Canakinumab is used in gouty arthritis that is refractory to colchicine and NSAIDs. Its mechanism is:

• A Human monoclonal antibody against IL-6 receptor, blocking STAT3-mediated inflammatory amplification
• B Selective TNF-alpha neutralization, reducing neutrophil recruitment to synovial joints
• C Human monoclonal antibody against IL-1 beta, neutralizing the key cytokine activated by NLRP3 inflammasome in response to MSU crystals ✓
• D Inhibitor of JAK1/JAK2, reducing downstream CXCL8 and IL-8 production

Explanation

Monosodium urate (MSU) crystals activate the NLRP3 (NOD-like receptor protein 3) inflammasome in macrophages and neutrophils, leading to caspase-1 activation and subsequent IL-1beta maturation and secretion. IL-1beta is the master cytokine driving the acute gouty inflammation cascade. Canakinumab is a fully human IgG1 kappa monoclonal antibody that neutralizes IL-1beta with high affinity, providing durable (weeks to months) anti-inflammatory effect from a single subcutaneous injection. It is also used in CAPS (cryopyrin-associated periodic syndromes). Anakinra (recombinant IL-1 receptor antagonist) is an alternative.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.