Current directions of biologic therapies in inflammatory bowel disease.

Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases which can be difficult to control with conventional therapies. A greater understanding of their pathophysiology has led to new therapies that target specific molecules of the inflammatory cascade. Three anti-tumor necrosis factor (TNF) monoclonal antibodies have been developed. Infliximab and adalimumab can induce clinical response and sustained remission in CD. Infliximab is also effective in UC. Certolizumab pegol gives good short-term results but long-term efficacy has yet to be determined in other clinical trials. Therapies that target leucocyte trafficking (anti-integrins) have also been developed and are associated with good clinical response in CD. Natalizumab (anti-α4 integrin antibody) is associated with important side effects and is not used anymore in gastroenterology in Europe but is still used in the USA. Vedolizumab (MLN0002), an anti-α4β7 integrin antibody, has a good efficacy and safety profile. Monoclonal antibodies targeting other cytokines are also under development. For example, ustekinumab (CNTO 1275) inhibits interleukins 12 and 23. It is associated with a good clinical response in CD.