Published online Oct 28, 2016. doi: 10.3748/wjg.v22.i40.9012
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.
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.