Monitoring methotrexate toxicity in juvenile idiopathic arthritis

To determine the frequency of laboratory abnormalities with methotrexate (MTX) use in patients with juvenile idiopathic arthritis (JIA); to identify potential risk factors for MTX toxicity requiring medical interventions; and to compare the frequency of liver function abnormalities in patients treated with MTX to those not treated with MTX.

Results of MTX surveillance laboratory testing (SLT) available in clinical databases were reviewed for 588 children with JIA. Information on demographics, JIA features, and factors previously associated with increased frequency of SLT abnormalities was obtained.

Results of SLT performed in at least 4-month intervals were available for 138 JIA patients whose JIA was not treated with MTX, and for 198 JIA patients treated with MTX plus folic acid. On SLT of the MTX-treated patients, there were 44 of 2650 (1.7%) AST tests and 90 of 2647 (3.4%) ALT tests that exceeded 2 times the upper limit of normal (> 2 ULN) in 30 children (15%). AST or ALT tests at > 2 ULN occurred more often with systemic JIA (p = 0.04), macrophage activation syndrome, during infections, in systemic antibiotic use, and after intensifying JIA drug regimens. AST or ALT results at > 2 ULN were as frequent among MTX-treated children as those not treated with MTX. Renal and hematological abnormalities with MTX were uncommon.

Liver enzyme abnormalities > 2 ULN are rare in JIA, irrespective of MTX exposure. These data suggest that the adult standard of SLT every 4-8 weeks may not be necessary in children treated with MTX, especially if certain risk factors are absent.