A critical assessment of new therapies in inflammatory bowel disease

The only therapy in inflammatory bowel disease (IBD), which up to the mid-1990s was disease modifying, was immunosuppression with azathioprine. Other 'standard' therapies in IBD were merely symptomatic. With the advent of biological therapies, especially the chimeric monoclonal anti-TNF antibody infliximab, we start to target specific pathogenic disease mechanisms, which allow thorough suppression of the disease process and healing of the bowel in the long term. Moreover, infliximab is the only drug up to the present that allows short-term healing of fistulizing Crohn's disease. This therapy is, however, associated with problems of immunogenicity. The formation of antibodies to infliximab jeopardizes the efficacy and is associated with infusion reactions. Optimization of anti-TNF strategies will occur in the coming years. Another promising therapy is antagonization of alpha4 integrins and hence, of migration of inflammatory cells to the intestine. It can be expected that more simple therapies using small molecules that inhibit the key cytokines or pro-inflammatory processes will take over in the next decade. In the current and future approach to IBD therapy immunosuppression with azathioprine or 6-MP and methotrexate play a central role. At the present time, the combination of infliximab with azathioprine or methotrexate can be regarded as the new standard for the therapy of refractory Crohn's disease. In ulcerative colitis (UC) much less progress has been made and the value of biological therapy as well as of long-term management with immunosuppression remains controversial. Probiotics are an attractive treatment option for IBD but studies so far are small and data are not yet convincing.