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Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in juvenile idiopathic arthritis patients
  1. Maja Bulatović Ćalasan1,
  2. Ethan den Boer2,
  3. Maurits C F J de Rotte2,
  4. Sebastiaan J Vastert1,
  5. Sylvia Kamphuis3,
  6. Robert de Jonge2,
  7. Nico M Wulffraat1
  1. 1Department of Paediatric Immunology, University Medical Centre Utrecht, Wilhelmina Children's Hospital, Utrecht, The Netherlands
  2. 2Department of Clinical Chemistry, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
  3. 3Department of Paediatric Rheumatology, Erasmus University Medical Centre Rotterdam, Sophia Children's Hospital, Rotterdam, The Netherlands
  1. Correspondence to Maja Bulatović Ćalasan, Department of Pediatric Immunology, University Medical Centre Utrecht, Wilhelmina Children's Hospital, Room KC 03.063.0, PO Box 85090, Utrecht 3508 AB, The Netherlands; m.bulatovic{at}umcutrecht.nl

Abstract

Objective To determine association of erythrocyte methotrexate polyglutamates (MTX-PG) with disease activity and adverse effects in a prospective juvenile idiopathic arthritis (JIA) cohort.

Methods One hundred and thirteen JIA patients were followed from MTX start until 12 months. Erythrocyte MTX-PGs with 1–5 glutamate residues were measured at 3 months with tandem mass spectrometry. The outcomes were Juvenile Arthritis Disease Activity Score (JADAS)-27 and adverse effects. To determine associations of MTX-PGs with JADAS-27 at 3 months and during 1 year of MTX treatment, linear regression and linear mixed-model analyses were used. To determine associations of MTX-PGs with adverse effects during 1 year of MTX treatment, logistic regression was used. Analyses were corrected for JADAS-27 at baseline and co-medication.

Results Median JADAS-27 decreased from 12.7 (IQR: 7.8–18.2) at baseline to 2.9 (IQR: 0.1–6.5) at 12 months. Higher concentrations of MTX-PG3 (β: −0.006, p=0.005), MTX-PG4 (β: −0.015, p=0.004), MTX-PG5 (β: −0.051, p=0.011) and MTX-PG3–5 (β: −0.004, p=0.003) were associated with lower disease activity at 3 months. Higher concentrations of MTX-PG3 (β: −0.005, p=0.028), MTX-PG4 (β: −0.014, p=0.014), MTX-PG5 (β: −0.049, p=0.023) and MTX-PG3–5 (β: −0.004, p=0.018) were associated with lower disease activity over 1 year. None of the MTX-PGs was associated with adverse effects.

Conclusions In the first prospective study in JIA, long-chain MTX-PGs were associated with lower JADAS-27 at 3 months and during 1 year of MTX treatment. Erythrocyte MTX-PG could be a plausible candidate for therapeutic drug monitoring of MTX in JIA.

  • Disease Activity
  • Methotrexate
  • Juvenile Idiopathic Arthritis
  • Treatment
  • DMARDs (synthetic)

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