Belimumab

Belimumab is a human monoclonal IgG1 antibody that inhibits B lymphocyte stimulator (BLyS), given intravenously or subcutaneously, used as add-on therapy in systemic lupus erythematosus and in active lupus nephritis. It reduces flares and steroid requirement and slows organ damage accrual.

Class. B lymphocyte stimulator inhibitor monoclonal antibody.

Mechanism. Binds soluble BLyS and prevents it engaging B cell receptors, reducing survival of autoreactive B cells and their differentiation into plasma cells.

Pharmacokinetics. Intravenous half-life about 19 to 20 days. Subcutaneous bioavailability about 74 percent. Clearance is higher with proteinuria and high body weight.

Systemic lupus erythematosus (add-on to conventional therapy).

• Intravenous: 10 mg/kg over 1 hour on days 0, 14 and 28, then every 4 weeks.

• Subcutaneous: 200 mg once weekly.

• Switching from intravenous to subcutaneous: give the first subcutaneous dose 1 to 4 weeks after the last intravenous dose.

• Maximum dose: 10 mg/kg intravenously; 200 mg subcutaneously each week.

Active lupus nephritis (with glucocorticoid and mycophenolate or low dose cyclophosphamide).

• Intravenous: 10 mg/kg at days 0, 14 and 28, then every 4 weeks.

• Subcutaneous: 400 mg (two 200 mg injections) once weekly for 4 doses, then 200 mg once weekly.

Paediatric systemic lupus erythematosus (5 years and over). 10 mg/kg intravenously on days 0, 14 and 28 and then every 4 weeks. Subcutaneous paediatric dosing is weight-banded and specialist directed.

Response review. Continue only if disease control improves within 6 months.

Contraindications. Prior anaphylaxis to belimumab.

Boxed-warning-level risks. No boxed warning. Main hazards are serious infection, depression and suicidality, hypersensitivity (including delayed reactions) and progressive multifocal leukoencephalopathy.

Adverse effects. Common: nausea, diarrhoea, fever, nasopharyngitis, bronchitis, insomnia, depression, migraine, infusion and injection site reactions. Serious: serious infection, anaphylaxis, psychiatric events including suicidal ideation, leucopenia, malignancy (uncertain).

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

Common prescribing errors. Not screening for depression; using in severe active central nervous system lupus; omitting observation after infusion.

Special groups.

• Pregnancy: limited data; use effective contraception during treatment and for 4 months after the last dose.

• Breastfeeding: limited data; likely low milk transfer.

• Children: 10 mg/kg intravenously from 5 years.

• Older adults: no adjustment; closer infection monitoring.

• Kidney impairment: no adjustment; used in lupus nephritis.

• Liver impairment: no adjustment expected.

• Region: screen for tuberculosis, hepatitis B and HIV; availability and cost limit use.

Formulations. 120 mg and 400 mg intravenous vials (reconstitute with sterile water, dilute to 250 mL in 0.9 percent sodium chloride, infuse over 1 hour); 200 mg prefilled pen or syringe for subcutaneous use. Store at 2 to 8 degrees Celsius. Premedication with an antihistamine, with or without paracetamol, is advised.

Baseline. Mood and suicidality screen, full blood count, creatinine and urine protein for nephritis, immunoglobulins, hepatitis B and C and HIV serology, and tuberculosis screen.

Monitoring. Observe for at least 1 hour after the first 2 intravenous infusions. Disease activity, mood and infection at each visit. Urine protein to creatinine ratio and creatinine in nephritis.

Stop or hold thresholds. Anaphylaxis, serious infection, new suicidal ideation, or progressive multifocal leukoencephalopathy.

Referral and escalation. Specialist initiated. Refer for psychiatric symptoms or no response by 6 months.