Biological Therapies in Inflammatory Bowel Disease: Top-down or Bottom-up?

Bas Oldenburg; Daan Hommes


Curr Opin Gastroenterol. 2007;23(4):395-399. 

In This Article

Abstract and Introduction

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.

Since inflammatory bowel disease (IBD) cannot be cured, the ultimate goal of treatment is focused on maintaining the highest achievable quality of life. Thus, medication ought to be tailored to the individual patient with a well balanced drug benefit/side effect ratio. In the recently published European Crohn's and Colitis Organization (ECCO) consensus, a sequential or step-up therapy was advocated in patients with Crohn's disease.[1**] Depending on activity site, severity of disease and complications, the consecutive or combined use of sulfasalazine, budenoside, systemic steroids, immunosuppressive drugs and infliximab was recommended by a panel of European IBD specialists. Infliximab is generally recommended in Crohn's disease patients who are refractory or intolerant to conventional drugs and represents the peak of the therapeutic pyramid.[1**,2,3] In ulcerative colitis infliximab is effective in moderate to severe disease,[4] but could also be used in patients who have failed to respond to high-dose corticosteroids as a rescue therapy.[5] Evidence that the sequential strategy is superior to others, however, is not available. Recently, a conceptually attractive new approach has been presented in the literature; that is, the 'top-down' regimen. In this review the potential benefits and disadvantages of this approach will be critically appraised.


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