Azathioprine & 6-Mercaptopurine in Crohn Disease

Clinical Question

Is azathioprine efficacious in patients with recurrent flares of Crohn disease in maintaining remission?

Clinical Bottom Lines

  1. Azathioprine and 6-mercaptopurine are both effective agents in the treatment of Crohn disease or in inducing remission.
  2. They exhibit a steroid-sparing effect which is significant for patients with severe, recurring disease requiring long-term therapy.
  3. As with other antimetabolite drugs, these agents need to be judiciously used; adverse effects are more common in treated patients prompting withdrawl of the therapy.

The Evidence

Active Active Quiescent Quiescent Adverse Effects
Therapy Steroid sparing Therapy Steroid sparing
Common Odds ratio (95%CI) 3.09 (2.45-3.91) 3.69 (2.12-6.42) 2.27 (1.76-2.93) 4.64 (1.00-21.54) 5.26 (2.20-12.60)

Comments

  1. Duration of therapy correlated with disease response compared to placebo[<17 weeks, COR 1.25; 17 weeks, COR 1.95; >17 weeks, COR 19.20.]
  2. There was a cumulative dose response during treatment of active disease; as the cumulative dose increased above 200/mg/kg, there was an increase in the odds ratio of 1.32 for each 100 mg/kg increase in dose. Similarly, there was an increase in the odds ratio of 1.19 for each increase of 100 mg/kg dose for quiescent disease.
  3. Despite differences in end-points of the individual studies, particular interest was given to the effect on steroid use, and the authors took this into consideration during the conclusions. There seems to be a steroid-sparing effect that is more strongly substantiated by the results during active therapy, because of the wide confidence interval around the common odds ratio seen in quiescent disease (does NOT exlcude an OR of 1.)
  4. Side-effects COR was greater than the COR for treatment.
  5. This was a meta-analysis of randomized, placebo controlled, blinded studies, the results of which are reliable (based on all measures of validity identified in the JAMA Users' guides to the Medical Literature series) and the conclusions of which can be applied to your patients.

APPRAISED BY: Patrick Sousa, MD

DATE: October 11, 1995

Azathioprine and 6-Mercaptopurine in Crohn Disease; A Meta-Analysis. Pearson, et al. Ann Intern Med. July 1995;122:132-142.