Critical assessment of thioguanine treatment for Inflammatory Bowel Diseases: is it time to rehabilitate this treatment?

Abstract

OBJECTIVE: The potential therapeutic effect of thioguanine in the management of inflammatory bowel disease (IBD) is hindered due to association with vascular hepatotoxicity. The study aimed to assess the evidence for efficacy of thioguanine in IBD management and the association with nodular regenerative hyperplasia (NRH) and other thioguaninerelated hepatotoxicities. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used for literature search. Due to the lack of randomized controlled trials (RCTs), the search was extended to observational studies. Quality of the included studies were graded A to C based on evaluation tools used to determine efficacy (subjective and objective grading tools) and nodular regenerative hyperplasia safety (liver biopsy and imaging tools). RESULTS: Two hundred and ninety studies were identified, but following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines only 13 studies were evaluated for efficacy and safety of thioguanine. Outcome measures were consistent across the included studies. Thioguanine appeared efficacious and well-tolerated in patients who were intolerant/ non-responsive to existing immunomodulators. There was a trend toward a positive association between dose of thioguanine and NRH but not with other adverse events such as liver biochemical abnormalities or with portal hypertension. CONCLUSIONS: The evidence to support thioguanine treatment is limited to observational studies. While encouraging, there is a need for prospective RCTs to determine the role of thioguanine in the management of IBD.