Dose escalation of parenteral methotrexate in active rheumatoid arthritis that has been unresponsive to conventional doses of methotrexate: A randomized, controlled trial

Abstract

Results. Sixty-four patients were eligible for entry and were switched from oral MTX to 15 mg/week IM MTX. At baseline, the mean ؎ SD DAS28 was 5.6 ؎ 0.88; after 6 weeks of IM MTX, the DAS28 had improved by a mean of 0.42 (95% confidence interval [95% CI] 0.15-0.69). At 6 weeks, 54 patients still had a DAS28 of >3.2 and were therefore eligible for randomization. By 22 weeks, 1 patient (3.7%) in each group achieved the primary outcome of a DAS28 <3.2 (95% CI for the difference between the groups ؊15% to ؉15%). Five patients (18.5%) in each group showed an improvement of >1.2 in the DAS28 (95% CI for the difference between the groups ؊18% to ؉18%). One patient (3.7%) in each group achieved an ACR20 response, but none achieved a good response as defined by the EULAR response criteria. One patient in each group had a serious adverse reaction; minor adverse reactions were more frequently reported in the dose escalation group.Conclusion. Switching from oral to parenteral MTX 15 mg/week results in a minor improvement in disease control. For patients with active RA receiving 15

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

“…On the contrary, our study shows that doubling the dosage of MTX from 15 mg/m 2 /week to 30 mg/m 2 /week in JIA does not lead to any further significant clinical improvement, and therefore the plateau of efficacy of MTX is reached with the parenteral administration of 15 mg/m 2 /week. Similar results have been obtained recently in a preliminary study involving adult rheumatoid arthritis (37).…”

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.…”