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

• Published in: Digestive diseases and sciences 2023-03, Vol.68 (3), p.889-896
• Main Authors: Barnes, Alex, Ooi, Soong-Yuan J., Lynch, Kate D., Parthasarathy, Nina, Bishara, Maria, Gounder, Michael, Grafton, Rachel, Leach, Peta, Bampton, Peter, Sechi, Alexandra, Ng, Watson, Connor, Susan, van Langenberg, Daniel, Mountifield, Réme, Andrews, Jane M.
• Format: Article
• Language: English
• Subjects: Azathioprine; Azathioprine - adverse effects; Biochemistry; Care and treatment; Drug dosages; Gastroenterology; Gastrointestinal diseases; Health aspects; Hepatology; Humans; Immunosuppressive Agents - adverse effects; Inflammatory bowel disease; Inflammatory Bowel Diseases - chemically induced; Inflammatory Bowel Diseases - diagnosis; Inflammatory Bowel Diseases - drug therapy; Medical colleges; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Mercaptopurine; Mercaptopurine - adverse effects; Metabolites; Methylthioinosine - therapeutic use; Oncology; Original; Original Article; Political aspects; Remission (Medicine); Retrospective Studies; Therapeutic drug monitoring; Transplant Surgery
• ISSN: 0163-2116; 1573-2568
• DOI: 10.1007/s10620-022-07556-y

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.