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Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid

Maurits C F J de Rotte1, Ethan den Boer1, Pascal H P de Jong2

  • 1Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, Netherlands.

Annals of the Rheumatic Diseases
|December 4, 2013
PubMed
Abstract

Insights

Higher erythrocyte-methotrexate-polyglutamate (MTX-PG) levels correlate with reduced disease activity in rheumatoid arthritis (RA) patients over nine months. This finding suggests MTX-PG monitoring can optimize methotrexate therapy for RA.

Area of Science:

  • Pharmacology
  • Rheumatology
  • Clinical Chemistry

Background:

  • Rheumatoid arthritis (RA) management often involves methotrexate (MTX).
  • Erythrocyte-methotrexate-polyglutamate (MTX-PG) levels may influence MTX efficacy.
  • Understanding the relationship between MTX-PG and clinical outcomes is crucial for optimizing RA treatment.

Purpose of the Study:

  • To determine if erythrocyte-MTX-PG concentrations are associated with disease activity and adverse events in RA patients treated with MTX.
  • To explore the potential of MTX-PG as a biomarker for therapeutic drug monitoring in RA.

Main Methods:

  • A longitudinal study involving two cohorts (derivation and validation) of RA patients on MTX.
  • Erythrocyte-MTX-PG concentrations (1-5 glutamate residues) were measured using LC-MS/MS at 3, 6, and 9 months post-MTX initiation.
  • Disease activity (DAS28) and adverse events were assessed, with associations analyzed using linear mixed models.

Main Results:

  • An increase in erythrocyte-MTX-PG concentrations (including MTX-PG2, MTX-PG3, MTX-PG4, and total MTX-PG) was significantly associated with a decrease in DAS28 over 9 months in both cohorts.
  • No significant association was found between MTX-PG levels and the occurrence of adverse events.
  • DAS28 scores and adverse event rates were comparable between the derivation and validation cohorts.

Conclusions:

  • Elevated erythrocyte-MTX-PG concentrations are linked to improved disease control in RA patients treated with methotrexate.
  • Erythrocyte-MTX-PG levels represent a promising biomarker for therapeutic drug monitoring to personalize MTX dosing in RA.
  • This study provides the first longitudinal evidence supporting MTX-PG as a tool for optimizing MTX therapy in rheumatoid arthritis.
Keywords:
DMARDs (synthetic)PharmacokineticsRheumatoid Arthritis

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