Top-down therapy: is the evidence strong enough?

Crohn's disease (CD) has usually been managed in an escalation manner, introducing more powerful (and toxic) drugs only once those with a better safety profile had failed. However, the natural history of CD under conventional therapeutic strategies results in high intestinal resection requirements and high rates of clinical relapse and steroid dependence. Indirect data seem to point at an improved efficacy of drugs when they are introduced early after disease diagnosis. The spreading use of immunomodulators and the appearance of biological agents prompted the idea of their early introduction in order to change the natural history of the disease. By now, only thiopurines have been shown to reduce steroid requirements, relapse rates, and even surgical requirements, at least in pediatric CD. However, many other 'top-down' treatment strategies have not yet been evaluated. In addition, there is a risk of overtreating those 10-30% of patients that will have a benign course of the disease; that's the reason why the implementation of top-down strategies remains as a matter of debate.