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

Annals of Rheumatic Diseases, 05/25/2012

Bulatovic M et al. – The prediction model that the authors developed and validated combines clinical and genetic variables to identify juvenile idiopathic arthritis (JIA) patients not responding to Methotrexate (MTX) treatment. This model could assist clinicians in making individualised treatment decisions.

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%.

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