Biological therapies in inflammatory bowel disease: top-down or bottom-up?

PURPOSE OF REVIEW

Conventional therapeutic algorithms cannot, or only to a certain degree, prevent surgery or complications in inflammatory bowel disease. The new concept of early aggressive or 'top-down' treatment has evolved from the impressive results of new biological agents in the treatment of patients who were refractory to standard therapy. New data, suggesting that this strategy may be advantageous, has recently been published.

RECENT FINDINGS

In uncontrolled studies, early administration of azathioprine as well as infliximab has been shown to be associated with a prolonged maintenance of remission in Crohn's disease patients. The recently presented preliminary data from a controlled study comparing early administration of infliximab and azathioprine ('top-down' therapy) versus conventional 'step-up' therapy showed superior mucosal healing, a more rapid remission and higher remission rates in patients in the top-down treatment arm. The ongoing SONIC study, which compares infliximab therapy with and without azathioprine, will provide additional information regarding the relative importance of both drugs in this respect.

SUMMARY

The significance of top-down treatment remains to be confirmed in prospective clinical studies aimed at high-risk patients. The standard use of this approach cannot be advocated presently.