Thiopurine metabolite testing in inflammatory bowel disease

Rimma Goldberg, Gregory Moore, Georgina Cunningham, Julien Schulberg, Philip Marsh, Steven Brown, William Connell, Mark Lust, Michael A Kamm, Sally Bell

Research output: Contribution to journalArticleResearchpeer-review

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Abstract

BACKGROUND: Thiopurines use in inflammatory bowel disease (IBD) is limited by drug toxicity and lack of therapeutic efficacy. We assessed the utility of thiopurine metabolite testing and the relationship between disease activity, dose and metabolite levels in a real world setting. METHODS: Patients identified from pathology databases (2007-2012) at 2 tertiary IBD centers were included if they had thiopurines for at least four weeks. Demographics, dose, test indication, clinical status, action taken, and outcome were obtained by retrospective medical record review. RESULTS: 169 patients were included. TGN levels were sub-therapeutic in 52 , therapeutic in 34 , and supratherapeutic in 14 . Test indication was active disease (79 ), adverse effect (11 ), or adherence assessment (7 ). TGN trended lower in the active disease group compared to those with adverse effects (273 (+/- 23.2) vs 447 (+/- 117.7) pmol/8 x 108 RBC, p = 0.05). Weight based dosing did not improve rates of therapeutic TGN levels (under-dosed 31.5 vs standard dose 35.4 ), however was significantly associated with shunting towards 6-MMP (23.1 vs 6.8 , p = 0.008, OR = 4.1). Testing resulted in a change in patient treatment in 86 of patients with active disease and subtherapeutic levels and in 68 of tested patients overall. CONCLUSIONS: Metabolite testing resulted in a change in management in most patients not responding to thiopurines or experiencing adverse events. Weight based dosing did not increase rates of therapeutic levels however was associated with increased 6MMP shunting. This article is protected by copyright. All rights reserved.
Original languageEnglish
Pages (from-to)553-560
Number of pages8
JournalJournal of Gastroenterology and Hepatology
Volume31
Issue number3
DOIs
Publication statusPublished - Mar 2016

Keywords

  • IBD
  • metabolite testing
  • thiopurines

Cite this

Goldberg, Rimma ; Moore, Gregory ; Cunningham, Georgina ; Schulberg, Julien ; Marsh, Philip ; Brown, Steven ; Connell, William ; Lust, Mark ; Kamm, Michael A ; Bell, Sally. / Thiopurine metabolite testing in inflammatory bowel disease. In: Journal of Gastroenterology and Hepatology. 2016 ; Vol. 31, No. 3. pp. 553-560.
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Goldberg, R, Moore, G, Cunningham, G, Schulberg, J, Marsh, P, Brown, S, Connell, W, Lust, M, Kamm, MA & Bell, S 2016, 'Thiopurine metabolite testing in inflammatory bowel disease', Journal of Gastroenterology and Hepatology, vol. 31, no. 3, pp. 553-560. https://doi.org/10.1111/jgh.13210

Thiopurine metabolite testing in inflammatory bowel disease. / Goldberg, Rimma; Moore, Gregory; Cunningham, Georgina; Schulberg, Julien; Marsh, Philip; Brown, Steven; Connell, William; Lust, Mark; Kamm, Michael A; Bell, Sally.

In: Journal of Gastroenterology and Hepatology, Vol. 31, No. 3, 03.2016, p. 553-560.

Research output: Contribution to journalArticleResearchpeer-review

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T1 - Thiopurine metabolite testing in inflammatory bowel disease

AU - Goldberg, Rimma

AU - Moore, Gregory

AU - Cunningham, Georgina

AU - Schulberg, Julien

AU - Marsh, Philip

AU - Brown, Steven

AU - Connell, William

AU - Lust, Mark

AU - Kamm, Michael A

AU - Bell, Sally

PY - 2016/3

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N2 - BACKGROUND: Thiopurines use in inflammatory bowel disease (IBD) is limited by drug toxicity and lack of therapeutic efficacy. We assessed the utility of thiopurine metabolite testing and the relationship between disease activity, dose and metabolite levels in a real world setting. METHODS: Patients identified from pathology databases (2007-2012) at 2 tertiary IBD centers were included if they had thiopurines for at least four weeks. Demographics, dose, test indication, clinical status, action taken, and outcome were obtained by retrospective medical record review. RESULTS: 169 patients were included. TGN levels were sub-therapeutic in 52 , therapeutic in 34 , and supratherapeutic in 14 . Test indication was active disease (79 ), adverse effect (11 ), or adherence assessment (7 ). TGN trended lower in the active disease group compared to those with adverse effects (273 (+/- 23.2) vs 447 (+/- 117.7) pmol/8 x 108 RBC, p = 0.05). Weight based dosing did not improve rates of therapeutic TGN levels (under-dosed 31.5 vs standard dose 35.4 ), however was significantly associated with shunting towards 6-MMP (23.1 vs 6.8 , p = 0.008, OR = 4.1). Testing resulted in a change in patient treatment in 86 of patients with active disease and subtherapeutic levels and in 68 of tested patients overall. CONCLUSIONS: Metabolite testing resulted in a change in management in most patients not responding to thiopurines or experiencing adverse events. Weight based dosing did not increase rates of therapeutic levels however was associated with increased 6MMP shunting. This article is protected by copyright. All rights reserved.

AB - BACKGROUND: Thiopurines use in inflammatory bowel disease (IBD) is limited by drug toxicity and lack of therapeutic efficacy. We assessed the utility of thiopurine metabolite testing and the relationship between disease activity, dose and metabolite levels in a real world setting. METHODS: Patients identified from pathology databases (2007-2012) at 2 tertiary IBD centers were included if they had thiopurines for at least four weeks. Demographics, dose, test indication, clinical status, action taken, and outcome were obtained by retrospective medical record review. RESULTS: 169 patients were included. TGN levels were sub-therapeutic in 52 , therapeutic in 34 , and supratherapeutic in 14 . Test indication was active disease (79 ), adverse effect (11 ), or adherence assessment (7 ). TGN trended lower in the active disease group compared to those with adverse effects (273 (+/- 23.2) vs 447 (+/- 117.7) pmol/8 x 108 RBC, p = 0.05). Weight based dosing did not improve rates of therapeutic TGN levels (under-dosed 31.5 vs standard dose 35.4 ), however was significantly associated with shunting towards 6-MMP (23.1 vs 6.8 , p = 0.008, OR = 4.1). Testing resulted in a change in patient treatment in 86 of patients with active disease and subtherapeutic levels and in 68 of tested patients overall. CONCLUSIONS: Metabolite testing resulted in a change in management in most patients not responding to thiopurines or experiencing adverse events. Weight based dosing did not increase rates of therapeutic levels however was associated with increased 6MMP shunting. This article is protected by copyright. All rights reserved.

KW - IBD

KW - metabolite testing

KW - thiopurines

UR - http://www.ncbi.nlm.nih.gov/pubmed/26510636

U2 - 10.1111/jgh.13210

DO - 10.1111/jgh.13210

M3 - Article

VL - 31

SP - 553

EP - 560

JO - Journal of Gastroenterology and Hepatology

JF - Journal of Gastroenterology and Hepatology

SN - 0815-9319

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