Clinical, Biological, and Laboratory Parameters as Predictors of Severity of Clinical Outcome and Response to Anti–TNF–Alpha Treatment in Ulcerative Colitis

Ulcerative colitis (UC) is a chronic relapsing inflammatory bowel disease (IBD). The pathogenesis of IBD is complex and so far not fully understood. The long-term clinical outcome of UC is hard to predict. Some clinical phenotypes of UC may to some extent predict the severity of the disease, but the clinical impact of these predictors is minor. . The new immunomolecular understanding of the pathophysiological mechanisms behind the disease, and especially the genetic engineering knock out animal models in early 1990’s, was the start of a new therapeutic strategy: the targeting therapy. Based on new knowledge of proinflammatory and anti-inflammatory molecules, new therapeutic targets were established to attack specific components of the inflammatory cascade. TNF-alpha was the first molecule to be blocked with effects on the disease activity first described in the animal models and then described in humans in 1995 for Crohns disease (CD). Later on, numerous other targeting molecules have been developed with more or less efficacy. So far the anti-TNF agent infliximab (IFX) is the only targeting agent that has been found to be effective in UC. However, a lot still needs to be done in order to achieve “personalized engineered therapy” in IBD. After some ten years experiences with targeting therapy the major unresolved questions are: which UC patients will have the greatest effect of targeting therapy inducing a “deep, longstanding“ remission and prevent severe outcome such as colectomy? Which patients are in the need of long-term maintenance therapy? If and when can target therapy be stopped? Few studies have investigated potential predictors of the disease’s severity and future clinical outcome after the introduction of targeting therapy. Therefore, after ten years with targeting therapy of UC, what clinical, biological or histological markers could give some answers to these questions addressed above?