Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy.

L.P. Gilissen, D.R. Wong, L.G.B. Engels, J. Bierau, J.A. Bakker, A.D.C. Paulussen, M. Romberg-Camps, A. Stronkhorst, P. Bus, L.P. Bos, P.M. Hooymans, R.W. Stockbrügger, C.K. Neef, A.A.M. Masclee

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Abstract

BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is >/=235pmol/8x10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263pmol/8x10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235pmol/8x10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response.
Original languageEnglish
Pages (from-to)698-707
JournalJournal of Crohn's & Colitis
Volume6
Issue number6
DOIs
Publication statusPublished - 1 Jan 2012

Cite this

Gilissen, L.P. ; Wong, D.R. ; Engels, L.G.B. ; Bierau, J. ; Bakker, J.A. ; Paulussen, A.D.C. ; Romberg-Camps, M. ; Stronkhorst, A. ; Bus, P. ; Bos, L.P. ; Hooymans, P.M. ; Stockbrügger, R.W. ; Neef, C.K. ; Masclee, A.A.M. / Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy. In: Journal of Crohn's & Colitis. 2012 ; Vol. 6, No. 6. pp. 698-707.
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title = "Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy.",
abstract = "BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is >/=235pmol/8x10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one patients had an exacerbation, 59 patients were in remission. In 17{\%} of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263pmol/8x10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235pmol/8x10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63{\%}) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41{\%}) in clinical remission (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response.",
author = "L.P. Gilissen and D.R. Wong and L.G.B. Engels and J. Bierau and J.A. Bakker and A.D.C. Paulussen and M. Romberg-Camps and A. Stronkhorst and P. Bus and L.P. Bos and P.M. Hooymans and R.W. Stockbr{\"u}gger and C.K. Neef and A.A.M. Masclee",
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Gilissen, LP, Wong, DR, Engels, LGB, Bierau, J, Bakker, JA, Paulussen, ADC, Romberg-Camps, M, Stronkhorst, A, Bus, P, Bos, LP, Hooymans, PM, Stockbrügger, RW, Neef, CK & Masclee, AAM 2012, 'Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy.', Journal of Crohn's & Colitis, vol. 6, no. 6, pp. 698-707. https://doi.org/10.1016/j.crohns.2011.12.003

Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy. / Gilissen, L.P.; Wong, D.R.; Engels, L.G.B.; Bierau, J.; Bakker, J.A.; Paulussen, A.D.C.; Romberg-Camps, M.; Stronkhorst, A.; Bus, P.; Bos, L.P.; Hooymans, P.M.; Stockbrügger, R.W.; Neef, C.K.; Masclee, A.A.M.

In: Journal of Crohn's & Colitis, Vol. 6, No. 6, 01.01.2012, p. 698-707.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Therapeutic drug monitoring of thiopurine metabolites in adult thiopurine tolerant IBD patients on maintenance therapy.

AU - Gilissen, L.P.

AU - Wong, D.R.

AU - Engels, L.G.B.

AU - Bierau, J.

AU - Bakker, J.A.

AU - Paulussen, A.D.C.

AU - Romberg-Camps, M.

AU - Stronkhorst, A.

AU - Bus, P.

AU - Bos, L.P.

AU - Hooymans, P.M.

AU - Stockbrügger, R.W.

AU - Neef, C.K.

AU - Masclee, A.A.M.

PY - 2012/1/1

Y1 - 2012/1/1

N2 - BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is >/=235pmol/8x10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263pmol/8x10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235pmol/8x10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response.

AB - BACKGROUND AND AIMS: Therapeutic drug monitoring of active metabolites of thiopurines, azathioprine and 6-mercaptopurine, is relatively new. The proposed therapeutic threshold level of the active 6-thioguanine nucleotides (6-TGN) is >/=235pmol/8x10(8) erythrocytes. The aim of this prospective cross-sectional study was to compare 6-TGN levels in adult thiopurine tolerant IBD patients with an exacerbation with those in remission, and to determine the therapeutic 6-TGN cut-off level. METHODS: Hundred IBD patients were included. Outcome measures were thiopurine metabolite levels, calculated therapeutic 6-TGN cut-off level, CDAI/CAI scores, thiopurine dose and TPMT enzyme activity. RESULTS: Forty-one patients had an exacerbation, 59 patients were in remission. In 17% of all patients 6-TGN levels were compatible with non-compliance. The median 6-TGN levels were not significantly different between the exacerbation and remission group (227 versus 263pmol/8x10(8) erythrocytes, p=0.29). The previous reported therapeutic 6-TGN cut-off level of 235pmol/8x10(8) erythrocytes was confirmed in this study. Twenty-six of the 41 patients (63%) with active disease had 6-TGN levels below this threshold and 24 of 59 IBD patients (41%) in clinical remission (p=0.04). CONCLUSIONS: Thiopurine non-compliance occurs frequently both in active and quiescent disease. 6-TGN levels below or above the therapeutic threshold are associated with a significant higher chance of IBD exacerbation and remission, respectively. These data support the role of therapeutic drug monitoring in thiopurine maintenance therapy in IBD to reveal non-compliance or underdosing, and can be used as a practical tool to optimize thiopurine therapy, especially in case of thiopurine non-response.

U2 - 10.1016/j.crohns.2011.12.003

DO - 10.1016/j.crohns.2011.12.003

M3 - Article

VL - 6

SP - 698

EP - 707

JO - Journal of Crohn's & Colitis

JF - Journal of Crohn's & Colitis

SN - 1873-9946

IS - 6

ER -