19 research outputs found
Methotrexate efficacy, but not its intolerance, is associated with the dose and route of administration
What Is the Persistence to Methotrexate in Rheumatoid Arthritis, and Does Machine Learning Outperform Hypothesis‐Based Approaches to Its Prediction?
Folylpolyglutamate synthase is a major determinant of intracellular methotrexate polyglutamates in patients with rheumatoid arthritis
Methotrexate polyglutamate levels and co-distributions in childhood acute lymphoblastic leukemia maintenance therapy
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Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.
Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.The Pharmacogenomics Journal advance online publication, 8 April 2014; doi:10.1038/tpj.2014.3