» Articles » PMID: 21476031

Relapse Rate Following Azathioprine Withdrawal in Maintaining Remission for Crohn's Disease: a Meta-analysis

Overview
Journal Dig Dis Sci
Specialty Gastroenterology
Date 2011 Apr 9
PMID 21476031
Citations 17
Authors
Affiliations
Soon will be listed here.
Abstract

Background: The duration of use of azathioprine (Aza) and 6-mercaptopurine (6-MP) for maintaining remission for Crohn's disease is debatable.

Aim: To examine whether Aza/6-MP can be safely withdrawn in patients with Crohn's disease who have been in remission.

Methods: The following databases were searched: MEDLINE (1950-September 2010), EMBASE (1980-September 2010), CINHAL (1981-September 2010), PubMed (1950-September 2010), and the Cochrane Central Register of Controlled Trials (CENTRAL). Randomised controlled and cohort studies comparing azathioprine continuation versus placebo or no treatment were eligible for inclusion. Primary outcomes were relapse rate after discontinuation of Aza/6-MP at 6, 12, and 18 months, and 5 and 10 years.

Results: Five studies, with 256 patients and 168 controls, met the inclusion criteria. Stopping azathioprine/6-MP was found to significantly increase the risk of relapse at 6, 12, and 18 months with pooled odds ratios of 0.22 (95% CI 0.09-0.53), 0.25 (95% CI 0.11-0.56), and 0.35 (95% CI 0.21-0.6), respectively. Two trials examined relapse rate at 5 years with pooled OR 0.53 (95% CI 0.13-2.21). No trials looking at relapse rates beyond 5 years were identified.

Conclusions: There is a clear benefit of continuing Aza/6-MP for at least 18 months to maintain remission for Crohn's disease patients who established remission. There is not enough evidence to provide clear guidance on whether or not to continue Aza/6-MP treatment beyond 18 months. Well-designed randomised controlled trials addressing this issue are needed.

Citing Articles

Common Mistakes in Managing Patients with Inflammatory Bowel Disease.

Gisbert J, Chaparro M J Clin Med. 2024; 13(16).

PMID: 39200937 PMC: 11355176. DOI: 10.3390/jcm13164795.


Azathioprine promotes intestinal epithelial cell differentiation into Paneth cells and alleviates ileal Crohn's disease severity.

Ragab M, Schlichting H, Hicken M, Mester P, Hirose M, Almeida L Sci Rep. 2024; 14(1):12879.

PMID: 38839896 PMC: 11153537. DOI: 10.1038/s41598-024-63730-4.


Discontinuation of therapy in inflammatory bowel disease: Current views.

Mestrovic A, Kumric M, Bozic J World J Clin Cases. 2024; 12(10):1718-1727.

PMID: 38660068 PMC: 11036474. DOI: 10.12998/wjcc.v12.i10.1718.


Thiopurine Methyltransferase Activity and Thiopurine Metabolites in Inflammatory Bowel Disease.

El-Matary W Crohns Colitis 360. 2023; 2(3):otaa062.

PMID: 36798512 PMC: 9927816. DOI: 10.1093/crocol/otaa062.


Clinical Considerations Regarding the Use of Thiopurines in Older Patients with Inflammatory Bowel Disease.

Calafat M, Manosa M, Canete F, Domenech E Drugs Aging. 2021; 38(3):193-203.

PMID: 33438138 DOI: 10.1007/s40266-020-00832-4.


References
1.
Bouhnik Y, Lemann M, Mary J, Scemama G, Tai R, Matuchansky C . Long-term follow-up of patients with Crohn's disease treated with azathioprine or 6-mercaptopurine. Lancet. 1996; 347(8996):215-9. DOI: 10.1016/s0140-6736(96)90402-x. View

2.
Bernstein C, Fried M, Krabshuis J, Cohen H, Eliakim R, Fedail S . World Gastroenterology Organization Practice Guidelines for the diagnosis and management of IBD in 2010. Inflamm Bowel Dis. 2009; 16(1):112-24. DOI: 10.1002/ibd.21048. View

3.
Holtmann M, Krummenauer F, Claas C, Kremeyer K, Lorenz D, Rainer O . Long-term effectiveness of azathioprine in IBD beyond 4 years: a European multicenter study in 1176 patients. Dig Dis Sci. 2006; 51(9):1516-24. DOI: 10.1007/s10620-005-9037-5. View

4.
Jadad A, Moore R, Carroll D, Jenkinson C, Reynolds D, Gavaghan D . Assessing the quality of reports of randomized clinical trials: is blinding necessary?. Control Clin Trials. 1996; 17(1):1-12. DOI: 10.1016/0197-2456(95)00134-4. View

5.
ODonoghue D, Dawson A, Powell-Tuck J, Bown R, Lennard-Jones J . Double-blind withdrawal trial of azathioprine as maintenance treatment for Crohn's disease. Lancet. 1978; 2(8097):955-7. DOI: 10.1016/s0140-6736(78)92524-2. View