Anti-integrin therapy in inflammatory bowel disease Domina Petric, MD

Integrins Integrins are a family of adhesion molecules on the surface of leukocytes. They may interact with another class of adhesion molecules on the surface of the vascular endothelium: selectins. Circulating leukocytes adhere to the vascular endothelium and move through the vessel wall into the tissue by interaction between integrins and selectins.

Natalizumab Natalizumab is a humanized IgG4 monoclonal antibody targeted against the α4 subunit. It blocks several integrins on circulating inflammatory cells. It prevents binding to the vascular adhesion molecules and subsequent migration into the surrounding tissues.

Natalizumab It has shown significant efficacy for a subset of patients with moderate to severe Crohn´s disease. In clinical trials 3 of 3100 patients developed progressive multifocal leukoencephalopathy due to reactivation of a human polyomavirus (JC virus). JC virus is present in latent form in over 80% of adults.

Natalizumab Despite that, FDA approved natalizumab for the treatment of patients with moderate to severe disease, who have failed other therapies, through a carefully restricted program. Dosage is 300 mg every 4 weeks by intravenous infusion. Patients should not be on other immune suppressant agents!

Natalizumab Approximately 50% of patients respond to initial therapy with natalizumab. Long-term response is maintained in 60% and remission in over 40%. Other adverse effects are acute infusion reactions and a small risk of opportunistic infections.

Katzung, Masters, Trevor. Basic and clinical pharmacology. Literature Katzung, Masters, Trevor. Basic and clinical pharmacology.