title: Early administration of azathioprine vs conventional management of Crohn's Disease: a randomized controlled trial.
abstract: OBJECTIVE
  Immunomodulator therapy is effective for patients with Crohn's disease (CD) but has not been shown to affect disease progression, presumably because it is given too late after diagnosis. We compared the efficacy of early treatment (within 6 months after diagnosis) with azathioprine versus conventional management of patients at high risk for disabling disease.
  
  
  METHODS
  We performed an open-label trial of adults with a diagnosis of CD for less than 6 months who were at risk for disabling disease. From July 2005 to November 2010, patients at 24 French centers were randomly assigned to treatment with azathioprine (2.5 mg ∙ kg(-1) ∙ day(-1), n = 65) or conventional management (azathioprine only in cases of corticosteroid dependency, chronic active disease with frequent flares, poor response to corticosteroids, or development of severe perianal disease) (n = 67). The primary end point was the proportion of trimesters spent in corticosteroid-free and anti-tumor necrosis factor (TNF)-free remission during the first 3 years after inclusion.
  
  
  RESULTS
  During the 3-year follow-up period, 16 patients in the azathioprine group were switched to mercaptopurine or methotrexate therapy because of intolerance or poor efficacy. Forty-one patients in the conventional management group required immunosuppressant therapy (61%; median time to first prescription, 11 months). In the azathioprine group, a median 67% of trimesters were spent in remission (interquartile range, 11%-85%) compared with 56% in the conventional management group (interquartile range, 29%-73%) (P = .69). Among secondary outcomes, a higher cumulative proportion of patients in the azathioprine group were free of perianal surgery than in the conventional management group (96% ± 3% and 82% ± 6% at month 36, respectively; P = .036). The cumulative proportion of patients free of intestinal surgery and anti-TNF therapy did not differ between groups.
  
  
  CONCLUSIONS
  Based on results from a clinical trial, administration of azathioprine within 6 months of diagnosis of CD was no more effective than conventional management in increasing time of clinical remission. Clinicaltrials.gov, Number NCT00546546.
authors: Hôpital St-Antoine and Université Pierre et Marie Curie, Paris, France. Electronic address: jacques.cosnes@sat.aphp.fr.
authors: Jacques
authors: J
authors: Cosnes
authors: Anne
authors: A
authors: Bourrier
authors: David
authors: D
authors: Laharie
authors: Stéphane
authors: S
authors: Nahon
authors: Yoram
authors: Y
authors: Bouhnik
authors: Franck
authors: F
authors: Carbonnel
authors: Matthieu
authors: M
authors: Allez
authors: Jean-Louis
authors: JL
authors: Dupas
authors: Jean-Marie
authors: JM
authors: Reimund
authors: Guillaume
authors: G
authors: Savoye
authors: Pauline
authors: P
authors: Jouet
authors: Jacques
authors: J
authors: Moreau
authors: Jean-Yves
authors: JY
authors: Mary
authors: Jean-Frédéric
authors: JF
authors: Colombel
mesh_terms: D000328:Adult; D001379:Azathioprine / Q000009:adverse effects / Q000627:therapeutic use*; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D001379:Azathioprine
keywords: CD; CDAI; Comparison of Treatment Strategies; Crohn’s Disease Activity Index; Crohn’s disease; Drug; IBD; IBDQ; IQR; Inflammatory Bowel Disease; Inflammatory Bowel Disease Questionnaire; TNF; interquartile range; tumor necrosis factor