Canakinumab

Canakinumab is a human monoclonal IgG1 antibody that neutralises interleukin 1 beta, given subcutaneously every 4 to 8 weeks, used in cryopyrin-associated periodic syndromes, TNF receptor-associated periodic syndrome, mevalonate kinase deficiency, familial Mediterranean fever resistant to colchicine, Still disease and acute gout flares when other options are contraindicated.

Class. Interleukin 1 beta inhibitor monoclonal antibody.

Mechanism. It binds interleukin 1 beta with high affinity and blocks its interaction with interleukin 1 receptors, without binding interleukin 1 alpha or the receptor antagonist.

Pharmacokinetics. Subcutaneous bioavailability about 70 percent, peak at about 7 days, half-life about 26 days. Clearance increases with body weight.

Cryopyrin-associated periodic syndromes (children from 2 years and adults).

• Over 40 kg: 150 mg subcutaneously every 8 weeks.

• 15 to 40 kg: 2 mg/kg every 8 weeks.

• Under 15 kg (off label in some regions): 4 mg/kg every 8 weeks.

• Increase for inadequate response: 300 mg (over 40 kg) or 3 mg/kg (15 to 40 kg).

TNF receptor-associated periodic syndrome, hyperimmunoglobulin D syndrome, mevalonate kinase deficiency, and colchicine-resistant familial Mediterranean fever.

• Over 40 kg: 150 mg every 4 weeks, increasing to 300 mg every 4 weeks if no response after 7 days.

• 40 kg or less: 2 mg/kg every 4 weeks, increasing to 4 mg/kg every 4 weeks if needed.

Still disease (systemic juvenile idiopathic arthritis and adult-onset, 2 years and over, 7.5 kg and over). 4 mg/kg (maximum 300 mg) every 4 weeks.

Acute gout flare (when NSAIDs and colchicine are contraindicated or ineffective, and repeated courses of glucocorticoid are unsuitable). 150 mg single subcutaneous dose; do not repeat for at least 12 weeks.

Loading dose. None.

Maximum dose. 300 mg for each dose; weight-based doses should not exceed 300 mg.

Contraindications. Hypersensitivity to canakinumab and active serious infection.

Boxed-warning-level risks. No boxed warning. Serious infection (including tuberculosis and opportunistic infection) and neutropenia are the main hazards.

Adverse effects. Common: upper respiratory infection, nasopharyngitis, injection site reactions, headache, vertigo. Serious: serious infection, neutropenia and thrombocytopenia, hypersensitivity, macrophage activation syndrome, raised liver enzymes.

Major interactions. TNF inhibitors and other biologics (avoid), live vaccines (avoid; give inactivated vaccines before starting), and cytochrome P450 substrates with narrow indices (warfarin, ciclosporin) as inflammation resolves.

Common prescribing errors. Using for gout flares as first line; repeating the gout dose within 12 weeks; combining with TNF inhibitors.

Special groups.

• Pregnancy: limited data; avoid unless needed. Contraception during treatment and for 3 months after the last dose. Delay live vaccines in infants for 4 months after late exposure.

• Breastfeeding: limited data; likely low transfer.

• Children: weight-based as stated.

• Older adults: no adjustment.

• Kidney impairment: no adjustment expected.

• Liver impairment: no adjustment expected; monitor enzymes.

• Region: screen for tuberculosis and hepatitis B; refrigerated storage and cost limit access.

Formulations. 150 mg/mL solution in vials (draw up for weight-based doses) and 150 mg prefilled syringes. Inject subcutaneously into the thigh, abdomen or upper arm. Store at 2 to 8 degrees Celsius.

Baseline. Neutrophils, platelets, tuberculosis screen, hepatitis B and C and HIV serology, liver enzymes, and vaccination update.

Monitoring. Full blood count and liver enzymes at 1 to 2 months then every 3 to 6 months. Disease activity (fever, rash, inflammatory markers) at each visit.

Stop or hold thresholds. Serious infection (hold until resolved), neutrophils under 1.0 x 10^9/L, severe hypersensitivity, or macrophage activation syndrome.

Referral and escalation. Specialist initiated. Refer for recurrent infection or inadequate response.