Natalizumab
Multiple sclerosis disease-modifying therapies
Multiple sclerosis disease-modifying therapies
A monthly infused antibody against alpha-4 integrin that keeps lymphocytes out of the brain; its key risk is PML from the JC virus.
Also called: Natalizumab-sztn
Quick facts
- Group
- Multiple sclerosis disease-modifying therapies
- Target
- Alpha-4 integrin (α4β1 and α4β7)
- Used for
- Relapsing forms of multiple sclerosis
- Key effects
- Headache and tiredness · Joint and limb pain · Urinary
- Monitor
- Anti-JC virus antibodies before
- ATC
- L04AG03
No doses: the clinician sets them by the current guideline.
Mechanism of action
The figure shows the Fab fragment of natalizumab bound to the alpha-4 subunit of the α4β7 integrin headpiece; the drug is the antibody itself, so there is no small ligand.
Natalizumab is a humanized monoclonal antibody against the alpha-4 subunit shared by α4β1 and α4β7 integrins on leukocytes. The interaction of α4β1 with VCAM-1 on endothelial cells is needed for T cells to cross the blood-brain barrier; blocking it strongly reduces inflammatory cell entry into the CNS. Blocking α4β7 with MAdCAM-1 reduces homing to the inflamed gut, the basis of its use in Crohn disease.
- Natalizumab binds alpha-4 integrin on leukocytes
- α4β1 can no longer bind VCAM-1 on brain vessels
- T cells fail to cross the blood-brain barrier
- Fewer relapses, but less immune surveillance of the brain
Indications
- Relapsing forms of multiple sclerosis (including active secondary progressive) Multiple sclerosis →
- Moderate to severe Crohn disease not controlled by other treatments Crohn disease →
Adverse effects
Common
- Headache and tiredness
- Joint and limb pain
- Urinary, respiratory and vaginal infections
- Rash and diarrhoea
Contraindications
- Allergy to natalizumab
- Current or previous PML, or conditions that weaken immunity (HIV, leukaemia, lymphoma, organ transplant), usually rule it out
Key interactions
- Immunosuppressants (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate), now or in the past
- Higher risk of PML and other infections
- Plasma exchange
- An anti-JCV antibody test is not reliable within 2 weeks of plasma exchange
What is monitored
- Anti-JC virus antibodies before and periodically during treatment
- Questions about new neurological symptoms before every infusion, and for 6 months after the last dose
- MRI if PML is suspected
- Liver tests and blood counts as needed
Administration and safety
- Given only in registered infusion centres within a restricted distribution programme
- Intravenous infusion over about one hour, every 4 weeks
- Observation for 1 hour after the infusion, at least for the first 12 infusions
Nursing care
- Before each infusion: ask about fever, infection, shingles and new neurological symptoms
- During and after the infusion: watch for hives, itching, wheeze, trouble breathing, dizziness, chest pain, flushing
- Teach PML warning signs: one-sided weakness that worsens, clumsiness, changes in thinking, memory, vision or personality
- Teach signs of liver injury and low platelets
Pharmacokinetics
- Absorption
- Intravenous infusion over about an hour
- Elimination
- Long-acting antibody, given every 4 weeks
Test yourself
Think of the answer, then tap the question to see it.
What does natalizumab bind?
The alpha-4 subunit of α4β1 and α4β7 integrins on leukocytes.
Which three factors raise the risk of PML on natalizumab?
Anti-JCV antibodies, longer treatment (more than 2 years) and previous immunosuppressants.
Besides MS, which disease is natalizumab used for?
Crohn disease.
How long are patients observed after an infusion in the first months?
One hour after the infusion, for at least the first 12 infusions.
Connections
← Back to the class: Multiple sclerosis disease-modifying therapies
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Natalizumab Injection: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 4IRZ: Crystal structure of A4b7 headpiece complexed with Fab Natalizumab (RCSB Protein Data Bank, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.