Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2016; 22(40): 9012-9021
Published online Oct 28, 2016. doi: 10.3748/wjg.v22.i40.9012
Efficacy of thioguanine treatment in inflammatory bowel disease: A systematic review
Berrie Meijer, Chris JJ Mulder, Godefridus J Peters, Adriaan A van Bodegraven, Nanne KH de Boer
Berrie Meijer, Chris JJ Mulder, Adriaan A van Bodegraven and Nanne KH de Boer, Department of Gastroenterology and Hepatology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Godefridus J Peters, Department of Medical Oncology, VU University Medical Center, 1081 HV Amsterdam, The Netherlands
Adriaan A van Bodegraven, Department of Gastroenterology, Geriatrics, Internal and Intensive Care Medicine (Co-MIK), Zuyderland Medical Center, Dr. H. van der Hoffplein 1, 6162 BG Sittard-Geleen, The Netherlands
Author contributions: Meijer B finished the manuscript; Meijer B and Peters GJ developed the figure; Meijer B, van Bodegraven AA and de Boer NKH conceived the study; Meijer B, van Bodegraven AA and de Boer NKH analyzed and interpreted the data; Meijer B and de Boer NKH collected all data; Meijer B and de Boer NKH drafted the manuscript; Mulder CJJ and Peters GJ revised the manuscript critically; de Boer NKH was the guarantor of the article; all authors commented on drafts of the paper; and approved the final draft of the article.
Conflict-of-interest statement: The Department of Gastroenterology and Hepatology of the VU University Medical Center received an unrestricted research grant by TEVA Pharma BV outside of this submitted work.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Berrie Meijer, MD, Department of Gastroenterology and Hepatology, VU University Medical Center, De Boelelaan 1118, 1081 HV Amsterdam, The Netherlands.
Telephone: +31-20-4440613 Fax: +31-20-4440554
Received: June 2, 2016
Peer-review started: June 3, 2016
First decision: July 12, 2016
Revised: July 20, 2016
Accepted: August 10, 2016
Article in press: August 10, 2016
Published online: October 28, 2016

To critically assess the available literature regarding the efficacy of thioguanine treatment in inflammatory bowel disease (IBD) patients, irrespective of the (hepato-) toxicity profile.


A systematic literature search of the MEDLINE database using PubMed was performed using the keywords “thioguanine”, “6-TG”, “thioguanine”, “inflammatory bowel disease”, “IBD”, “Crohn’s disease”, “Ulcerative colitis” and “effectiveness” in order to identify relevant articles published in English starting from 2000. Reference lists of the included articles were cross-checked for missing articles. Reviewed manuscripts concerning the effectiveness of thioguanine treatment in IBD were reviewed by the authors and the data were extracted. Data were subsequently analyzed with descriptive statistics. Due to the lack of standardized outcomes, a formal meta-analysis was not performed.


A total of 11 applicable studies were found that involved the effectiveness of thioguanine therapy in IBD. Eight studies were conducted in a prospective manner, in the remaining three studies, data was collected retrospectively. In total, 353 IBD-patients (225 patients with Crohn’s disease, 119 with ulcerative colitis and nine with unclassified IBD) with prior azathioprine/mercaptopurine resistance and/or intolerance (n = 321) or de novo thioguanine administration (n = 32) were included for analysis, of which 228 (65%) had clinical improvement on thioguanine therapy, based on standard IBD questionnaires, biochemical parameters or global physician assessments. Short-term results were based on 268 treatment years (median follow-up 9 mo, range 3-22 mo) with a median daily dose of 20 mg (range 10-80 mg). Discontinuation, mostly due to adverse events, was reported in 72 patients (20%).


The efficacy of thioguanine therapy in IBD patients intolerant to conventional thiopurine therapy is observed in 65%, with short term adverse events in 20% of patients.

Keywords: Thiopurines, Thioguanine, Inflammatory bowel disease, Crohn’s disease, Ulcerative colitis

Core tip: Whereas conventional thiopurines are globally accepted as second-line treatment of inflammatory bowel disease (IBD) patients, almost half of these patients discontinues this treatment due to ineffectiveness or intolerance. In this systematic review, the efficacy of thioguanine treatment, a thiopurine with a less extensive and complex metabolism, is systematically assessed to determine if this drug is an alternative in the treatment of IBD patients intolerant or ineffective to azathioprine and/or mercaptopurine. We showed that up to 65% of patients benefit of a switch to thioguanine, thus preserving these patients from potentially more harmful and expensive treatment with biologicals.