title: Biological therapies in inflammatory bowel disease: top-down or bottom-up?
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastroenterology, University Medical Center Utrecht, The Netherlands. b.oldenburg@umcutrecht.nl
authors.forename: Bas
authors.initials: B
authors.lastname: Oldenburg
authors.forename: Daan
authors.initials: D
authors.lastname: Hommes
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D012074:Remission Induction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha