title: Prediction of clinical non-response to methotrexate treatment in juvenile idiopathic arthritis.
abstract: OBJECTIVE
  Methotrexate (MTX) is a cheap and efficacious 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 first year of treatment. Non-response to MTX was defined 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 transformed into a total risk score (range 0-11). At a cut-off of ≥3, sensitivity was 78%, specificity 49%, positive predictive value was 83% and negative predictive value 41%.
  
  
  CONCLUSIONS
  The prediction model that we developed and validated combines clinical and genetic variables to identify JIA patients not responding to MTX treatment. This model could assist clinicians in making individualised treatment decisions.
authors.affiliation: University Medical Center Utrecht, Wilhelmina Children's Hospital, Department of Pediatric Immunology, 3508AB Utrecht, The Netherlands. m.bulatovic@umcutrecht.nl
authors.forename: Maja
authors.initials: M
authors.lastname: Bulatovic
authors.forename: Marloes W
authors.initials: MW
authors.lastname: Heijstek
authors.forename: E H Pieter
authors.initials: EH
authors.lastname: Van Dijkhuizen
authors.forename: Nico M
authors.initials: NM
authors.lastname: Wulffraat
authors.forename: Saskia M F
authors.initials: SM
authors.lastname: Pluijm
authors.forename: Robert
authors.initials: R
authors.lastname: de Jonge
mesh_terms: D000293:Adolescent; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D015233:Models, Statistical; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate