A randomized, double-blind, controlled withdrawal trial in Crohn's disease patients in long-term remission on azathioprine.
OBJECTIVE
An open study reported that patients with Crohn's disease in remission who have taken azathioprine for longer than 3.5 years are at low risk of relapse when azathioprine is discontinued. To confirm this observation, we performed a multicenter, double-blind, noninferiority withdrawal study.


METHODS
Patients who were in clinical remission on azathioprine for > or = 42 months were randomized to continue azathioprine or to receive an equivalent placebo for 18 months. The primary end point was clinical relapse at 18 months.


RESULTS
Forty patients were randomly assigned to receive azathioprine and 43 to receive placebo. Characteristics of patients at entry were similar in the 2 study groups. At 18 months, 3 patients had a relapse in the azathioprine group, and 9 had a relapse in the placebo group. Kaplan-Meier estimates of the relapse rate at 18 months were 8% +/- 4% and 21% +/- 6%, respectively. The hypothesis that placebo was inferior to azathioprine was not rejected (P = .195). Among the baseline variables, C-reactive protein level > 20 mg/L, time without steroids < 50 months, and hemoglobin level < 12 g/dL were found to be predictive of relapse in the multivariate analysis.


CONCLUSIONS
This study shows that azathioprine withdrawal is not equivalent to continued therapy with azathioprine for maintenance of remission in patients with Crohn's disease who have been in remission on azathioprine for > or = 3.5 years. Thus, azathioprine maintenance therapy should be continued beyond 3.5 years.
Lémann
Marc
M
Hôpital Saint-Louis, Centre Hospitalier Universitaire Lariboisière-Saint-Louis, Paris, France. marc@lemann.com
Mary
Jean-Yves
JY
Colombel
Jean-Frédéric
JF
Duclos
Bernard
B
Soule
Jean-Claude
JC
Lerebours
Eric
E
Modigliani
Robert
R
Bouhnik
Yoram
Y
D000328:Adult; D001379:Azathioprine / Q000008:administration & dosage* / Q000009:adverse effects; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003424:Crohn Disease / Q000188:drug therapy* / Q000473:pathology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D001379:Azathioprine