Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis
| Autor: | Robert de Jonge, Johanna M. W. Hazes, Ethan den Boer, Maja Bulatović Ćalasan, Andreas H. Gerards, Maurits C F J de Rotte, Pascal H P de Jong, Barbara van Schaeybroeck, Saskia M F Pluijm, Angelique E. A. M. Weel, Nico M Wulffraat, A Margriet Huisman, Jan Lindemans |
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| Přispěvatelé: | Clinical Chemistry, Rheumatology, Pediatrics, CCA - Disease profiling, ICaR - Circulation and metabolism, NCA - Brain mechanisms in health and disease, NCA - neurodegeneration |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Longitudinal study PHARMACOKINETICS Erythrocytes THERAPY Arthritis Rheumatoid Cohort Studies Tandem Mass Spectrometry immune system diseases Epidemiology Immunology and Allergy Medicine CRITERIA heterocyclic compounds Longitudinal Studies skin and connective tissue diseases Non-U.S. Gov't medicine.diagnostic_test CORRELATE Research Support Non-U.S. Gov't FOLATE PATHWAY PULSE METHOTREXATE Middle Aged Connective tissue disease Polyglutamic Acid Antirheumatic Agents Rheumatoid arthritis Female medicine.drug musculoskeletal diseases medicine.medical_specialty Immunology AMERICAN-COLLEGE Research Support General Biochemistry Genetics and Molecular Biology VALIDATION Rheumatology Pharmacokinetics Internal medicine Journal Article Humans Adverse effect CLINICAL-EFFICACY POLYMORPHISMS business.industry medicine.disease Surgery Methotrexate Therapeutic drug monitoring business Chromatography Liquid |
| Zdroj: | Annals of the Rheumatic Diseases, 74(2), 408. BMJ Publishing Group De Rotte, M C F J, Den Boer, E, De Jong, P H P, Pluijm, S M F, Bulatović Ćalasan, M, Weel, A E, Huisman, A M, Gerards, A H, Van Schaeybroeck, B, Wulffraat, N M, Lindemans, J, Hazes, J M W & De Jonge, R 2015, ' Methotrexate polyglutamates in erythrocytes are associated with lower disease activity in patients with rheumatoid arthritis ', Annals of the Rheumatic Diseases, vol. 74, no. 2, pp. 408-414 . https://doi.org/10.1136/annrheumdis-2013-203725 Annals of the Rheumatic Diseases, 74(2), 408-414. BMJ Publishing Group |
| ISSN: | 0003-4967 |
| DOI: | 10.1136/annrheumdis-2013-203725 |
| Popis: | 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 (β=-0.007) and total MTX-PG (ß=-0.004) were associated (pCONCLUSIONS: 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. |
| Databáze: | OpenAIRE |
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