Indicators of clinical response to treatment with six-mercaptopurine or azathioprine in patients with inflammatory bowel disease

Authors

  • Jean-Paul Achkar MD,

    Corresponding author
    1. Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio
    • Department of Gastroenterology, The Cleveland Clinic Foundation, Desk A30, 9500 Euclid Avenue, Cleveland, OH 44195
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  • Tyler Stevens MD,

    1. Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio
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  • Kirk Easley MS,

    1. Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia
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  • Aaron Brzezinski MD,

    1. Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio
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  • Douglas Seidner MD,

    1. Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio
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  • Bret Lashner MD

    1. Center for Inflammatory Bowel Disease, Departments of Gastroenterology and Biostatistics, The Cleveland Clinic Foundation, Cleveland, Ohio
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Abstract

Objectives:

There is some uncertainty regarding how to best dose and therapeutically monitor 6-mercaptopurine or azathioprine in patients with inflammatory bowel disease. The purpose of this study was to assess the relation between clinical response, 6-mercaptopurine metabolite levels, relative leukopenia, and drug dose.

Methods:

60 patients with inflammatory bowel disease who were on stable doses of 6-mercaptopurine or azathioprine for ≥ 3 months and who had measurements of 6-mercaptopurine metabolite levels were evaluated. Patients were classified as complete responders (N = 24), partial responders (N = 7), or non-responders (N = 29).

Results:

Drug dose was associated with clinical response when we analyzed adjusted doses based on molecular drug weight (P = 0.002). 6-Thioguanine levels also were associated with clinical response (P = 0.003) and the maximal difference between responders and non-responders was seen at 6-thioguanine levels greater than 260 pmol/8 × 108 RBC. Relative leukopenia, defined as white blood cell count less than either 5.0 or 4.0 K/ u L, was not associated with clinical response (P = 0.13 and 0.77 respectively).

Conclusions:

1. Drug dose and 6-thioguanine levels are related to clinical response in patients with inflammatory bowel disease on 6-mercaptopurine or azathioprine. 2. For 6-thioguanine levels, there is a fair amount of overlap, but maximal differentiation between responders and non-responders is seen at levels > 260 pmol/8 × 108 RBC. 3. Relative leukopenia does not correlate well with clinical response.

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