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.
M. Bulatovic Calasan,
E. den Boer,
M. C. F. J. De Rotte,
S. J. Vastert,
R. De Jonge,
N. M. Wulffraat,
« Back to 2013 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/methotrexate-polyglutamates-in-erythrocytes-are-associated-with-lower-disease-activity-in-juvenile-idiopathic-arthritis-patients/