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


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


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.
Vilien
M
M
Gastroenterology Department, West Zealand Hospital, Denmark. m.vilien@dadlnet.dk
Dahlerup
J F
JF
Munck
L K
LK
Nørregaard
P
P
Grønbaek
K
K
Fallingborg
J
J
D000328:Adult; D000368:Aged; D001379:Azathioprine / Q000008:administration & dosage*; D003424:Crohn Disease / Q000188:drug therapy*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008875:Middle Aged; D012008:Recurrence
D007166:Immunosuppressive Agents; D001379:Azathioprine