Early prediction of thiopurine‐induced hepatotoxicity in inflammatory bowel disease

Abstract

In more than 80% of patients, thiopurine-induced hepatotoxicity could be explained by elevated T1 6-MMPR concentrations and the independent risk factors age, gender and BMI, allowing personalised thiopurine treatment in IBD to prevent early failure.

Editorial: can we get more clinical benefit from thiopurine metabolite testing? Authors’ reply

“…Thiopurine‐induced hepatotoxicity is related to elevated 6‐MMPR metabolite concentrations and often results in treatment discontinuation or dose adaptation . We agree with Professor Fraser that the discriminative value of 6‐MMPR metabolites to predict hepatotoxicity is rather poor for use in clinical practice (AUC 0.65).…”

“…We thank Professor Fraser for the Editorial on the clinical benefits from thiopurine metabolite testing with respect to our recent report on predicting thiopurine‐induced hepatotoxicity …”

Editorial: can we get more clinical benefit from thiopurine metabolite testing?

“…The paper by Wong et al . proposes a clinical role for testing 6‐methylmercaptopurine ribonucleotide (MMPR) levels 1 week after initiating thiopurine treatment . The value of 6‐thioguanine (TGN) testing is now established for optimising thiopurine dosing and, to a lesser extent, for the prevention of myelotoxicity .…”

“…However, many patients will have abnormal liver tests with levels of 6‐MMPR below this threshold (the sensitivity of the chosen threshold was only 42%). Identifying risk factors such as age, male gender, high BMI and hepatic steatosis can also alert the prescriber to the risk of abnormal liver tests …”

“…The principle of early metabolite testing is given some support from these two papers by Wong et al . and some useful thresholds are suggested for making clinical decisions . There should be dose reduction if there is a high 6‐TGN and 6‐MMPR to prevent myelotoxicity.…”