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.