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

  • de Rotte M
  • den Boer E
  • de Jong P
 et al. 
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Objective: To investigate if erythrocyte-methotrexate-polyglutamate (MTX-PG) concentrations in patients with rheumatoid arthritis (RA) are associated with disease activity or adverse events., Methods: We used a longitudinal study design with two cohorts. The derivation cohort included 102 and the validation cohort included 285 patients with RA on MTX. We measured erythrocyte-MTX-PG with 1-5 glutamate residues at 3 months, 6 months and 9[white square]months after MTX start with a liquid chromatography (LC)-mass spectrometry (MS)/MS assay. Outcomes were disease activity score in 28 joints (DAS28) and adverse events. Longitudinal associations of MTX-PG concentrations after 3 months, 6 months and 9[white square]months with DAS28 were tested with a linear mixed model adjusted for age, gender, baseline DAS28, MTX dose and comedication., Results: In the derivation cohort, mean DAS28 decreased from 4.26 (SE=0.14) at baseline to 2.72 (SE=0.13) after 9[white square]months. Thirty per cent of patients in the derivation cohort experienced more than three adverse events after 3[white square]months, which decreased to 18% after 9[white square]months. In the validation cohort, DAS28 and adverse events were comparable with the derivation cohort. In the derivation cohort, MTX-PG1 ([beta]=-0.005), MTX-PG2 ([beta]=-0.022), MTX-PG3 ([beta]=-0.007) and total MTX-PG ([beta]=-0.004) were associated (p

Author-supplied keywords

  • DMARDs (synthetic)
  • Pharmacokinetics
  • Rheumatoid Arthritis

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  • Maurits de Rotte

  • Ethan den Boer

  • Pascal de Jong

  • Saskia Pluijm

  • Maja Calasan

  • Angelique Weel

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