Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure

Background: The performance of a clinical pharmacogenetic model to predict nonresponse of methotrexate (MTX) monotherapy in patients with established rheumatoid arthritis (RA) and failure of disease-modifying antirheumatic drugs (DMARDs) was studied. Methods: For 75 RA patients receiving MTX monotherapy for 6 months, DNA and clinical data were available. Risk scores for nonresponse at 6 months (disease activity score >2.4), were calculated using the pharmacogenetic prediction model utilizing four clinical factors and four polymorphisms in the genes MTHFD1, AMPD1, ITPA and ATIC. Results: At 6 months, there were 25 responders and 50 nonresponders. Using the clinical pharmacogenetic prediction model, 75% (56 out of 75) were categorized into predicted responders (risk score <= 3.5) and predicted nonresponders (risk score >= 6). At 6 months, the negative predictive value was 81% (21 out of 26) and the positive predictive value was 47% (14 out of 30). Conclusion: The pharmacogenetic model predicts nonresponse to MTX monotherapy, but performs better in DMARD naive recent-onset RA patients than in patients with preceding DMARD failure.