Strategies for targeting tumour necrosis factor in IBD.

Tumour necrosis factor (TNF) plays an important role in mediating the inflammation of inflammatory bowel disease, in particular, Crohn's disease. Strategies aimed at reducing tumour necrosis factor in patients with inflammatory bowel disease include the mouse/human chimeric monoclonal antibody infliximab, the humanized monoclonal antibody CDP571, the human soluble TNF p55 receptor onercept, the human monoclonal antibody D2E7 (adalimumab), the anti-TNF human antibody Fab' fragment-polyethelene glycol (PEG) conjugate CDP870, and the small molecules thalidomide and CNI-1493 (MAP-kinase inhibitor). Infliximab is effective for treating active Crohn's disease, maintaining remission, closing fistulas, maintaining fistula closure, and treating ankylosing spondylitis. Infliximab is also being investigated for the treatment of ulcerative colitis. Side-effects occurring in patients treated with infliximab include human anti-chimeric antibodies, infusion reactions, delayed hypersensitivity reactions, formation of autoantibodies, and, in rare circumstances, drug-induced lupus and serious infections, including tuberculosis. CDP571 is effective for treating active Crohn's disease, steroid sparing, and possibly for closing fistulas and maintaining remission. Side-effects occurring in patients treated with CDP571 include anti-idiotype antibodies, infusion reactions and the formation of autoantibodies. A controlled trial of etanercept in patients with Crohn's disease was negative. Pilot studies with onercept, thalidomide, and CNI-1493 have suggested benefit for Crohn's disease. There are no published data on the efficacy of adalimumab (D2E7) or CDP870 for either Crohn's disease or ulcerative colitis. Anti-tumour necrosis factor therapies are effective for the treatment of Crohn's disease and are being investigated for ulcerative colitis.