Biological therapies in inflammatory bowel disease: present and future

Although the cause of inflammatory bowel disease (IBD) remains completely unknown, pathogenic mechanisms have gradually been unraveled. Crohn's disease (CD) is believed to result from a T helper (Th) 1-mediated response in the bowel wall, whereas mucosal inflammation in ulcerative colitis seems to be Th 2 orientated. Immunomodulation therapies in CD, therefore, have mainly targeted the initial step in the antigen-triggered immune activation. Tumour necrosis factor (TNF) plays a key role in this process and anti-TNF strategies have been extensively evaluated. Treatment with chimeric monoclonal antibodies to TNF (infliximab) are now extensively used in the clinic. Another approach is inhibition of migration of inflammatory cells, including the use of antibodies to alpha4 integrin (natalizumab), which hold great promise and might present a more specific approach to IBD-related inflammation than the overall effect of TNF, which is also a key cytokine for normal defense mechanisms. The present data on biological therapies seem to indicate that these therapies should always be used in combination with immunosuppression therapy. However, the long-term safety of biological therapies still needs to be monitored.