Methotrexate Polyglutamate Concentrations Are Not Associated With Disease Control in Rheumatoid Arthritis Patients Receiving Long-Term Methotrexate Therapy

University of Otago, Christchurch, New Zealand.
Arthritis & Rheumatology (Impact Factor: 7.76). 02/2010; 62(2):359-68. DOI: 10.1002/art.27201
Source: PubMed


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) MTXGlu(n) 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.
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.
The MTX dosage was significantly higher in patients in whom the swollen joint count and DAS28 were higher. The MTXGlu(4), MTXGlu(5), MTXGlu(3-5), and MTXGlu(1-5) 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 MTXGlu(5). RBC folate concentrations were significantly higher in the group with high disease activity. There was no association between any MTXGlu(n) concentration and adverse effects.
In contrast to other studies, the results of the present study did not show a relationship between the MTXGlu(n) 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 MTXGlu(n) concentrations for disease control. In accordance with the findings of previous studies, we were unable to show a relationship between MTXGlu(n) concentrations and adverse effects. Prospective studies will be important to determine whether there is a role for measuring MTXGlu(n) concentrations in patients receiving long-term treatment with MTX.

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Available from: Murray L Barclay, Sep 25, 2014
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    • "Smoking and folate levels also affect MTX-PGs concentrations in red blood cells. They also tried to define a therapeutic range of red blood cell MTX-PGs concentrations, including threshold values for efficacy and adverse effects in patients receiving long-term oral MTX treatment in patients with RA, and reported that there was no relationship between MTX-PGs concentrations and adverse effects [162]. Dervieux et al. [163] measured red blood cell MTX-PGs concentrations in adult RA patients, and reported that the selective emergence of long-chain MTX-PGs is function of dose, time of exposure and hence dosage intensity, and concluded that switching from oral to parenteral MTX produces a selective accumulation of longer chain MTX-PGs that are known to be more potent inhibitors of de novo purine biosynthesis than shorter chain MTX-PGs. "
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