The future of IBD treatment.

Throughout most of the past 50 years, treatment of Crohn's disease and ulcerative colitis has been dominated by the use of agents whose efficacy was defined on an empiric basis. Many of these, including most especially 5-amino salicylic acid (5-ASA)-based agents and corticosteroids, remain mainstays of current treatment even as research is catching up with clinical experience to define the mechanistic basis of their efficacy. Other agents, also of established utility in at least a subset of patients, were developed on the basis of general inferences about disease pathogenesis. These agents are exemplified by antibiotics (metronidazole) and immunosuppressive agents (azathioprine/6-mercaptopurine, methotrexate, and cyclosporine); attention was directed on the assumption of the general likely importance of microbial species and immunoactivation, respectively. However, the rapid progress, even if still incomplete in understanding of pathophysiological mechanisms that play a role in IBD, has transformed the development of new therapeutic agents, enabling the development of several agents now available or currently in advanced clinical development. It is notable that each of the major overall thrusts in development of new therapeutic strategies parallels, and may be reasonably viewed as the partial outgrowth of, dominant areas of progress in understanding of disease mechanisms relevant to IBD.