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

• Published in: Pharmacogenomics Vol. 13; no. 9; pp. 1087 - 1094
• Main Authors: Fransen, Jaap, Kooloos, Wouter M, Wessels, Judith AM, Huizinga, Tom WJ, Guchelaar, Henk-Jan, van Riel, Piet LCM, Barrera, Pilar
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.07.2012
• Subjects: Adult; AMP Deaminase - genetics; Antirheumatic Agents - administration & dosage; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - pathology; Biomarkers, Pharmacological; Data processing; DNA; Dosage and administration; Drug metabolism; Drug therapy; Drugs; effectiveness of therapy; Female; Gene polymorphism; Genetic aspects; Humans; Hydroxymethyl and Formyl Transferases - genetics; Male; Methotrexate; Methotrexate - administration & dosage; Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics; Middle Aged; Minor Histocompatibility Antigens; Multienzyme Complexes - genetics; Nucleotide Deaminases - genetics; pharmacogenetic models; Pharmacogenetics; Pharmacology, Experimental; Precision Medicine; prediction models; Pyrophosphatases - genetics; Rheumatoid arthritis; Treatment Outcome
• ISSN: 1462-2416; 1744-8042
• DOI: 10.2217/pgs.12.83

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. 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 , , and . 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). 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. Original submitted 17 February 2012; Revision submitted 10 May 2012