Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy

Abstract

Objective. There are limited data suggesting that methotrexate polyglutamate (MTXGlu) concentrations can guide MTX dosing in patients with rheumatoid arthritis (RA). The aim of this study was to define a therapeutic range of red blood cell (RBC) MTXGlun concentrations (where n refers to the number of glutamate groups), including threshold values for efficacy and adverse effects in patients receiving long-term oral MTX treatment. Methods. A cross-sectional study of 192 patients receiving oral MTX was undertaken. Disease activity was assessed by the swollen and tender joint counts, the C-reactive protein level, and the Disease Activity Score in 28 joints (DAS28). High disease activity was defined as a DAS28 of >3.2. A standardized questionnaire regarding common MTX adverse effects was completed. Results. The MTX dosage was significantly higher in patients in whom the swollen joint count and DAS28 were higher. The MTXGlu4, MTXGlu5, MTXGlu3-5, and MTXGlu1-5 concentrations were significantly higher in patients with high disease activity. After correction for age, the estimated glomerular filtration rate, and the MTX dosage, the association remained significant for MTXGlu5• RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlun concentration and adverse effects. Conclusion. In contrast to other studies, the results of the present study did not show a relationship between the MTXGlun concentration and reduced disease activity in patients with RA who were receiving long-term MTX therapy. However, disease activity was influenced by the RBC folate level, which may be a more important factor than MTXGlun concentrations for disease control. In accordance with the findings of previous studies, we were unable to show a relationship between MTXGlun concentrations and adverse effects. Prospective studies will be important to determine whether there is a role for measuring MTXGlun concentrations in patients receiving long-term treatment with MTX. © 2010, American College of Rheumatology.