Last updated on November 18th, 2025 at 06:25 pm
Summary
Natalizumab is a first-in-class selective adhesion molecule blocker that reduces the trafficking of lymphocytes into the central nervous system (CNS). It is a very high-efficacy DMT capable of achieving long-term NEIDA (no evident inflammatory disease activity) and limiting end-organ damage (brain volume loss) in most people with MS who receive it. Following rebaselining, average annual brain volume loss for patients treated with natalizumab is within the expected range for age-matched people without MS. Natalizumab has a rapid onset of action; when it is used early in the disease course, many people with MS report a reduction in symptoms of disability and fatigue.
One result of reduced lymphocyte trafficking in the brain is reduced immune surveillance. This puts patients receiving natalizumab at high risk of progressive multifocal leukoencephalopathy (PML) if infected with the JC virus that causes it. The risk of PML is variable and can be reduced by using extended interval dosing (EID), whereby natalizumab is given as a 6-weekly infusion and is very well tolerated. (Normally natalizumab is given every 4 weeks.) A small number of people with MS (<5%) may develop infusion reactions, which can be serious. Infusion reactions typically come on with the second, third or fourth natalizumab infusion and are associated with developing so-called neutralising antibodies (NAbs).
Trade name
Tysabri.
Mode of action
Natalizumab is an immunosuppressive, and it is associated with opportunistic infections and possibly secondary malignancies of the central nervous system (CNS). Natalizumab blocks one of the surface molecules on lymphocytes so that they cannot cross the blood ̶ brain barrier.
Efficacy
Very high, particularly in people with rapidly evolving severe MS.
Class
Maintenance, immunosuppressive.
Immunosuppression
Yes, but limited to the CNS.
Dosing
- Natalizumab 300 mg is administered by intravenous infusion or subcutaneous injection once every 4 weeks.
- Extended interval dosing (EID), decreasing the frequency of infusions to every 6 weeks, reduces the risk of PML.
Main adverse events of special interest
- Infusion reactions; hypersensitivity reactions with repeated infusion of the drug.
- JC virus (JCV), the commonest opportunistic infection, causes progressive multifocal leukoencephalopathy (PML) and granule cell neuronopathy. Management of PML is described separately.
- Other opportunistic infections include cryptosporidium diarrhoea, cryptococcal meningitis, life-threatening encephalitis and meningitis.
- CNS lymphoma is a risk because of reduced immune surveillance.
Pharmacovigilance monitoring requirements
- Tests for liver function, neutralising antibodies, JCV.
- Rebaseline magnetic resonance imaging (MRI) 3 ̶ 6 months after starting treatment and increased MRI monitoring where PML risk is high.
- Self-monitoring for opportunistic infections; monthly breast checks.
- Live vaccines can infect the CNS and are contraindicated.
Further details about natalizumab