Azathioprine withdrawal in patients with Crohn's disease maintained on prolonged remission: a high risk of relapse.

Abstract

BACKGROUND & AIMS:

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.

• Authors: Xavier Treton, Yoram Bouhnik, Jean-Yves Mary, Jean-Frédéric Colombel, Bernard Duclos, Jean-Claude Soule, Eric Lerebours, Jacques Cosnes, Marc Lemann, Groupe D'Etude Thérapeutique Des Affections Inflammatoires Du Tube Digestif (GETAID)
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 7 Issue 1 Pg. 80-5 (Jan 2009) ISSN: 1542-7714 [Electronic] United States
• PMID: 18849016 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hemoglobins
• Immunosuppressive Agents
• C-Reactive Protein
• Azathioprine

Topics

• Adult
• Azathioprine (therapeutic use)
• C-Reactive Protein (analysis)
• Cohort Studies
• Crohn Disease (drug therapy)
• Female
• Follow-Up Studies
• Hemoglobins (analysis)
• Humans
• Immunosuppressive Agents (therapeutic use)
• Leukocyte Count
• Male
• Middle Aged
• Recurrence
• Risk Factors
• Withholding Treatment