Four controlled trials met the inclusion criteria (n=433) and compared azathioprine (n=151) or 6-mercaptopurine (n=47) with control arms (placebo with or without antibiotic induction therapy or mesalamine, n=235). Study quality was scored at least 3 in all studies. Factors that affected bias, adequate sequence generation, blinding and incomplete outcome data were addressed in three studies and allocation concealment in two. Study duration ranged from 12 to 24 months.
Compared with controls, purine analogues were significantly more effective in preventing clinical recurrence at one year (RR 8%, 95% CI 1 to 15; four studies; NNT=13) and two years (RR 13%, 95% CI 2 to 24; two studies; NNT=8) and for preventing severe endoscopic recurrence (RR 15%, 95% CI 1.8 to 29; three studies; NNT=7), but they were not effective in the prevention of very severe endoscopic recurrence. The rate of adverse events leading to drug withdrawal was higher in patients treated with purine analogues than for controls (17.2% versus 9.8%; p=0.021).
In the sensitivity analyses, efficacy of purine analogues at one year was superior to that of placebo for the prevention of both clinical (RR 13%, 95% CI 1.8 to 25, p=0.025; NNT=7) and endoscopic recurrence (RR 23%, 95% CI 9 to 37; NNT=4).
Publication bias was assessed and found to be absent.