title: A randomized trial of parenteral methotrexate comparing an intermediate dose with a higher dose in children with juvenile idiopathic arthritis who failed to respond to standard doses of methotrexate.
abstract: OBJECTIVE
  To compare the safety and efficacy of parenteral methotrexate (MTX) at an intermediate dosage (15 mg/m(2)/week) versus a higher dosage (30 mg/m(2)/week) in patients with polyarticular-course juvenile idiopathic arthritis (JIA) who failed to improve while receiving standard dosages of MTX (8-12.5 mg/m(2)/week).
  
  
  METHODS
  In the screening phase, 595 patients who were newly started on a standard dose of MTX were followed up for 6 months. Subsequently, the nonresponders, defined according to the American College of Rheumatology (ACR) pediatric 30% improvement criteria (pediatric 30), were randomized to receive an intermediate dose or higher dose of parenteral MTX for an additional 6 months. Improvement in the screening and randomization phase was defined by the ACR pediatric 30 response, as well as by the 50% and 70% response levels (ACR pediatric 50 and ACR pediatric 70, respectively).
  
  
  RESULTS
  In the screening phase, after receiving standard doses of MTX, 430 patients (72%) improved according to the ACR pediatric 30, while 360 (61%) met the ACR pediatric 50 and 225 (38%) met the ACR pediatric 70; among these patients, 69 (12%) also met the definition of complete disease control. Of the 133 nonresponders, 80 were randomized to receive an intermediate dose or higher dose of MTX. In the randomization phase, the ACR pediatric 30 response rate was 25 of 40 children (62.5%) in the intermediate-dose group versus 23 of 40 children (57.5%) in the higher-dose group. An ACR pediatric 50 response rate was attained by 23 patients (57.5%) receiving an intermediate dose versus 22 (55%) in the higher-dose group. An ACR pediatric 70 response rate was seen in 18 children (45%) receiving an intermediate dose versus 19 (47.5%) receiving a higher dose. Five children (12.5%) in the intermediate-dose group versus 4 (10%) receiving the higher dose of MTX also met the definition of complete disease control. None of the intergroup differences in response rate were significant. There were no significant differences in the frequency of adverse events or laboratory abnormalities between the 2 randomized groups.
  
  
  CONCLUSIONS
  This study shows that the plateau of efficacy of MTX in JIA is reached with parenteral administration of 15 mg/m(2)/week and that a further increase in dosage is not associated with any additional therapeutic benefit. MTX should be administered for up to 9-12 months to appreciate its full therapeutic effect.
authors.affiliation: IRCCS G. Gaslini, University of Genoa, Genoa, Italy. nicolaruperto@ospedale-gaslini.ge.it
authors.forename: Nicolino
authors.initials: N
authors.lastname: Ruperto
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Murray
authors.forename: Valeria
authors.initials: V
authors.lastname: Gerloni
authors.forename: Nico
authors.initials: N
authors.lastname: Wulffraat
authors.forename: Sheila Knupp Feitosa
authors.initials: SK
authors.lastname: de Oliveira
authors.forename: Fernanda
authors.initials: F
authors.lastname: Falcini
authors.forename: Pavla
authors.initials: P
authors.lastname: Dolezalova
authors.forename: Maria
authors.initials: M
authors.lastname: Alessio
authors.forename: Ruben
authors.initials: R
authors.lastname: Burgos-Vargas
authors.forename: Fabrizia
authors.initials: F
authors.lastname: Corona
authors.forename: Richard
authors.initials: R
authors.lastname: Vesely
authors.forename: Helen
authors.initials: H
authors.lastname: Foster
authors.forename: Joyce
authors.initials: J
authors.lastname: Davidson
authors.forename: Francesco
authors.initials: F
authors.lastname: Zulian
authors.forename: Line
authors.initials: L
authors.lastname: Asplin
authors.forename: Eileen
authors.initials: E
authors.lastname: Baildam
authors.forename: Julia Garcia
authors.initials: JG
authors.lastname: Consuegra
authors.forename: Huri
authors.initials: H
authors.lastname: Ozdogan
authors.forename: Rotraud
authors.initials: R
authors.lastname: Saurenmann
authors.forename: Rik
authors.initials: R
authors.lastname: Joos
authors.forename: Angela
authors.initials: A
authors.lastname: Pistorio
authors.forename: Pat
authors.initials: P
authors.lastname: Woo
authors.forename: Alberto
authors.initials: A
authors.lastname: Martini
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001171:Arthritis, Juvenile / Q000188:drug therapy*; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate