What type of drug is natalizumab? Understanding its class and function

October 8, 2025 •

3 min read

Over 2.8 million people worldwide live with multiple sclerosis, and natalizumab (Tysabri) is a powerful, targeted treatment option for relapsing forms of the disease. What type of drug is natalizumab? It is a specialized monoclonal antibody that acts as a selective immunosuppressant.

Quick Summary

Natalizumab is a monoclonal antibody and selective immunosuppressant that functions as an integrin receptor antagonist. It treats relapsing multiple sclerosis and Crohn's disease by blocking inflammatory immune cells from entering the central nervous system or gut.

Key Points

Drug Class: Natalizumab is a monoclonal antibody and selective immunosuppressant classified as an integrin receptor antagonist.
Mechanism of Action: It blocks the alpha-4 (α4) integrin on immune cells, stopping their migration into inflamed tissues.
Approved Uses: Treats relapsing forms of multiple sclerosis (MS) and moderately to severely active Crohn's disease.
Major Risk: Significant risk of Progressive Multifocal Leukoencephalopathy (PML), a rare brain infection from the JC virus.
Restricted Access: Available only through REMS programs like TOUCH due to the PML risk.
Administration: Given as an intravenous infusion approximately every four weeks.
Brand Names: Marketed as Tysabri, with a biosimilar called Tyruko.

Natalizumab is a potent biologic medication classified as a monoclonal antibody and a selective immunosuppressant. More specifically, it is an integrin receptor antagonist. Marketed as Tysabri and its biosimilar Tyruko®, natalizumab manages certain autoimmune disorders by controlling immune cell migration. While effective, it carries significant safety considerations, particularly the risk of Progressive Multifocal Leukoencephalopathy (PML).

The Function of Natalizumab as a Monoclonal Antibody

As a humanized monoclonal antibody, natalizumab is a lab-created protein designed to mimic natural antibodies. It targets a specific protein on immune cells, interfering with the inflammatory process in conditions driven by misdirected immune activity.

How Natalizumab's Unique Mechanism Works

Natalizumab prevents immune cells (leukocytes) from entering organs like the brain, spinal cord, and gut. It binds to the alpha-4 (α4) integrin subunit on immune cells, which normally helps them cross blood vessel walls into tissues. By blocking α4 integrin, natalizumab inhibits this migration, interfering with interactions like α4β1 and α4β7 with VCAM-1 and MAdCAM-1. In MS, this stops inflammatory T cells from entering the central nervous system; in Crohn's disease, it blocks immune cells from the digestive tract.

Approved Medical Uses

Natalizumab is approved for relapsing forms of Multiple Sclerosis (MS), including CIS, RRMS, and active SPMS, to slow disability and reduce relapses. It is also used for moderately to severely active Crohn's Disease (CD) in adults who haven't responded to or tolerated other treatments.

Safety Profile and Significant Risks

Progressive Multifocal Leukoencephalopathy (PML)

The main safety risk is PML, a rare, life-threatening brain infection from the JC virus. Risk factors include positive anti-JCV antibody status, longer treatment duration (especially after two years), and prior immunosuppressant use. Due to this risk, natalizumab is available only through restricted distribution programs like the TOUCH® Prescribing Program.

Other Potential Risks

Other serious adverse effects include hypersensitivity reactions, liver damage, herpes infections, and low platelet counts.

Comparing Natalizumab to Other Treatments


Feature	Natalizumab (Tysabri)	Interferon Beta (e.g., Avonex)	Vedolizumab (Entyvio)
Drug Class	Monoclonal Antibody / Integrin Receptor Antagonist	Immunomodulator (Biologic)	Monoclonal Antibody / Integrin Receptor Antagonist
Mechanism of Action	Blocks α4 integrin, preventing immune cell migration into the brain, spinal cord, and gut	Modifies immune response to reduce inflammation, though the exact mechanism isn't fully defined	Blocks α4β7 integrin, primarily inhibiting immune cell migration into the gut
Administration	Intravenous infusion every 4 weeks	Intramuscular or subcutaneous injections (frequency varies, e.g., weekly)	Intravenous infusion every 8 weeks (after initial doses)
Major Risk	Progressive Multifocal Leukoencephalopathy (PML)	Flu-like symptoms, injection site reactions, potential liver toxicity	Infusion reactions, infections; lower systemic exposure results in lower PML risk compared to natalizumab
Primary Use	Relapsing MS and moderate-to-severe Crohn's Disease	Relapsing forms of MS	Moderate-to-severe Crohn's Disease and ulcerative colitis

Conclusion

Natalizumab (Tysabri) is an advanced monoclonal antibody and selective integrin antagonist used for relapsing MS and certain Crohn's disease cases. Its mechanism effectively controls disease by preventing inflammatory cell migration. However, this benefit is balanced by the rare but serious risk of PML, requiring participation in a strict risk mitigation program like TOUCH. Regular monitoring for the JC virus is crucial. The decision to use natalizumab involves weighing its efficacy against its risks in consultation with a healthcare provider. More details on the risk management program can be found on the {Link: TOUCH On-Line website https://www.touchprogram.com/TTP/}.

Frequently Asked Questions

The most significant risk is Progressive Multifocal Leukoencephalopathy (PML), a rare, serious viral brain infection caused by the JC virus that can lead to severe disability or death.

The risk of developing PML increases with the duration of therapy, especially after two years, and is linked to anti-JCV antibody status and prior immunosuppressant use.

Yes, it is a selective immunosuppressant that prevents specific immune cells from entering inflamed areas, reducing inflammation without broadly suppressing the immune system.

TOUCH is an FDA-required REMS program to manage the PML risk, ensuring proper prescribing, administration, and monitoring by registered providers and centers.

It is indicated for adult patients with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.

It is approved for adult patients with moderately to severely active Crohn's disease unresponsive to other treatments like TNF-alpha inhibitors.

It is given as a one-hour intravenous infusion, usually every four weeks, with post-infusion monitoring at the center.

Yes, natalizumab-sztn (Tyruko) is an FDA-approved biosimilar.