Canakinumab is used for prevention of gout flares and atherosclerotic events. Its mechanism involves:
- A Inhibition of xanthine oxidase, reducing uric acid production
- B Blockade of URAT1 uric acid transporter in the proximal tubule, promoting uricosuria
- C Selective monoclonal antibody neutralisation of IL-1beta, blocking NLRP3 inflammasome-mediated gout inflammation ✓
- D Inhibition of tubulin polymerisation, preventing neutrophil migration into joints
Explanation
Canakinumab is a fully human IgG1 monoclonal antibody that specifically targets and neutralises IL-1beta. In gout, monosodium urate crystals activate the NLRP3 inflammasome in macrophages, leading to caspase-1 activation and IL-1beta processing and release. IL-1beta then drives the acute inflammatory cascade. By neutralising IL-1beta, canakinumab rapidly reduces gout flare severity and was shown in the CANTOS trial to reduce cardiovascular events, highlighting the role of IL-1beta in atherosclerotic plaque instability. Xanthine oxidase inhibition is allopurinol/febuxostat; URAT1 blockade is lesinurad/benzbromarone; tubulin inhibition is colchicine.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.