natalizumab

Natalizumab is a humanized monoclonal antibody that binds alpha-4 integrin (VLA-4) on the surface of activated leukocytes. By blocking the interaction of VLA-4 with its ligands, VCAM-1 and fibronectin, natalizumab prevents leukocyte adhesion and migration across endothelium into the central nervous system and the gut, reducing inflammatory activity in autoimmune diseases.

Medical use

It is approved for relapsing forms of multiple sclerosis to reduce clinical relapses and the rate of disability progression, and for adults with moderate to severe Crohn’s disease when other therapies have failed or are not tolerated. Efficacy is demonstrated by reductions in relapse frequency and radiographic or clinical signs of disease activity.

Administration and formulation

Natalizumab is given by intravenous infusion at a dose of 300 mg every four weeks. It is typically prescribed under a risk management program due to potential safety concerns and requires regular monitoring.

Safety and monitoring

The principal safety concern is progressive multifocal leukoencephalopathy (PML), a rare but potentially fatal brain infection associated with JC virus. Risk factors include JC virus serostatus (positive), prior immunosuppressant use, and duration of therapy, with risk increasing over time. Other potential adverse effects include infusion reactions, liver injury, infections, and hypersensitivity. Because of PML risk, treatment is accompanied by JC virus antibody testing and periodic MRI surveillance. Pregnancy and use in special populations require careful consideration and counseling.

History

Natalizumab was approved for MS in 2004, temporarily withdrawn in 2005 after PML cases, and reintroduced in 2006 with a restricted risk management program. It has since been approved for Crohn’s disease in appropriate patients. Brand name commonly cited is Tysabri.