Anifrolumab

Anifrolumab is a human monoclonal IgG1 antibody that blocks the type I interferon receptor, used as add-on therapy for moderate to severe systemic lupus erythematosus despite conventional treatment. It reduces global disease activity, skin activity and glucocorticoid requirement.

Class. Type I interferon receptor antagonist monoclonal antibody.

Mechanism. It binds subunit 1 of the type I interferon receptor and blocks signalling by all type I interferons, which are overexpressed in most patients with lupus.

Pharmacokinetics. Intravenous only, with nonlinear clearance and half-life of about 21 days at 300 mg. Steady state by about 16 weeks.

Moderate to severe systemic lupus erythematosus (add-on).

• 300 mg intravenously over 30 minutes every 4 weeks.

• Loading dose: none.

• Maximum dose: 300 mg for each infusion.

• Duration: long term while disease control and tolerability are maintained; reassess at 6 to 12 months.

Glucocorticoid taper. Taper prednisolone to 7.5 mg daily or less during treatment where disease control allows.

Contraindications. Prior anaphylaxis to anifrolumab. Avoid in active serious infection.

Boxed-warning-level risks. No boxed warning. Main hazards are herpes zoster, respiratory infection, hypersensitivity and infusion reactions, and uncertain malignancy risk.

Adverse effects. Common: upper respiratory infection, bronchitis, infusion reactions, herpes zoster, cough. Serious: serious infection (including herpes zoster and tuberculosis reactivation), anaphylaxis, malignancy (uncertain).

Major interactions. Live vaccines (avoid). Not studied with other biologics or intravenous cyclophosphamide; avoid combining.

Common prescribing errors. Using in severe active lupus nephritis or central nervous system lupus (not studied at licensing); missing recombinant zoster vaccination before starting.

Special groups.

• Pregnancy: avoid; contraception during treatment and for 3 months after the last dose.

• Breastfeeding: limited data; avoid.

• Children: not established.

• Older adults: no adjustment; monitor for infection.

• Kidney impairment: no adjustment.

• Liver impairment: no adjustment expected.

• Region: screen for tuberculosis, hepatitis B and HIV; cold chain and availability should be confirmed.

Formulations. 300 mg intravenous vial, diluted to 100 mL in 0.9 percent sodium chloride and infused over 30 minutes through a low protein binding filter. Store at 2 to 8 degrees Celsius and protect from light.

Baseline. Tuberculosis screen, hepatitis B and C and HIV serology, full blood count, creatinine and urine protein, varicella zoster immunity, and vaccination update including recombinant zoster vaccine.

Monitoring. Observe during and after the first infusions. Disease activity, infection symptoms and herpes zoster at each visit; periodic full blood count.

Stop or hold thresholds. Anaphylaxis, serious infection, or malignancy. Hold during active serious infection.

Referral and escalation. Specialist initiated. Refer for inadequate response at 6 months.