Canakinumab

• Cryopyrin-Associated Periodic Syndromes (CAPS)
• Systemic Juvenile Idiopathic Arthritis
• Familial Mediterranean Fever
• Adult-Onset Still's Disease

Canakinumab is a human monoclonal antibody that selectively blocks interleukin-1 beta (IL-1β), a pro-inflammatory cytokine central to many autoinflammatory conditions. This biologic medication provides targeted treatment for several rare inflammatory diseases and has shown promise in reducing cardiovascular events.

Mechanism of Action

Canakinumab specifically binds to human IL-1β with high affinity, neutralizing its biological activity by blocking its interaction with IL-1 receptors. IL-1β is a key mediator of inflammatory responses, and its overproduction is central to the pathogenesis of autoinflammatory diseases. By selectively blocking IL-1β (without affecting IL-1α or the IL-1 receptor antagonist), canakinumab provides targeted suppression of IL-1β-driven inflammation. This results in rapid reduction of inflammatory markers such as C-reactive protein (CRP), serum amyloid A, and various clinical symptoms associated with autoinflammatory conditions.

Available Formulations

Canakinumab is available as a lyophilized powder for reconstitution (180 mg vials) and as a solution for subcutaneous injection in single-use vials (150 mg/mL). The reconstituted solution or prefilled syringe should be administered by a healthcare provider or trained individual. The medication requires refrigeration.

Medical Uses

Canakinumab is FDA-approved for Cryopyrin-Associated Periodic Syndromes (CAPS), including Familial Cold Autoinflammatory Syndrome (FCAS) and Muckle-Wells Syndrome (MWS); systemic juvenile idiopathic arthritis (SJIA) in patients aged 2 years and older; and active Still's disease, including adult-onset Still's disease. It is also approved for treating periodic fever syndromes including Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS), Hyperimmunoglobulin D Syndrome/Mevalonate Kinase Deficiency (HIDS/MKD), and Familial Mediterranean Fever (FMF). The CANTOS trial also demonstrated reduced cardiovascular events in high-risk patients.

Dosing Guidelines

Dosing varies by indication. For CAPS: 150 mg (or 2 mg/kg for patients 15-40 kg) subcutaneously every 8 weeks. For SJIA: 4 mg/kg (maximum 300 mg) subcutaneously every 4 weeks. For Still's disease: 4 mg/kg (maximum 300 mg) subcutaneously every 4 weeks. For periodic fever syndromes: 150 mg (or 2 mg/kg for patients ≤40 kg) every 4 weeks, with possible increase to 300 mg or every 4-week dosing if needed. Responses are typically seen within days to weeks.

Important Safety Information

Canakinumab increases the risk of serious infections, including opportunistic infections. Treatment should not be initiated during active infections, and patients should be monitored closely. Tuberculosis screening is required before starting therapy. Live vaccines should not be given during treatment; all recommended vaccinations should be completed before starting therapy. Macrophage activation syndrome (MAS), a potentially fatal condition, has been reported in SJIA patients. Hypersensitivity reactions may occur.

Drug Interactions

IL-1 blockade may affect the expression of CYP450 enzymes. When starting or stopping canakinumab, therapeutic monitoring should be performed for medications metabolized by CYP450 with narrow therapeutic indices (warfarin, cyclosporine, theophylline). Concurrent use with TNF inhibitors is not recommended due to increased infection risk. Live vaccines should not be administered during treatment. No formal drug interaction studies have been conducted.

Special Populations

There are limited data on use during pregnancy; animal studies showed no evidence of harm. The medication should be used during pregnancy only if clearly needed. It is unknown whether canakinumab is excreted in human breast milk. Safety and efficacy have been established in pediatric patients for CAPS (4 years and older) and SJIA (2 years and older). Clinical trials included limited numbers of elderly patients; no overall differences in safety were observed. No dose adjustment is needed for renal impairment. The medication has not been studied in patients with hepatic impairment.