New biotechnological therapies for Crohn's disease: where are we now?
Recent advances in mucosal immunology have provoked recent interest in the application of biodrugs to Crohn's disease intestinal inflammation. Our understanding of the roles of cytokines, adhesion molecules, cell trafficking and cellular immune mechanisms of disease has lead to a number of recent clinical trials. There has been simultaneous research by a number of groups using several animal models of gut inflammation. Better animal models and in particular, the use of gene knock-outs and transgenics has benefitted our understanding of the inflammatory components of Crohn's. Examples of early cellular biodrugs included anti-CD4 monoclonal antibodies. The recent FDA approval of infliximab was preceded by knowledge that levels of tumour necrosis factor (TNF)-alpha are suppressed in the clinical therapy of Crohn's. A recent study of interleukin (IL)-10 was not as favourably reported. Equivocal data has not supported the use of IL-10 for Crohn's disease therapy at this time. An ongoing multicentre phase III study of antisense to ICAM-1 for Crohn's disease is nearing completion and review. The newer monoclonal antibodies to enter into clinical studies of Crohn's disease therapy include those targeting the adhesion molecules beta7 and alpha4beta7. Numerous other biodrugs are in planning stages or early clinical studies. The coagulation pathway is another target that has been identified. This range of compounds will produce mixed efficacy in clinical studies and winners and losers will result. Moreover, combination therapy using 2 or more of these and other pre-existing compounds may prove clinically beneficial. Tailoring of pharmaceutical use to specific patients may also be expected, as we understand more about the subclasses of Crohn's disease.
Yacyshyn
B R
BR
University of Alberta, Edmonton, Alberta, Canada. bruce.yacyshyn@ualberta.ca