Withdrawal of long-term maintenance treatment with azathioprine tends to increase relapse risk in patients with Crohn's disease.
OBJECTIVE
Many patients with quiescent Crohn's disease are maintained on long-term treatment with azathioprine (AZA), but controlled data are limited. We aimed to evaluate the efficacy of AZA therapy for more than 4 years to maintain clinical remission.


METHODS
We performed a randomized double-blind placebo-controlled AZA withdrawal trial with a follow-up period of 24 months. Patients had to have continuous AZA therapy ≥ 4 years without exacerbation of disease during the 12 months before enrollment, and a Crohn's disease activity index < 150 at baseline. Patients were randomized to continue on AZA or switch to placebo. The primary endpoint was time to clinical relapse during follow-up.


RESULTS
After inclusion of 52 patients, the trial was stopped prematurely due to slow recruitment. During the 2-year follow-up, clinical relapse occurred in 4 of 26 (15 %) patients on continued AZA and in 8 of 26 (31 %) patients on placebo. Time to clinical relapse averaged 22.3 months (95 % CI 20.6-24.0) on AZA and 19.2 months (95 % CI 16.4-22.1) on placebo (p = 0.20). According to life-table analysis, the proportion of patients in remission after 12 and 24 months was 96 ± 4 and 86 ± 7 % in patients receiving AZA versus 76 ± 8 and 68 ± 9 % in patients receiving placebo (month 12, p = 0.035; month 24, p = 0.30). A higher AZA dose at enrollment was an independent predictor for relapse (p < 0.05).


CONCLUSIONS
AZA withdrawal resulted in a significantly increased relapse risk after 1 year and a nonstatistically significant trend for relapse after 2 years. Our results are in line with previous observations.
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria, heimo.wenzl@klinikum-graz.at.
Heimo H
HH
Wenzl
Christian
C
Primas
Gottfried
G
Novacek
Alexander
A
Teml
Anna
A
Öfferlbauer-Ernst
Christoph
C
Högenauer
Harald
H
Vogelsang
Wolfgang
W
Petritsch
Walter
W
Reinisch
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001317:Austria; D001379:Azathioprine / Q000008:administration & dosage*; D003424:Crohn Disease / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D057239:Early Termination of Clinical Trials; D005260:Female; D005765:Gastrointestinal Agents / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D005765:Gastrointestinal Agents; D001379:Azathioprine