RT Journal Article
SR Electronic
T1 Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in juvenile idiopathic arthritis patients
JF Annals of the Rheumatic Diseases
JO Ann Rheum Dis
FD BMJ Publishing Group Ltd and European League Against Rheumatism
SP 402
OP 407
DO 10.1136/annrheumdis-2013-203723
VO 74
IS 2
A1 Bulatović Ćalasan, Maja
A1 den Boer, Ethan
A1 de Rotte, Maurits C F J
A1 Vastert, Sebastiaan J
A1 Kamphuis, Sylvia
A1 de Jonge, Robert
A1 Wulffraat, Nico M
YR 2015
UL http://ard.bmj.com/content/74/2/402.abstract
AB 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.