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Therapeutic drug monitoring of thiopurines: Effect of reduced 6-thioguanine nucleotide target levels in IBD patients
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  • Monique Boekema,
  • Carmen Horjus,
  • Britt Roosenboom,
  • Lian Roovers,
  • Matthijs van Luin
Monique Boekema
Rijnstate Hospital

Corresponding Author:mboekema@rijnstate.nl

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Carmen Horjus
Rijnstate Hospital
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Britt Roosenboom
Rijnstate Hospital
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Lian Roovers
Rijnstate Hospital
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Matthijs van Luin
University Medical Centre
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Abstract

Aim: The effect of the Dutch nationwide adjustment of reduced 6-TGN target values (from 600-1200 pmol/8x108 RBC to 320-630 pmol/8x108 RBC) on toxicity and clinical outcome of thiopurine treatment in patients with inflammatory bowel disease (IBD) has not yet been established. Therefore the authors determined the incidence of toxicity-induced discontinuations and efficacy at both target concentrations. Methods: This retrospective study was performed in IBD patients treated with azathioprine or mercaptopurine. Two groups were defined: the former target (FT) group with target concentrations of 600-1200 pmol/8x10^8 RBC and the adjusted target (AT) group with target concentrations of 320-630 pmol/8x10^8 RBC. Patients were followed for maximum 52 weeks or until discontinuation of thiopurine therapy. Data were collected from the local hospital electronic health software of Rijnstate Hospital. Results: 151 patients were included, 76 in the FT group and 75 in the AT group. At week 52, 100 out of 150 patients (66%) of the total population discontinued thiopurine therapy. Forty-eight of this discontinuations were due toxicity (48%). The estimated cumulative incidence of toxicity was higher in the FT group compared to the AT group (47% and 35% respectively, p=0.25). No loss of efficacy was seen in the AT group. Conclusion: Reduction of the target range may lead to less toxicity induced discontinuations. In addition, this study did not find any indication that the reduction of the target range diminished efficacy.
03 Dec 2021Submitted to British Journal of Clinical Pharmacology
06 Dec 2021Submission Checks Completed
06 Dec 2021Assigned to Editor
08 Dec 2021Reviewer(s) Assigned
24 Dec 2021Review(s) Completed, Editorial Evaluation Pending
28 Dec 2021Editorial Decision: Revise Major
21 Feb 20221st Revision Received
22 Feb 2022Assigned to Editor
22 Feb 2022Submission Checks Completed
22 Feb 2022Review(s) Completed, Editorial Evaluation Pending
23 Feb 2022Reviewer(s) Assigned
03 Mar 2022Editorial Decision: Revise Minor
04 Mar 20222nd Revision Received
07 Mar 2022Assigned to Editor
07 Mar 2022Submission Checks Completed
07 Mar 2022Review(s) Completed, Editorial Evaluation Pending
08 Mar 2022Editorial Decision: Accept
16 Mar 2022Published in British Journal of Clinical Pharmacology. 10.1111/bcp.15315