Targeted therapies in inflammatory bowel disease.
The pathogenesis of inflammatory bowel disease (IBD) is still not completely understood, however the ongoing research of the last decade is allowing the hypothesis that in genetically predisposed individuals distinct environmental factors result in a dysregulation of the mucosal immune system and thus IBD. Until today the majority of patients are being treated with rather unspecific medications exerting suppressive effects on the mucosal immune system. Nevertheless, theses substances including azathioprine and steroids have proven excellent efficacy for defined subgroups of patients. However, the better understanding of the underlying pathogenesis resulted in the clinical development of novel therapeutic strategies with specific targets. The most prominent example being antibodies targeting tumor necrosis factor-alpha which are routinely administered in patients suffering from either Crohn's disease (CD) or ulcerative colitis. A second strategy is targeting the protein subunit p40 which heterodimerizes either with p35 resulting in the pro-inflammatory cytokine IL-12 or with p19 thus forming the pro-inflammatory IL-23. Experimental data suggest a crucial role for both cytokines in experimental colitis. Various antibodies against p40 are currently in clinical trials for patients with CD. In areas of inflammation, the blood vessel endothelial cells upregulate adhesion molecules resulting in the infiltration of leukocytes into the respective area. Natalizumab blocks these adhesion molecules. Treatment with natalizumab was associated with clinical improvement in patients with CD and has been approved in the USA. In summary, several therapeutic targets have already entered our clinical routine and have for some patients resulted in significant changes of the disease course.
Siegmund
Britta
B
Charité, Campus Benjamin Franklin, Medizinische Klinik I, Berlin, Germany. britta.siegmund@charite.de
D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000628:therapy*; D057170:Translational Research, Biomedical