Abstract
Abstract
Background
Methotrexate is an immunomodulatory drug for patients with Crohn’s disease. Erythrocyte MTX-polyglutamates (MTX-PG1-5) may be used for therapeutic drug monitoring (TDM) as MTX-PG is thought to mediate MTX’s efficacy. Information on determinants of the concentration of MTX-PG in patients with Crohn’s disease is lacking. We aim to identify clinical and biochemical determinants of the erythrocyte MTX-PG1-5 and MTX-PGtotal concentration in patients with Crohn’s disease.
Methods
Adults with Crohn’s disease on methotrexate treatment who visited the outpatient clinic of Amsterdam UMC were included. Erythrocyte MTX-PGs were measured by tandem mass spectrometry.
Results
Nineteen patients were included, with a median duration of MTX use of 77 months (range 7–202). Twelve patients received MTX monotherapy, whereas 7 patients were on concomitant TNF-α inhibitors. The mean dose of MTX was 15.5 mg (SD ± 2.8) and 12 (63%) patients used subcutaneous MTX. MTX-PG1-5 were successfully measured in 18 patients, showing substantial variability in concentrations of MTX-PGtotal and individual species. The median MTX-PGtotal was 117.1 nmol/L (range 46.4–258.7) with preferential accumulation of MTX-PG3 (43.1 nmol/L, range 15.3–96.1). Patients on subcutaneous compared to oral MTX had higher median MTX-PG(4,5) levels (55 versus 9 nmol/L, p = 0.01). Higher age (β = 0.71) and lower estimated glomerular filtration rate (β = − 0.52) were associated with a significantly higher MTX-PGtotal concentration (R2 = 0.60, p = 0.001).
Conclusion
MTX-PG concentrations display a considerable inter-individual variability. Higher MTX-PG accumulation is associated with subcutaneous administration, higher age, and lower renal function in Crohn’s disease patients.
Funder
Dutch Initiative on Crohn’s and Colitis
Maag Lever Darm Stichting
Publisher
Springer Science and Business Media LLC
Subject
Gastroenterology,General Medicine
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