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KMID : 0388220120190010011
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Journal of the Korean Rheumatism Association
2012 Volume.19 No. 1 p.11 ~ p.18
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Hidden Questions on Methotrexate
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Lee Sang-Won
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Abstract
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Since the 1950’s, methotrexatehas been the most widely used for the treatment of rheumatoid arthritis among various disease-modifying anti-rheumatic drugs (DMARDs). In this review, several hidden questions on methotrexate were discussed. First, so far, methotrexate has been considered to improve rheumatoid arthritis by inhibiting cell proliferation through the reduction of synthesis regarding purine and pyrimidine. Recently, a new concept was proposed that methotrexate could increase the release of adenosine, which subsequently decreases the inflammatory function of immune cells, and can finally quench the inflammation in affected joints of rheumatoid arthritis. Second, there were only three clinical trials done to directly compare the efficacy between methotrexate and biologics. With these results, methotrexate showed comparable therapeutic efficacy to biologics, but did not prevent radiological progression. In the future, clinical trials to directly compare the efficacy of methotrexate to biologics will be needed. Third, measuring the serum concentration of methotrexate is not appropriate, since circulating methotrexate is rapidly cleared by cellular uptake or renal excretion. Methotrexate polyglutamate is a more stable compound than methotrexate and it is more likely to relate to efficacy or adverse effects of methotrexate. Recently, the efforts to measure methotrexate polyglutamate in red blood cells have been done to increase therapeutic efficacy and reduce its adverse effects. Fourth, NSAIDs can decrease the excretion of methotrexate though renal tubular cells and it may increase the serum concentration of methotrexate and the risk of its toxicity, suggesting that physicians should pay close attention to dose adjustments concerning methotrexate combined with NSAIDs.
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KEYWORD
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Methotrexate, Action mechanism, Biologics, Polyglutamation, NSAIDs
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