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Journal of Crohn's and Colitis: 9 (5)


Laurence J. Egan, Ireland

Associate Editors

Maria T. Abreu, USAShomron Ben-Horin, IsraelSilvio Danese, ItalyPeter Lakatos, HungaryMiles Parkes, UKGijs van den Brink, NLSéverine Vermeire, Belgium


Published on behalf of

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

Lennard P.L. Gilissen , Dennis R. Wong , Leopold G.J.B. Engels , Jörgen Bierau , Jaap A. Bakker , Aimée D.C. Paulussen , Mariëlle J. Romberg-Camps , Arnold Stronkhorst , Paul Bus , Laurens P. Bos , Piet M. Hooymans , Reinhold W. Stockbrügger , Cees Neef , Ad A.M. Masclee
DOI: http://dx.doi.org/10.1016/j.crohns.2011.12.003 698-707 First published online: 1 July 2012


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 ≥ 235 pmol/8 × 108 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 263 pmol/8 × 108 erythrocytes, p = 0.29). The previous reported therapeutic 6-TGN cut-off level of 235 pmol/8 × 108 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

  • Inflammatory bowel disease
  • Thiopurines
  • Azathioprine
  • 6-Mercaptopurine
  • Therapeutic drug monitoring
  • Non-compliance
  • Abbreviations:
    Colitis Activity Index
    Crohn's Disease Activity Index
    CI 95%
    95% confidence interval
    high performance liquid chromatography
    inflammatory bowel disease
    6-methylmercaptopurine ribonucleotides
    patient number
    odds ratio
    red blood cells
    therapeutic drug monitoring
    6-thioguanine nucleotides
    thiopurine S-methyltransferase
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