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Purpose  Thiopurine drugs are well established treatments in the management of inflammatory bowel disease (IBD), but their use is limited by significant adverse drug reactions (ADRs). Thiopurine S-methyltransferase ( TPMT ) is an important enzyme involved in thiopurine metabolism. Several clinical guidelines recommend determining  TPMT  genotype or phenotype before initiating thiopurine therapy. Although several studies have investigated the association between  TPMT  polymorphisms and thiopurine-induced ADRs, the results are inconsistent. The purpose of this study is to evaluate whether there is an association between  TPMT  polymorphisms and thiopurine-induced ADRs using meta-analysis.    Methods  We explored PubMed, Web of Science and Embase for articles on  TPMT  polymorphisms and thiopurine-induced ADRs. Studies that compared  TPMT  polymorphisms with-ADRs and without-ADRs in IBD patients were included. Relevant outcome data from all the included articles were extracted and the pooled odds ratio (OR) with corresponding 95% confidence intervals were calculated using Revman 5.3 software.    Results  Fourteen published studies, with a total of 2,206 IBD patients, which investigated associations between  TPMT  polymorphisms and thiopurine-induced ADRs were included this meta-analysis. Our meta-analysis demonstrated that  TPMT  polymorphisms were significantly associated with thiopurine-induced overall ADRs and bone marrow toxicity; pooled ORs were 3.36 (95%CI: 1.82–6.19) and 6.67 (95%CI: 3.88–11.47), respectively.  TPMT  polymorphisms were not associated with the development of other ADRs including hepatotoxicity, pancreatitis, gastric intolerance, flu-like symptoms and skin reactions; the corresponding pooled ORs were 1.27 (95%CI: 0.60–2.71), 0.97 (95%CI: 0.38–2.48), 1.82 (95%CI: 0.93–3.53), 1.28 (95%CI: 0.47–3.46) and 2.32 (95%CI: 0.86–6.25), respectively.    Conclusions  Our meta-analysis demonstrated an association of  TPMT  polymorphisms with overall thiopurine-induced ADRs and bone marrow toxicity, but not with hepatotoxicity, pancreatitis, flu-like symptoms, gastric intolerance and skin reactions. These findings suggest that pretesting the  TPMT  genotype could be helpful in clinical practice before initiating thiopurine therapy. However, white blood cell count analysis should be the mainstay for follow-up.

plos one

Association between Thiopurine S-methyltransferase Polymorphisms and Thiopurine-Induced Adverse Drug Reactions in Patients with Inflammatory Bowel Disease: A Meta-Analysis