title: Effectiveness and toxicity of methotrexate in juvenile idiopathic arthritis: comparison of 2 initial dosing regimens.
abstract: OBJECTIVE
  To compare the incidence of liver toxicity and clinical response between 2 initial dosing regimens of methotrexate (MTX) for treatment of juvenile idiopathic arthritis (JIA).
  
  
  METHODS
  Clinical and laboratory data were abstracted from the medical records of 220 children newly prescribed MTX from the same geographic region. One cohort received initial doses of MTX > 0.5 mg/kg/week ("high-dose") and one cohort received initial doses of MTX <or= 0.5 mg/kg/week ("low-dose"). Toxicity was defined as aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) above the normal range, and positive clinical response was defined as a reduction in active joint count during the first 6 months of MTX therapy.
  
  
  RESULTS
  One hundred twenty-six children were in the high-dose MTX group, 94 in the low-dose MTX group. At 6 months, the high-dose group was more likely to have an elevated AST or ALT (adjusted OR 3.89, 95% CI 1.82-8.29, p < 0.0001). Subjects receiving both MTX and nonsteroidal antiinflammatory drugs (NSAID) had no significant difference between groups in change of active joint count, while subjects in the high-dose group but not taking NSAID had more active joints (p = 0.036) at 6 months compared to the low-dose group.
  
  
  CONCLUSIONS
  Initial high-dose MTX was associated with an increased risk of at least one liver enzyme abnormality with no significant improvement in active joint count. This suggests that there is no apparent benefit, while the potential for liver toxicity is increased, when using higher doses of MTX at treatment inception in patients with JIA.
authors.affiliation: Section of Rheumatology, Department of Pediatrics, Children's Mercy Hospitals and Clinics, Kansas City, Missouri 64108, USA. mlbecker@cmh.edu
authors.forename: Mara L
authors.initials: ML
authors.lastname: Becker
authors.forename: Carlos D
authors.initials: CD
authors.lastname: Rosé
authors.forename: Randy Q
authors.initials: RQ
authors.lastname: Cron
authors.forename: David D
authors.initials: DD
authors.lastname: Sherry
authors.forename: Warren B
authors.initials: WB
authors.lastname: Bilker
authors.forename: Ebbing
authors.initials: E
authors.lastname: Lautenbach
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000009:adverse effects; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D008499:Medical Records; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D018579:Patient Selection; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate