Altering the natural history of Crohn's disease?

With the medical advances achieved in Crohn's disease (CD) over the past several years, treatment goals have expanded to include not only improvement in clinical outcomes, but also potential alteration of underlying disease processes and modification of the clinical course. A reliable prospective predictive model for the clinical course of CD is presently lacking. However, preliminary evidence suggests that the clinical expression of CD may reflect at least in part transmural and superficial mucosal inflammatory changes. Treatments that induce healing of the intestinal mucosa and submucosa may therefore provide particular clinical benefits, including sustained response or remission. As a result, endoscopic outcomes in patients with CD are increasingly included as therapeutic efficacy end points in clinical studies. Corticosteroids have been shown to rapidly relieve symptoms in most patients but generally do not improve endoscopic lesions in parallel with clinical response and are ineffective as maintenance therapy. Open-label investigations suggest that azathioprine is associated with mucosal healing; in addition, placebo-controlled studies have demonstrated that this immunosuppressive agent can provide long-term suppression of disease activity, although initial onset of clinical action is slow. The antitumor necrosis factor-alpha monoclonal antibody infliximab provides endoscopic healing in parallel with clinical improvement and also effectively maintains remission with retreatment. As the relationship between endoscopic and clinical changes in disease activity is further explored and clarified, new treatment strategies will need to be developed to improve long-term prognosis in patients with CD.