Background: Thiopurines, including azathioprine, mercaptopurine, and thioguanine (TG), are widely used as maintenance therapies for inflammatory bowel disease (IBD). However, their clinical utility is challenged by interindividual variability in metabolism, therapeutic response, and toxicity. Therapeutic drug monitoring (TDM) and pharmacogenomics have emerged as critical tools for optimizing thiopurine therapies. This review aimed to compare the international guidelines on TDM and the pharmacogenomics of thiopurines in IBD to identify global differences in TDM practices. Methods: A scoping review was conducted using PubMed, Embase, Web of Science, and official Gastroenterology Society web sites. We identified and analyzed international guidelines for thiopurine TDM and pharmacogenomics, focusing on recommendations for metabolite monitoring, thiopurine methyltransferase, and nudix hydrolase 15 (NUDT15) testing. Results: A total of 23 guidelines from North America, Europe, Africa, Asia, Latin America, and Oceania were included in this study. TDM was recommended in 65% of the guidelines with various approaches; some advocated reactive monitoring (6-TGN and/or 6-MMPR in response to treatment failure or adverse effects), whereas others recommended proactive thiopurine monitoring to prevent toxicity. Thiopurine methyltransferase testing is recommended in 74% of these guidelines, although its relevance has been questioned in Asian populations. NUDT15 testing is mentioned in only 13% of the guidelines, despite its established role in predicting thiopurine-induced myelotoxicity, particularly in Asian and Hispanic populations. Accessibility limitations in low-resource regions have led to a reliance on empirical dose adjustments and complete blood count monitoring. Conclusions: There is substantial variability in the global TDM and pharmacogenomic practices for thiopurines in IBD. Limited recommendations for NUDT15 testing and disparities in resource availability have contributed to inconsistent clinical implementation. Future guidelines should address these gaps by integrating cost-effective pharmacogenomic strategies and incorporating alternative monitoring methods such as DNA-TG for NUDT15 variants. This review highlights the variability in the global recommendations for thiopurine TDM and pharmacogenomics. To optimize thiopurine therapy and reduce toxicity risks, future guidelines should include NUDT15 testing and consider TG, low-dose thiopurine, and allopurinol treatments.
Bayoumy et al. (Fri,) studied this question.