Azathioprine and 6-mercaptopurine for the prevention of postoperative recurrence in Crohn's disease: a meta-analysis.
OBJECTIVE
To evaluate the efficacy and safety of purine analogs (azathioprine, 6-mercaptopurine (6-MP)) in the prevention of postoperative recurrence in Crohn's disease (CD).


METHODS
We searched MEDLINE, the Cochrane Library, and EMBASE. The primary end points, clinical and endoscopic recurrence at 1 and 2 years, and safety were analyzed by the methods of Peto and Der Simonian and Laird.


RESULTS
Four controlled trials enrolled 433 patients and compared azathioprine (n=3) or (6-MP) (n=1) with control arms (placebo with or without antibiotic induction therapy or mesalamine). In the overall analysis, purine analogs were more effective than control arms in preventing clinical recurrence at 1 year (mean difference, 95% confidence interval (CI): 8, 1-15%, P=0.021, number needed to treat (NNT)=13) and 2 years (mean difference, 95% CI: 13%, 2-24%, P=0.018, NNT=8). In sensitivity analyses, the efficacy of purine analogs was superior to that of placebo for the prevention of clinical and endoscopic recurrence at 1 year (mean differences, 95% CI: 13, 1.8-25%, P=0.025, NNT=7, and 23%, 9-37%, P=0.0016, NNT=4, respectively). At 1 year, in the overall analysis, purine analogs were more effective than control arms were in preventing severe (i2-4) endoscopic recurrence (mean difference, CI 95%: 15, 1.8-29%, P=0.026, NNT=7), but they were not effective in the prevention of very severe (i3-4) recurrence. The rate of adverse events leading to drug withdrawal was higher in thiopurine-treated patients than in control arms (17.2 vs. 9.8%, respectively, P=0.021).


CONCLUSIONS
Purine analogs are more effective than placebo in preventing both clinical and endoscopic postoperative recurrence in CD, but they are associated with a higher rate of adverse events leading to drug withdrawal.
Peyrin-Biroulet
Laurent
L
Hôpital Claude Huriez, Centre Hospitalier Universitaire de Lille, Lille 59037, France.
Deltenre
Pierre
P
Ardizzone
Sandro
S
D'Haens
Geert
G
Hanauer
Stephen B
SB
Herfarth
Hans
H
Lémann
Marc
M
Colombel
Jean-Frédéric
JF
D001379:Azathioprine / Q000627:therapeutic use*; D003424:Crohn Disease / Q000517:prevention & control* / Q000601:surgery*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D015122:Mercaptopurine / Q000627:therapeutic use*; D012008:Recurrence
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine