title: Clinical pharmacogenetic model to predict response of MTX monotherapy in patients with established rheumatoid arthritis after DMARD failure.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Radboud University Nijmegen Medical Center, PO Box 9101, 6500HB Nijmegen, The Netherlands.
authors: Jaap
authors: J
authors: Fransen
authors: Wouter M
authors: WM
authors: Kooloos
authors: Judith A M
authors: JA
authors: Wessels
authors: Tom W J
authors: TW
authors: Huizinga
authors: Henk-Jan
authors: HJ
authors: Guchelaar
authors: Piet L C M
authors: PL
authors: van Riel
authors: Pilar
authors: P
authors: Barrera
mesh_terms: D000659:AMP Deaminase / Q000235:genetics; D000328:Adult; D018501:Antirheumatic Agents / Q000008:administration & dosage*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D054316:Biomarkers, Pharmacological; D005260:Female; D006801:Humans; D019877:Hydroxymethyl and Formyl Transferases / Q000235:genetics; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens; D009097:Multienzyme Complexes / Q000235:genetics; D009709:Nucleotide Deaminases / Q000235:genetics; D057285:Precision Medicine; D011755:Pyrophosphatases / Q000235:genetics; D016896:Treatment Outcome; D000097630:Inosine Triphosphatase
chemical_list: D000659:AMP Deaminase; D018501:Antirheumatic Agents; D054316:Biomarkers, Pharmacological; D019877:Hydroxymethyl and Formyl Transferases; D008727:Methotrexate; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D015778:Minor Histocompatibility Antigens; D009097:Multienzyme Complexes; D009709:Nucleotide Deaminases; D011755:Pyrophosphatases; C113120:inosine monophosphate synthase; C539735:MTHFD1 protein, human; C514117:AMPD1 protein, human; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase