Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse.
OBJECTIVE
Azathioprine (AZA) withdrawal in Crohn's disease after long-term remission under treatment is controversial. In a Groupe d'Etude Thérapeutique des Affections Inflammatoires du tube Digestif randomized, double-blind, placebo-controlled trial, the hypothesis that AZA withdrawal was not inferior to AZA continuation in patients in prolonged clinical remission could not be shown.


METHODS
A cohort of 66 patients in prolonged remission while being treated with AZA who stopped AZA, during or at the end of the randomized controlled trial, underwent long-term follow-up evaluation. The primary end point was clinical relapse. Prognostic factors of relapse were looked for through a proportional hazards model.


RESULTS
Median durations of AZA therapy and of clinical remission were 68.4 months (interquartile range, 52.8-85.2 mo) and 63.6 months (interquartile range, 48.0-55.7 mo), respectively. The median follow-up time after AZA interruption was 54.5 months; 32 of 66 patients had a relapse. The cumulative probabilities +/- SE of relapse at 1, 3, and 5 years were 14.0% +/- 4.3%, 52.8% +/- 7.1%, and 62.7% +/- 7.2%, respectively. C-reactive protein concentration of 20 mg/L or greater (risk, 58.6; 95% confidence interval, 7.5-457; P = .002), hemoglobin level less than 12 g/dL (risk, 4.8; 95% confidence interval, 1.7-13.7; P = .04), and neutrophil count 4 x 10(9)/L or greater (risk, 3.2; 95% confidence interval, 1.6-6.3; P = .003) were associated independently with an increased risk of relapse. Among the 32 relapsing patients, 23 were retreated by AZA alone, all but 1 up to successful remission.


CONCLUSIONS
Our results confirm that AZA withdrawal is associated with a high risk of relapse, whatever the duration of remission under this treatment. These data suggest that if AZA is well tolerated, it should not be interrupted.
Treton
Xavier
X
Hôpital Beaujon, Pôle des Maladies de l'Appareil Digestif, France. xavier.treton@bjn.aphp.fr
Bouhnik
Yoram
Y
Mary
Jean-Yves
JY
Colombel
Jean-Frédéric
JF
Duclos
Bernard
B
Soule
Jean-Claude
JC
Lerebours
Eric
E
Cosnes
Jacques
J
Lemann
Marc
M
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D015331:Cohort Studies; D003424:Crohn Disease / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D012307:Risk Factors; D028761:Withholding Treatment
D006454:Hemoglobins; D007166:Immunosuppressive Agents; D002097:C-Reactive Protein; D001379:Azathioprine