Top-down therapy for Crohn's disease: rationale and evidence.

Several trials have shown that early treatment of Crohn's disease with immunomodulators and anti-TNF agents leads to superior clinical outcome including healing of the mucosa. Evidence is mounting that this endpoint is associated with a reduced risk of complications and a reduced need for surgeries and hospitalizations. In the SONIC trial, treatment with the combination of azathioprine and infliximab was the most potent anti-inflammatory therapy in Crohn's disease patients with evidence of active inflammation who had never been exposed to immunomodulators or biologics. These findings have introduced a trend towards earlier initiation of immunomodulator therapy, comparable to what is being done in rheumatoid arthritis. Given the fact that subsets of patients have a favorable disease course without immunomodulator therapy and given the significant potential toxicity of these medications, however, it is becoming a challenge to the gastroenterologists to try and identify patients with an unfavorable disease prognosis and treat these early and aggressively. The key to successful management of Crohn's disease appears to lie in careful timing and selection of the appropriate interventions.