Journal
JOURNAL OF RHEUMATOLOGY
Volume 37, Issue 10, Pages 2180-2186Publisher
J RHEUMATOL PUBL CO
DOI: 10.3899/jrheum.091427
Keywords
JUVENILE IDIOPATHIC ARTHRITIS; METHOTREXATE; MTHFR; ERYTHROCYTE; EFFICACY; TOXICITY
Categories
Funding
- Ministry of Education [MSM 0021620820]
- Ministry of Health, Czech Republic [NE6681-3/2001]
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Objective. To investigate whether methylenetetrahydrofolate reductase (MTHFR) C677T and A 1298C polymorphisms and erythrocyte concentration of methotrexate (EMTX) could serve as predictors of methotrexate (MTX) efficacy and toxicity in patients with juvenile idiopathic arthritis (JIA). Methods. Genetic analyses and EMTX and folate assessment were performed in 69 patients with JIA aged 2.5-19.6 years (30 male) treated with MTX using a dose-escalation protocol and classified as full responders (disease inactivity; n = 51) or nonresponders (< 30% improvement in pediatric American College of Rheumatology-30 criteria while receiving >= 15 mg/m(2)/week parenteral MTX for at least 3 months; n = 18). Results. Nonresponders were treated with the higher median MTX dose (17.2 vs 12.6 mg/m(2)/week; p < 0.0001) and accumulated more EMTX (217 vs 106 nmol/l; p < 0.02) and erythrocyte folates (763 vs 592 nmol/l; p = 0.052) than responders. Analysis of MTHFR allele and genotype frequencies in relation to response failed to detect association. The frequency of any adverse effect was 29.4% in responders and 33.3% in nonresponders (p = 0.77). The frequency of 677T allele was elevated in patients with adverse effects (52.4% vs 20.9%; OR 3.88, 95% CI 1.8-8.6, p < 0.002). The probability of any adverse effect was significantly higher in patients with 677TT compared to the 677CC genotype (OR 55.5, 95% CI 2.9-1080, p < 0.001). Conclusion. MTHFR genotyping, may have a predictive value for the risk of MTX-associated toxicity in patients with JIA. Despite the lack of therapeutic effect, nonresponders accumulated adequate concentrations of EMTX. (First Release July 1 2010; J Rheumatol 2010;37:2180-6; doi:10.3899/jrheum.091427)
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