Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long‐term methotrexate treatment

Stamp, Lisa K.; O’Donnell, John L.; Chapman, Peter T.; Zhang, Mei; Frampton, Christopher; James, Joshua I.; Barclay, Murray L.

doi:10.1002/art.24653

Cited by 94 publications

(79 citation statements)

References 29 publications

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“…Like Stamp and colleagues, we found that the dose of MTX (in mg/kg) had a better correlation with longer chain MTXGlu 3-5 compared with lower order polyglutamates, with higher doses of MTX associated with higher concentrations of the long-chain polyglutamates (results not shown). Stamp et al hypothesized that the time to reach steady state may play a part in this phenomenon, with the longer chain subtypes revealing a more apparent relationship with dose compared with the shorter chain subtypes (20).…”

Section: Discussionmentioning

confidence: 99%

Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: Effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations

Becker¹,

Haandel²,

Gaedigk³

et al. 2010

Arthritis & Rheumatism

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Objective. Intracellular methotrexate (MTX) polyglutamates (MTXGlu) have been shown to be potentially useful biomarkers of clinical response in adult patients with rheumatoid arthritis. The present study was undertaken to measure intracellular MTXGlu concentrations in a cohort of patients with juvenile idiopathic arthritis (JIA) to determine the predictors of MTXGlu variability in these patients.Methods. Blood samples were obtained from patients with JIA who were being treated with a stable dose of MTX for >3 months. Clinical data were collected by chart review. Concentrations of MTXGlu 1-7 in red blood cell lysates were quantitated using an innovative ionpairing chromatography procedure, with detection by mass spectrometry.Results

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Section: Discussionmentioning

confidence: 99%

Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: Effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations

Becker¹,

Haandel²,

Gaedigk³

et al. 2010

Arthritis & Rheumatism

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“…MTX is one of the most commonly used antirheumatic medications (21), as mono-therapy or in combination with the disease modifying drugs (LMB) because of its therapeutic efficiency and toxicity profile (6). The antiinflammatory effect of MTX is mediated by adenosine receptors stimulation (22,23) so the determination of ADA catalytic activities is significant in monitoring the metabolism and therapy effects of MTX.…”

Section: Introductionmentioning

confidence: 99%

Adenosine Deaminase Isoenzymes in the Diagnosis and Monitoring of Rheumatoid Arthritis

Nalesnik¹,

Nikolić²,

Bućma³

2012

Journal of Medical Biochemistry

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The aim of this study was determination of the cata ly tic activities of adenosine deaminase (ADA), ADA1 and ADA2 isoenzymes in the serum of patients suffering from rheumatoid arthritis (RA) who were and were not treated with methotrexate (MTX), and identification of the possibilities of using these biochemical parameters in diagnosing and monitoring the treatment effects in RA. Catalytic activities of total ADA (tADA) and ADA2 in serum were determined by a spectrophotometric method. A statistically significant correlation was found between the total ADA and ADA1 values, as well as between tADA and ADA2 in the serum of all patients suffering from RA. Determination of ADA1 and ADA2 isoenzyme catalytic activities in the serum of patients who might be suffering from RA improves the diagnostic value of total ADA catalytic activity determination. ADA2 catalytic activity in serum can be a useful biochemical marker in diagnosing and monitoring RA. Decrease in ADA1 isoenzyme catalytic activities in the serum of patients suffering from RA who were treated with MTX can help in the observation of MTX therapy effects.Kratak sadr`aj: Cilj rada bilo je odre|ivanje kataliti~kih aktiv nosti izoenzima adenozin deaminaze (ADA), ADA1 i ADA2 u serumima obolelih od reumatoidnog artritisa (RA) le~enih uz pomo} ili bez terapije metotreksatom (MTX), kao i utvr |i vanje mogu}nosti uvo|enja ovih biohemijskih parametara u dijagnostiku i pra}enje terapijskih efekata u RA. Kataliti~ke aktivnosti ukupne ADA (tADA) i ADA2 u serumima odre|i vane su spektrofotometrijskom metodom. Utvr|e na je stati sti ~ki zna~ajna korelacija izme|u kataliti~kih aktivnosti tADA i ADA1, kao i tADA i ADA2 u serumima svih ispitanika sa RA. Odre|ivanje kataliti~kih aktivnosti izoenzima ADA1 i ADA2 u serumima pacijenata sa sumnjom na RA pobolj{ava dijagnosti~ku vrednost odre|ivanja kataliti~ke aktivnosti tADA. Kata li ti ~ka aktivnost ADA2 u serumu mo`e da bude koristan bio he mijski marker u dijagnostici i pra}enju RA. Sma njenje ka ta li ti~kih aktivnosti izoenzima ADA1 u serumima pacijenata sa RA koji su dobijali MTX mo`e da pomogne u pra}enju terapijskih efekata MTX.Klju~ne re~i: izoenzimi adenozin deaminaze, metotreksat, reumatoidni artritis

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“…There is now some evidence that MTX-polyglutamate (MTX-PG) levels in patients with RA may be related to efficacy 2,3,4,5,6,7 , although not all investigators have reached the same conclusions 8 . Nevertheless, researchers are rightfully examining the factors that affect the accumulation of MTX-PG, which could lead to important insights into their contribution to the therapeutic effects of MTX.…”

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confidence: 99%

Still Trying to Understand Methotrexate

Kremer

2014

J Rheumatol

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Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long‐term methotrexate treatment

Abstract: Objective. Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) in the management of rheumatoid arthritis (RA). MTX is transported into cells

Cited by 94 publications

References 29 publications

Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: Effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations

Analysis of intracellular methotrexate polyglutamates in patients with juvenile idiopathic arthritis: Effect of route of administration on variability in intracellular methotrexate polyglutamate concentrations

Adenosine Deaminase Isoenzymes in the Diagnosis and Monitoring of Rheumatoid Arthritis

Still Trying to Understand Methotrexate

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