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

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

Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: Effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations

“…Descriptive statistics were used to characterize variability in the total intracellular MTXGlu (MTXGlu TOT ) concentrations and in the concentrations of each individual MTXGlu subtype (MTXGlu [1][2][3][4][5] Nonnormally distributed data were log-transformed when appropriate. Hierarchical clustering analyses of the data were performed as a class discovery method for subgroup analyses.…”

“…There was 40-fold interindividual Table 2). Analyses of correlations of the individual substrate concentrations of MTXGlu [1][2][3][4][5] with the MTXGlu TOT concentration revealed that the interindividual variability in the concentration of MTXGlu 3 correlated best with that of MTXGlu TOT (r ϭ 0.96, P Ͻ 0.0001).…”

“…Those MTXGlu subtypes considered to be long chain, i.e., those previously described as MTXGlu [3][4][5] (17), clustered together as a subgroup, and shorter chain MTXGlu, including native MTX (MTXGlu 1 ) and diglutamate MTX (MTXGlu 2 ), clustered together as another subgroup, as observed on hierarchical clustering analyses of MTXGlu concentrations (Figure 1). Variability in the long-chain MTXGlu 3-5 concentrations correlated [1][2][3][4][5] . Bivariable analyses revealed that the following variables were associated with the concentration of MTXGlu TOT : route of MTX administration (P ϭ 0.0002), age (P ϭ 0.004), dose of MTX (in mg/kg per week) (P Ͻ 0.0001), duration of MTX therapy (in months) (P ϭ 0.0003), and NSAID use (P ϭ 0.07).…”

“…For every patient, the concentration of each MTXGlu was also expressed as a percentage of the MTXGlu TOT for that patient ( Table 2). Proportions of the individual MTXGlu [1][2][3][4][5] relative to the total concentration were evaluated for associations with the same clinical variables as described above (results of the final multivariable linear regression analyses are available from the corresponding author upon request). Overwhelmingly, the route of MTX administration and, at times, the dose of MTX (in mg/kg) were important contributors to variability in the proportion of individual MTXGlu species, specifically with the longer chain subtypes.…”

A randomized, placebo‐controlled trial of infliximab plus methotrexate for the treatment of polyarticular‐course juvenile rheumatoid arthritis

“…Weekly methotrexate (MTX), at parenteral dosages of up to 15 mg/m 2 /week, has been established as an effective and safe therapy for polyarticular-course JRA (5)(6)(7). For children whose disease does not respond to MTX, anti-tumor necrosis factor (anti-TNF) therapy is a treatment option (8)(9)(10)(11).…”