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Risk factors for thiopurine-induced myelosuppression and infections in inflammatory bowel disease patients with a

M M T J Broekman1, M J H Coenen2, G J Wanten1

  • 1Department of Gastroenterology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Alimentary Pharmacology & Therapeutics
|September 16, 2017
PubMed
Abstract

Insights

Thiopurine-induced leucopenia risk factors in patients without TPMT variants include lower baseline white blood cell (WBC) counts and mercaptopurine use. These findings aid in managing thiopurine therapy and preventing adverse events.

Area of Science:

  • Pharmacogenomics
  • Clinical Pharmacology
  • Inflammatory Bowel Disease Management

Background:

  • Leucopenia is a frequent adverse event in patients receiving thiopurine medications.
  • Genetic variants in thiopurine S-methyltransferase (TPMT) are known risk factors but do not account for all cases of leucopenia.

Purpose of the Study:

  • To identify clinical risk factors for thiopurine-induced leucopenia in patients lacking common TPMT variants.
  • To investigate the association between these risk factors and the incidence of infections.

Main Methods:

  • A post hoc analysis of the TOPIC trial included patients without TPMT variants (*2, *3A, *3C).
  • Cox-proportional hazard models were employed to determine risk factors for leucopenia and infections.
  • Leucopenia was defined as a white blood cell (WBC) count <3.0 × 10^9 /L.

Main Results:

  • Among 695 patients without TPMT variants, 6.5% developed leucopenia.
  • Mercaptopurine use (vs. azathioprine) significantly increased leucopenia risk (HR 2.61).
  • Higher baseline WBC count was protective (HR 0.80), while older age and biologic drug use increased infection risk.

Conclusions:

  • Low baseline WBC count and mercaptopurine are significant risk factors for thiopurine-induced leucopenia in patients without TPMT variants.
  • These findings highlight the need for careful monitoring and personalized dosing strategies in this patient population.

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