May 29, 2007

A clinical pharmacogenetic model to predict the efficacy of methotrexate monotherapy in recent-onset rheumatoid arthritis

Arthritis and Rheumatism
Judith A M WesselsPharmacogenetics Collaborative Research Group

Abstract

To develop a clinical pharmacogenetic model to predict the efficacy of methotrexate (MTX) in rheumatoid arthritis (RA). Two hundred five patients with newly diagnosed RA and active disease were treated with MTX (initiated at a dosage of 7.5 mg/week and increased to 15 mg/week after 4 weeks) and folic acid (1 mg/day). If the Disease Activity Score (DAS) was >2.4 at 3 months, the dosage of MTX was increased up to 25 mg/week. Twenty-four baseline variables possibly influencing disease state and drug response were selected. In addition, 17 polymorphisms in 13 genes related to the MTX mechanism of action, purine and pyrimidine synthesis, were determined. Factors were compared between responders (defined as patients with a DAS < or = 2.4 at 6 months) and nonresponders. In case of differences, a stepwise selection procedure identified the predictors for response. A clinical score was designed by simplifying regression coefficients of the independent variables. Cutoff levels were chosen based on the clinical score, and positive and negative response rates were calculated. An evaluation of the model was performed in a second group of patients. The model for MTX efficacy consisted of sex, rheumatoid factor and smoking status, the DAS, an...Continue Reading

  • References55
  • Citations116

References

  • References55
  • Citations116

Citations

Mentioned in this Paper

Drug Response
Pyrophosphatase
ATIC protein, human
Antirheumatic Drugs, Disease-Modifying
Hydroxymethyl and Formyl Transferases
Pharmacogenetics
Rheumatoid Arthritis
C-1-Tetrahydrofolate Synthase, Cytoplasmic
AMP Deaminase
Nucleotide Deaminases

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