Anakinra

Anakinra is a recombinant human interleukin 1 receptor antagonist given by daily subcutaneous injection, used in rheumatoid arthritis, cryopyrin-associated periodic syndromes, Still disease, deficiency of the interleukin 1 receptor antagonist, recurrent pericarditis and, off label, gout flares, familial Mediterranean fever resistant to colchicine, macrophage activation syndrome and cytokine storm. The short half-life allows rapid withdrawal if infection occurs.

Class. Interleukin 1 receptor antagonist, biological agent.

Mechanism. It competitively binds the interleukin 1 type I receptor and blocks the actions of both interleukin 1 alpha and beta.

Pharmacokinetics. Subcutaneous bioavailability about 95 percent, peak at 3 to 7 hours, half-life 4 to 6 hours, renal clearance, so exposure rises when creatinine clearance falls.

Rheumatoid arthritis (after inadequate response to methotrexate).

• 100 mg subcutaneously once daily, at about the same time each day.

• Loading dose: none.

• Maximum dose: 100 mg daily in this indication.

Cryopyrin-associated periodic syndromes. Start 1 to 2 mg/kg once daily; increase in 0.5 to 1 mg/kg steps to a maximum of 8 mg/kg daily in severe disease; adults 1 to 2 mg/kg is typical (100 mg daily in mild disease).

Still disease (systemic juvenile idiopathic arthritis and adult-onset). 100 mg once daily in adults; 1 to 2 mg/kg once daily in children (up to 100 mg), titrated by response.

Deficiency of the interleukin 1 receptor antagonist. 1 to 2 mg/kg once daily, increasing to a maximum of 8 mg/kg daily as needed.

Recurrent pericarditis (specialist). 100 mg once daily for adults for at least 6 months, then taper; 1 to 2 mg/kg daily (maximum 100 mg) in children.

Gout flare (off label, when other drugs are contraindicated). 100 mg once daily for 3 days.

Colchicine-resistant familial Mediterranean fever (off label). 100 mg once daily, specialist directed.

Macrophage activation syndrome or cytokine storm (off label, critical care and specialist). Intravenous or subcutaneous doses of 2 to 8 mg/kg daily are used; this regimen is not licensed and needs specialist oversight.

Renal dose adjustment. Creatinine clearance under 30 mL/min: consider 100 mg every other day. Dialysis: every other day.

Contraindications. Hypersensitivity to anakinra or to Escherichia coli-derived proteins, and neutropenia (neutrophils under 1.5 x 10^9/L). Avoid in active serious infection.

Boxed-warning-level risks. No boxed warning in most regions. Serious infection and neutropenia are the main hazards.

Adverse effects. Common: injection site reactions (very common, mostly in the first month), headache, upper respiratory infection, raised cholesterol. Serious: serious infection, neutropenia, hypersensitivity, raised liver enzymes, macrophage activation syndrome in Still disease (paradoxical).

Major interactions. TNF inhibitors and other biologics (avoid; serious infection and neutropenia without added benefit), live vaccines (avoid), and cytochrome P450 substrates with narrow indices (warfarin, ciclosporin) when inflammation resolves.

Common prescribing errors. Using the rheumatoid arthritis dose for periodic fever syndromes; not reducing frequency in renal impairment; combining with TNF inhibitors; missing neutrophil monitoring.

Special groups.

• Pregnancy: limited data; use only if needed and benefit outweighs risk.

• Breastfeeding: limited data; likely low transfer, use with caution.

• Children: 1 to 2 mg/kg daily as stated.

• Older adults: lower renal function; adjust the interval.

• Kidney impairment: every other day for creatinine clearance under 30 mL/min.

• Liver impairment: no adjustment; monitor enzymes.

• Region: daily injection needs refrigerated storage and safe sharps disposal; tuberculosis and hepatitis B screening before starting.

Formulations. 100 mg prefilled syringes (0.67 mL), graduated for smaller doses in children. Inject subcutaneously into the thigh, abdomen or upper arm, rotating sites. Store at 2 to 8 degrees Celsius; may be kept at room temperature for up to 12 hours.

Baseline. Neutrophil count, tuberculosis screen, hepatitis B and C and HIV serology, liver enzymes, creatinine, and vaccination update.

Monitoring. Neutrophils before starting, monthly for 3 months, then every 3 months for the first year. Liver enzymes and creatinine periodically. Disease activity and infection symptoms at each visit.

Stop or hold thresholds. Neutrophils under 1.5 x 10^9/L (hold), serious infection (hold until resolved), severe hypersensitivity, or no response in 1 to 3 months in periodic fever syndromes.

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