anaemia; JAK1/JAK3 block gives lymphopenia and zoster.
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Sources
- EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2025 updateAnnals of the Rheumatic Diseases, 2026
- Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis (ORAL Surveillance)New England Journal of Medicine (Ytterberg et al.), 2022
- Janus kinase inhibitors (JAKi): Article 20 referralEuropean Medicines Agency, 2022-23
- Points to consider for the treatment of immune-mediated inflammatory diseases with Janus kinase inhibitors: a consensus statementAnnals of the Rheumatic Diseases (Nash et al.), 2021
- Australian Medicines HandbookAU/NZAustralian Medicines Handbook Pty Ltd, 2026
- Pharmaceutical Benefits Scheme scheduleAU/NZAustralian Government Department of Health, Disability and Ageing, 2026
- Rinvoq (upadacitinib): EU summary of product characteristics, section 4.5 (rifampicin lowers upadacitinib Cmax by about 50% and AUC by about 60%)European Medicines Agency, current at November 2026
- The Australian Immunisation Handbook: zoster (herpes zoster)AU/NZAustralian Government Department of Health, Disability and Ageing, updated 12 November 2026
- Last updated
- 14 November 2026
What changed
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