Integrin-based therapeutics: biological basis, clinical use and new drugs

Key Points Integrin antagonists are highly successful drugs for targeting the ligand binding site of αIIbβ3, α4-containing or α4β7 integrins. Antagonists to αIIbβ3 integrin are still being used in patients receiving percutaneous angioplasty but are being replaced in many instances by new classes of anticoagulants and platelet inhibitors. Natalizumab, a monoclonal antibody against α4-containing integrins, is highly successful at treating multiple sclerosis, but can reactivate John Cunningham virus and cause lethal progressive multifocal leukoencephalopathy (PML). Vedolizumab, a monoclonal antibody against α4β7 integrin, and new antibodies against the β7 integrin subunit have not shown any signs of inducing PML. Vedolizumab is safe and effective in the treatment of inflammatory bowel disease and has effectively replaced natalizumab for the treatment of Crohn disease.