Emicizumab

Emicizumab is a bispecific monoclonal antibody that mimics the function of activated factor VIII. It is given subcutaneously as prophylaxis in haemophilia A, with or without factor VIII inhibitors, and has no use in acute bleeding.

Classification. Bispecific monoclonal antibody; factor VIII mimetic.

Mechanism. Binds activated factor IX and factor X, bringing them together in place of factor VIIIa and restoring the tenase complex function. It is unrelated to factor VIII and unaffected by inhibitors.

Pharmacokinetics. Subcutaneous bioavailability is about 80 to 93%. Half-life is about 4 to 5 weeks. Steady state is reached after about 4 weeks of loading.

Routine prophylaxis in haemophilia A (all ages, with or without inhibitors).

• Loading dose: 3 mg/kg subcutaneously once weekly for the first 4 weeks.
• Maintenance, one of: 1.5 mg/kg once weekly; 3 mg/kg every 2 weeks; or 6 mg/kg every 4 weeks.
• Maximum: 6 mg/kg for each dose. A single injection is limited to 2 mL; larger doses are split between sites. Titration: dose-change is by weight only.

Breakthrough bleeds. Treat with factor VIII (if no inhibitor) or recombinant activated factor VII (with inhibitors). Avoid activated prothrombin complex concentrate where possible.

Surgery. Minor procedures can often proceed without added cover; major surgery requires factor VIII or recombinant activated factor VII.

Adjustments. Kidney and liver: no adjustment. Age: licensed from birth in many regions. Pregnancy and breastfeeding: limited data.

Contraindications. Hypersensitivity. Not for haemophilia B or acquired haemophilia.

Boxed-warning-level risk. Thrombotic microangiopathy and thromboembolism, mainly when activated prothrombin complex concentrate was given at an average of over 100 units/kg daily for 24 hours or more. Stop the concentrate and monitor; use recombinant activated factor VII for bleeds if possible.

Adverse effects. Injection-site reaction, headache, arthralgia, fever. Anti-drug antibodies are rare.

Interactions. Activated prothrombin complex concentrate (major risk); other procoagulants. Emicizumab normalises the activated partial thromboplastin time in haemophilia A, makes one-stage factor VIII assays unreliable, and interferes with Bethesda assays; use chromogenic assays with bovine reagents.

Pregnancy and breastfeeding. Use only if the benefit clearly outweighs the risk.

Regional points. Cost and supply limit use in East Africa; patients on it still need access to factor VIII or recombinant activated factor VII for bleeds.

Common errors. Using activated prothrombin complex concentrate as the default; using one-stage assays to monitor factor VIII; stopping loading doses early.

Administration. Subcutaneous injection into the abdomen, upper outer arm or thigh, rotating sites. Store vials at 2 to 8°C, in the original carton, protected from light; vials may be kept at room temperature for up to 7 days.

Baseline. Factor VIII level, inhibitor titre by chromogenic assay, bleeding history, joint assessment, hepatitis B, hepatitis C and HIV status.

Monitoring. Bleeding diary and joint assessment every 3 to 6 months; inhibitors by chromogenic assay if bleeding rises; renal function, haemoglobin and platelets if activated prothrombin complex concentrate is used.

Referral and escalation. Refer any thrombotic event, thrombotic microangiopathy (falling platelets, haemolysis, kidney injury) or breakthrough bleeding to a haemophilia centre; stop activated prothrombin complex concentrate.