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Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. May 7, 2008; 14(17): 2670-2677
Published online May 7, 2008. doi: 10.3748/wjg.14.2670
Controversies in the treatment of Crohn’s disease: The case for an accelerated step-up treatment approach
Amandeep K Shergill, Jonathan P Terdiman
Amandeep K Shergill, Veterans Affairs Medical Center, Division of Gastroenterology, University of California, San Francisco 94143, United States
Jonathan P Terdiman, Division of Gastroenterology, University of California, San Francisco 94143, United States
Author contributions: Shergill AK and Terdiman JP contributed equally to this work; both Shergill AK and Terdiman JP researched and wrote the paper.
Correspondence to: Jonathan P Terdiman, MD, Division of Gastroenterology, University of California, San Francisco, Box 1623, San Francisco 94143, United States.
Telephone: +1-415-3537906
Fax: +1-415-5022249
Received: December 19, 2007
Revised: January 31, 2008
Published online: May 7, 2008

The ideal treatment strategy for Crohn’s disease (CD) remains uncertain, as does the optimal endpoint of therapy. Top-down versus step-up describes two different approaches: early use of immunomodulators and biological agents in the former versus initial treatment with steroids in the latter, with escalation to immunomodulators or biological drugs in patients proven to be steroid refractory or steroid dependent. Top-down therapy has been associated with higher rates of mucosal healing. If mucosal healing proves to be associated with better long-term outcomes, such as a decreased need for hospitalization and surgery, top-down therapy may be the better approach for many patients. The main concern with the top-down approach is the toxicity of the immunomodulators and biological agents, which have been linked with infectious complications as well as an increased risk of lymphoma. It is unlikely that one strategy will be best for all patients given the underlying heterogeneity of CD presentation and severity. Ultimately, we must weigh the safety and efficacy of the therapies with the risks of the disease itself. Unfortunately our ability to risk stratify patients at diagnosis remains rudimentary. The purpose of this paper is to review the data that supports or refutes the differing treatment paradigms in CD, and to provide a rationale for an approach, termed the “accelerated step-up” approach, which attempts to balance the risks and benefits of our currently available therapies with the risk of disease related complications as we understand them in 2008.

Keywords: Crohn’s disease, Top-down, Step-up, Anti-tumor necrosis factor antibodies, Immunomodulators, Mucosal healing