Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis

Objectives Methotrexate (MTX) is a cheap and effi cacious drug in juvenile idiopathic arthritis (JIA) treatment. If JIA patients are unresponsive to MTX, early and effective combination treatment with biologicals is required to prevent joint damage. The authors developed a prediction model to identify JIA patients not responding to MTX. Methods In a cohort of 183 JIA patients, clinical variables and single nucleotide polymorphisms (SNPs) in genes involved in the mechanism of action of MTX were determined at the start of MTX treatment. These variables were used to construct a prediction model for non-response to MTX treatment during the fi rst year of treatment. Non-response to MTX was defi ned according the American College of Rheumatology paediatric 70 criteria. The prediction model was validated in a cohort of 104 JIA patients. Results The prediction model included: erythrocyte sedimentation rate and SNPs in genes coding for methionine synthase reductase, multidrug resistance 1 (MDR-1/ABCB1), multidrug resistance protein 1 (MRP-1/ABCC1) and proton-coupled folate transporter (PCFT). The area under the receiver operating characteristics curve (AUC) was 0.72 (95% CI: 0.63 to 0.81). In the validation cohort, the AUC was 0.65 (95% CI: 0.54 to 0.77). The prediction model was tra