Methotrexate Polyglutamate Monitoring in Patients With Crohn's Disease

Monika Fischer, Shivi Siva, Gwendolyn K. Cook, David R. Jones, Hala M. Fadda

Research output: Contribution to journalArticle

3 Scopus citations


Methotrexate is an efficacious immunosuppressant for induction and maintenance of remission in Crohn's disease. The goal of this pilot study was to determine whether total or individual methotrexate glutamate levels (MTXGlun) in red blood cells correlate with disease activity and adverse events in Crohn's disease. A cross-sectional study was undertaken with 12 patients on a stable dose of 25 mg weekly methotrexate (oral or subcutaneous). Clinical disease activity was assessed by the Harvey-Bradshaw Index (HBI), and biologic disease activity was measured by inflammatory markers. Concentrations of individual MTXGlun levels were measured in red blood cells (RBCs) using high-performance liquid chromatography–mass spectrometry. No association was observed between RBC individual (MTXGlun) or total methotrexate glutamate concentrations and clinical disease activity (HBI score) or inflammatory markers or adverse events. Although Crohn's disease patients in remission appeared to generally have higher RBC total longer-chain methotrexate polyglutamate (MTXGlu3+4+5) concentrations compared with those with active disease, a definitive association between RBC MTXGlu3+4+5 levels and clinical disease activity could not be established. Larger longitudinal studies in patients with diverse disease activity are needed to establish the value of MTXGlun levels as indicators of treatment efficacy and clinical outcome.

Original languageEnglish (US)
Pages (from-to)240-245
Number of pages6
JournalClinical Pharmacology in Drug Development
Issue number3
StatePublished - May 1 2017


  • bioavailability
  • immunosuppressant
  • inflammatory bowel disease
  • methotrexate polyglutamate
  • therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Pharmacology (medical)

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