2013-10-02
Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis
Publication
Publication
Objective: To investigate if erythrocyte-methotrexate-polyglutamate (MTX-PG) concentrations in patients with rheumatoid arthritis (RA) are associated with disease activity or adverse events. Methods: We used a longitudinal study design with two cohorts. The derivation cohort included 102 and the validation cohort included 285 patients with RA on MTX. We measured erythrocyte-MTX-PG with 1-5 glutamate residues at 3 months, 6 months and 9 months after MTX start with a liquid chromatography (LC)-mass spectrometry (MS)/MS assay. Outcomes were disease activity score in 28 joints (DAS28) and adverse events. Longitudinal associations of MTX-PG concentrations after 3 months, 6 months and 9 months with DAS28 were tested with a linear mixed model adjusted for age, gender, baseline DAS28, MTX dose and comedication. Results: In the derivation cohort, mean DAS28 decreased from 4.26 (SE=0.14) at baseline to 2.72 (SE=0.13) after 9 months. Thirty per cent of patients in the derivation cohort experienced more than three adverse events after 3 months, which decreased to 18% after 9 months. In the validation cohort, DAS28 and adverse events were comparable with the derivation cohort. In the derivation cohort, MTX-PG1 (ß=-0.005), MTX-PG2 (ß=-0.022), MTX-PG3 (ß=-0.007) and total MTX-PG (ß=-0.004) were associated (p<0.05) with lower DAS28 over 9 months. In the validation cohort, MTX-PG2 (ß=-0.015), MTX-PG3 (ß=-0.010), MTX-PG4 (ß=-0.008) and total MTX-PG (ß=-0.003) were associated with lower DAS28 over 9 months. None of the MTX-PGs was associated with adverse events. Conclusions: In this first longitudinal study, we showed that an increase in erythrocyte-MTX-PG concentration was associated with a decreased DAS28 over 9 months in two cohorts, and is therefore a potential tool for therapeutic drug monitoring of MTX in RA.
Additional Metadata | |
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doi.org/10.1136/annrheumdis-2013-203725, hdl.handle.net/1765/55171 | |
Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases | |
Organisation | Department of Clinical Chemistry |
de Rotte, M., den Boer, E., de Jong, P., Pluijm, S., Bulatović Ćalasan, M., Weel, A., … de Jonge, R. (2013). Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis. Annals of the Rheumatic Diseases: an international peer-reviewed journal for health professionals and researchers in the rheumatic diseases. doi:10.1136/annrheumdis-2013-203725 |