What is the classification of natalizumab? Understanding its class and function

October 9, 2025 •

2 min read

Natalizumab, an immunosuppressant, was temporarily withdrawn from the market in 2005 due to safety concerns regarding a rare brain infection, before being re-approved with a restricted program in 2006. Its classification is complex, primarily as a selective adhesion molecule inhibitor and a monoclonal antibody.

Quick Summary

Natalizumab is a humanized monoclonal antibody and selective integrin blocker that inhibits immune cell migration. It is classified as an immunomodulator and immunosuppressant used to treat multiple sclerosis and Crohn's disease.

Key Points

Monoclonal Antibody: A humanized IgG4 antibody produced using recombinant technology.
Integrin Antagonist: Blocks the alpha-4 integrin subunit, preventing immune cells from crossing into inflamed tissues.
Immunomodulator: A functional class indicating its ability to modify the immune response.
Selective Immunosuppressant: Suppresses specific parts of the immune system to treat conditions like MS and Crohn's disease.

Primary Classification: Monoclonal Antibody

Natalizumab is classified as a humanized monoclonal antibody (mAb). This means it is a lab-created protein mimicking human antibodies to target specific substances in the body. Being 'humanized' minimizes the risk of rejection by the human immune system. Monoclonal antibodies are a type of biologic drug derived from living organisms.

How monoclonal antibodies work

Monoclonal antibodies are designed to bind to a specific target. Natalizumab targets the alpha-4 integrin subunit found on most white blood cells, interfering with immune cell movement.

Functional Classification: Integrin Antagonist

Natalizumab is also classified as an integrin antagonist or blocker. Integrins are proteins vital for immune cells to adhere to and pass through blood vessel walls to inflamed areas.

The mechanism of action

Natalizumab binds to alpha-4 integrins ($\alpha_4\beta_1$ and $\alpha_4\beta_7$), preventing them from interacting with receptors like VCAM-1 on blood vessels. This action stops activated immune cells from entering the brain in MS and inflamed gut tissue in Crohn's disease, thereby reducing inflammation.

Therapeutic Class: Immunomodulator and Selective Immunosuppressant

Therapeutically, natalizumab is an immunomodulator and selective immunosuppressant. It doesn't broadly suppress the immune system but selectively interferes with immune cell trafficking, a characteristic of newer therapies.

Applications in autoimmune diseases

Natalizumab treats relapsing multiple sclerosis and moderately to severely active Crohn's disease. In MS, it reduces relapses and disability progression by blocking immune cells in the central nervous system. For more detailed information on natalizumab, including comparisons to other treatments and key safety considerations like the risk of PML and the TOUCH® Prescribing Program, please refer to {Link: ScienceDirect Topics https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/natalizumab} and other official resources like the FDA.

Frequently Asked Questions

Natalizumab is a type of biologic drug known as a humanized monoclonal antibody. It is also functionally classified as a selective integrin antagonist and therapeutically as an immunomodulator and selective immunosuppressant.

Natalizumab acts as a selective immunosuppressant by preventing certain inflammatory immune cells from migrating out of the bloodstream and into specific organs, such as the brain and gut. It does this by blocking a protein called alpha-4 integrin on the surface of these immune cells.

As a monoclonal antibody, natalizumab is a highly targeted biologic therapy. Unlike older, less specific drugs, it is engineered to precisely bind to a single target (alpha-4 integrin), which allows it to have a more specific therapeutic effect on the immune system's trafficking.

The most significant risk is Progressive Multifocal Leukoencephalopathy (PML), a rare but serious brain infection caused by the John Cunningham virus (JCV). Risk factors for PML include anti-JCV antibody status, duration of therapy, and prior use of immunosuppressants.

Natalizumab was voluntarily withdrawn in 2005 after cases of PML were identified in clinical trials. It was later reintroduced in 2006 under a strict Risk Evaluation and Mitigation Strategy (REMS) to manage the risk of PML.

The TOUCH® Prescribing Program is a mandatory safety program (REMS) in the U.S. designed to ensure that patients receiving natalizumab are monitored for signs and symptoms of PML and other serious opportunistic infections.

The concurrent use of natalizumab with other immunosuppressants is contraindicated due to an increased risk of serious infections, including PML.

Natalizumab is typically prescribed for adult patients with highly active relapsing forms of multiple sclerosis or moderately to severely active Crohn's disease who have not responded adequately to other therapies.