What is the Optimal Therapy for Crohn's Disease: Step-up or Top-down?

Ming Valerie Lin; Wojciech Blonski; Gary R Lichtenstein


Expert Rev Gastroenterol Hepatol. 2010;4(2):167-180. 

In This Article

Expert Commentary: The Current & Future Therapeutic Paradigms in CD

Under the current therapeutic paradigm, low-risk disease progression is defined as patients with mild presentation, inflammatory disease, absence of perianal disease or extraintestinal manifestations and nonsmokers. Treatment is selected according to the disease location. In colonic CD, treatment is initiated with a 5-ASA agent with or without antibiotics. If the patient responds, 5-ASA agents should be continued with follow-up visits. If the patient does not respond, or if the patient has small intestine involvement, then budesonide or prednisone is the next step-up in treatment. If the patient responds to budesonide or prednisone, it is crucial that the dose is tapered with follow-up visits. If the patient does not respond, then immunomodulators (AZA, 6-MP or methotrexate) should be used. Patients should also be evaluated for the need of surgery. If a patient relapses or remains nonrespondant, then anti-TNF-α should be used. Intermittent-to-high risk progression is defined as patients with a young age at onset (≤18 years), noninflammatory disease behavior, extensive diseases involving small and large bowels, early steroid use, extraintestinal manifestations and those who are active smokers. These patients are initially treated with budesonide or prednisone with immunomodulators (AZA, 6-MP or methotrexate). If a patient shows a response, corticosteroids should be tapered and stopped while continuing on the immunosuppressants. If there is no response, then the patient should be started with an anti-TNF-α agent. If the patient responds to an anti-TNF-α agent, maintenance therapy should be continued. If there is no response, they should be switched to another anti-TNF-α agent (although the data for primary nonresponders are very limited) or natalizumab and surgery may be considered.

The current treatment pyramid uses a step-up approach with conservative use of immunomodulators and biological agents aiming to induce remission, maintain remission, prevent complications, optimize surgical outcomes and improve quality of life. In the future, we hope to invert the treatment pyramid with a top-down approach and earlier use of immunomodulators and biological agents, with additional goals of disease modification, mucosal healing, reduced pharmacoeconomics, disease prevention and improved quality-of-life in selected target populations of those patients who are most at risk for poor outcomes in the absence of aggressive therapy.


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