Randomized controlled azathioprine withdrawal after more than two years treatment in Crohn's disease: increased relapse rate the following year

Aliment Pharmacol Ther. 2004 Jun 1;19(11):1147-52. doi: 10.1111/j.1365-2036.2004.01944.x.


Introduction: Azathioprine is effective for maintenance of remission in Crohn's disease, however, duration of efficacy and the dose response relationship has not been fully evaluated.

Aims: To investigate whether patients kept in remission by azathioprine treatment for >2 years benefit from further treatment, and to explore dose-response relationship.

Patients and methods: In an open 12-month trial, patients with inactive Crohn's disease after >2 years (median 37 months) of azathioprine treatment were randomized to azathioprine withdrawal or continued treatment. Primary end point was relapse defined as: (i) Crohn's disease activity index rise >/= 75, and Crohn's disease activity index >150 or (ii) disease activity requiring intervention.

Results: Of 29 patients, 28 completed the observation period or relapsed. Eleven of 13 patients (85%) continuing azathioprine remained in remission compared with seven of 15 (47%) observed without azathioprine (P = 0.043). In patients who had been treated with azathioprine >1.60 mg/kg/day the difference was even more pronounced, eight of nine (89%) vs. four of 12 (33%) respectively (P = 0.017).

Conclusions: Patients with Crohn's disease in remission after >2 years of continuous azathioprine treatment will benefit from further continued treatment. Further controlled studies with azathioprine doses <2.0 mg/kg/day are needed.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Azathioprine / administration & dosage*
  • Crohn Disease / drug therapy*
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Humans
  • Immunosuppressive Agents / administration & dosage*
  • Middle Aged
  • Recurrence


  • Immunosuppressive Agents
  • Azathioprine