Expression of folylpolyglutamyl synthetase predicts poor response to methotrexate therapy in patients with rheumatoid arthritis

Objective The enzyme folylpolyglutamyl synthetase (FPGS) is involved in the resistance to methotrexate in tumor cell lines. The aim of the present study was to determine the impact of FPGS mRNA expression on resistance to methotrexate therapy in patients with rheumatoid arthritis (RA). Methods We determined the expression of FPGS mRNA using the Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) in 141 patients with RA. All patients received methotrexate therapy. The primary outcome measures were disease activity as determined by a disease activity score (DAS) and response to therapy. Results Seventy-eight of 141 patients (55%) showed expression of FPGS mRNA. FPGS mRNA expression was not associated with age, sex, disease duration, white blood cell count, erythrocyte sedimentation rate, C-reactive protein (CRP), number of swollen joints, number of painful joints, and combined therapy with other disease-modifying antirheumatic drugs (DMARDs) or additional corticosteroids. The response rate to methotrexate therapy was 44% for the total study population. Patients without FPGS mRNA expression showed a significantly higher response rate than patients with FPGS mRNA expression (57% versus 33%; p = 0.005). Multi-variate logistic regression analysis revealed that female sex (p = 0.009) and FPGS mRNA expression (p = 0.004) were independent predictive factors for failure to achieve a response to methotrexate therapy. Conclusion FPGS mRNA expression is an independent predictive factor associated with poor response to methotrexate therapy in RA patients.