ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 792

Methotrexate Polyglutamates in Erythrocytes Are Associated With Lower Disease Activity in Juvenile Idiopathic Arthritis Patients

Maja Bulatovic Calasan1, Ethan den Boer2, Maurits C.F.J. De Rotte3, S.J. Vastert4, Sylvia Kamphuis5, Robert De Jonge3 and Nico M. Wulffraat6, 1Paediatric Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands, 2Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, Netherlands, 3Clinical Chemistry, Erasmus Medical Center, Rotterdam, Netherlands, 4Pediatric Rheumatology, University Medical Center Utrecht, Utrecht, Netherlands, 5Pediatric Rheumatology, Eramus MC Sophia Children's Hospital, Rotterdam, Netherlands, 6Pediatric Immunology, University Medical Center Utrecht, Utrecht, Netherlands

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Pediatric Rheumatology: Clinical and Therapeutic Disease: Juvenile Idiopathic Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose:  Methotrexate polyglutamates (MTX-PG) could be biomarkers of MTX response and adverse effects and could thus be used as a therapeutic drug monitoring (TDM) tool to steer tailor-made therapeutic decisions. The aim of this study was to determine association of erythrocyte MTX-PG with disease activity and adverse effects in a prospective juvenile idiopathic arthritis (JIA) cohort.

Methods: One hundred thirteen JIA patients were followed from MTX start until 12 months. Erythrocyte MTX-PGs with 1 to 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 one year of MTX treatment, linear regression and linear mixed model analyses were used. To determine associations of MTX-PGs with adverse effects during one 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 one year. None of the MTX-PGs was associated with adverse effects. 

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

Disclosure:

M. Bulatovic Calasan,
None;

E. den Boer,
None;

M. C. F. J. De Rotte,
None;

S. J. Vastert,
None;

S. Kamphuis,
None;

R. De Jonge,
None;

N. M. Wulffraat,
None.

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