natalizumab: clinical use

Prescribing considerations

• Initiate and supervise through clinicians experienced in neurological disease, with timely MRI access and facilities to manage hypersensitivity.
• Use as monotherapy for adults meeting the licensed highly active relapsing-remitting multiple-sclerosis criteria.
• Provide the Patient Card and discuss PML, infection and hypersensitivity symptoms with the patient and caregivers.
• Record the product name and batch number for biological-medicine traceability.
• Assess previous immunosuppressive exposure and confirm that the patient is not immunocompromised.

Contraindications and cautions

• Hypersensitivity to natalizumab or an excipient
• Current PML
• Increased risk of opportunistic infection, including immunocompromised states
• Combination with another disease-modifying therapy
• Known active malignancy, except cutaneous basal-cell carcinoma

Monitoring

• Obtain reference brain MRI before treatment and continue risk-adapted MRI surveillance.
• Check anti-JCV antibody status and index for PML risk stratification, with repeat testing determined by risk.
• Maintain clinical vigilance for new neurological, cognitive, psychiatric, visual or cerebellar features; suspend treatment and investigate promptly if PML is suspected.
• Observe for administration reactions as specified for the formulation and the patient's prior exposure.
• Assess unexplained infection, liver dysfunction, anaemia, thrombocytopenia or reduced effectiveness; persistent anti-natalizumab antibodies may reduce efficacy and increase hypersensitivity.

Clinical pharmacology

Natalizumab is a recombinant humanised monoclonal antibody that inhibits α4-integrin-mediated leukocyte adhesion and migration into inflamed tissue, including across the blood–brain barrier.

Formulation and product differences

• The intravenous product is a concentrate requiring dilution before infusion and must not be given as a bolus.
• The subcutaneous product is supplied in pre-filled syringes and must not be administered intravenously.
• Subcutaneous administration outside a clinical setting, including self- or caregiver administration, is restricted to appropriately selected, previously tolerant patients after supervised training.
• The intravenous formulation has clinically relevant sodium content after dilution; the subcutaneous formulation is essentially sodium-free. Both contain polysorbate 80, which may cause allergic reactions.

Solution for infusion

Route: Intravenous

Strengths: 300 mg

Injection

Route: Parenteral

Strengths: 150 mg