Proactive Metabolite Testing in Patients on Thiopurine May Yield Long-Term Clinical Benefits in Inflammatory Bowel Disease

Alex Barnes, Soong Yuan J. Ooi, Kate D. Lynch, Nina Parthasarathy, Maria Bishara, Michael Gounder, Rachel Grafton, Peta Leach, Peter Bampton, Alexandra Sechi, Watson Ng, Susan Connor, Daniel van Langenberg, Réme Mountifield, Jane M. Andrews

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)
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Background: The thiopurine medications are well established in the treatment of inflammatory bowel disease (IBD). There is significant variation in levels of toxic and therapeutic metabolites. Current data from small or short-term studies support therapeutic drug monitoring (TDM) in assessing azathioprine (AZA) and 6-mercaptopurine (6MP). TDM of thiopurines involves measurement and interpretation of metabolites 6-TGN and 6-MMPR. 

Aims: This study aimed to assess long-cterm outcomes of patients on thiopurines following therapeutic drug monitoring.

Methods: A multicenter retrospective observational study of outcomes post thiopurine TDM was conducted. Demographics, disease characteristics, physician global assessment, IBD therapy at baseline TDM and again at 12 months were collected. Clinical outcomes were analyzed according to TDM result, and indication for TDM including proactive and other indications. 

Results: The study included 541 patients. Only 39% of patients had appropriate dosing of thiopurines. AZA/6MP TDM informed a management change in 61.9%, and enabled 88.8% of the cohort to continue AZA/6MP following TDM. At 12 months following TDM the majority (74.1%) of the cohort remained on AZA/6MP. Clinical remission was higher at 12-months following thiopurines TDM (68%) compared to baseline (37%), including proactive TDM. Post TDM, 13.0% of patients were identified as shunters and commenced on thiopurine-allopurinol co-therapy. 

Conclusion: Thiopurine TDM resulted in a change in management for the majority of patients. Post TDM significantly more patients were in remission. TDM allowed the identification of non-adherence and shunters who, without intervention, would not reach therapeutic drug levels. Proactive TDM allowed identification and management of inappropriate dosing, and was associated with increased levels of clinical remission.

Original languageEnglish
Pages (from-to)889-896
Number of pages8
JournalDigestive Diseases and Sciences
Issue number3
Early online date10 Jun 2022
Publication statusPublished - Mar 2023


  • Adverse drug reactions
  • Clinical pharmacology
  • Inflammatory bowel disease
  • Therapeutic drug monitoring
  • Thiopurine metabolite measurement
  • Thiopurines


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