Methotrexate polyglutamate concentrations are not associated with disease control in rheumatoid arthritis patients receiving long-term methotrexate therapy.
ABSTRACT 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.
- SourceAvailable from: Piet van Riel[show abstract] [hide abstract]
ABSTRACT: Objective. The development and validation of Modified Disease Activity Scores (DAS) that include different 28-joint counts.Methods. These scores were developed by canonical discriminant analyses and validated for criterion, correlational, and construct validity. The influence of disease duration on the composition of the DAS was also investigated.Results. No influence of disease duration was found. The Modified DAS that included 28-joint counts were able to discriminate between high and low disease activity (as indicated by clinical decisions of rheumatologists).Conclusion. The Modified DAS are as valid as disease activity scores that include more comprehensive joint counts.Arthritis & Rheumatism 12/1994; 38(1):44 - 48. · 7.48 Impact Factor
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ABSTRACT: Rheumatoid arthritis (RA) is a systemic inflammatory arthritis that can not only result in permanent joint damage, but is associated with high morbidity and mortality. Disease-modifying antirheumatic drugs (DMARDs) are the mainstay of treatment in RA. DMARDs improve the symptoms of joint pain and swelling, but more importantly, prevent the progression of joint damage. Methotrexate (MTX) is the first-line DMARD in RA with over two decades worth of excellent long-term efficacy and safety. However, there is significant variability in patients' response to MTX, both in efficacy and toxicity. Recent advances in genetics, particularly pharmacogenetics, may permit the prediction, a priori, of an individual patient's response to MTX. In this review, we highlight recent published literature on the pharmacogenetics of MTX in RA. Pharmacogenetics may be a useful means of optimising MTX therapy in patients with RA.Clinical and experimental rheumatology 01/2008; 28(5 Suppl 61):S33-9. · 2.66 Impact Factor
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ABSTRACT: Liver tissue from 16 patients with rheumatoid arthritis was studied. The patients had received low dose methotrexate weekly for a minimum of 12 months between two liver biopsies. The progression of pericellular fibrosis was measured by computerised image analysis. Extracts of these liver biopsy specimens were pooled into five samples according to the progression of hepatic fibrosis and analysed by high performance liquid chromatography. The concentrations of methotrexate, 2,4 diamino-N(10)-methylpteroic acid, and methotrexate polyglutamate were markedly increased in the samples obtained from the three patients who recorded the greatest increase in fibrosis. These preliminary data suggest that progression of hepatic fibrosis is related to the retention of methotrexate and metabolites in the liver.Annals of the Rheumatic Diseases 08/1991; 50(7):477-80. · 9.11 Impact Factor