{Reference Type}: Journal Article
{Title}: Methotrexate accumulation in target intestinal mucosa and white blood cells differs from non-target red blood cells of patients with Crohn's disease.
{Author}: van de Meeberg MM;Sundaresan J;Lin M;Jansen G;Struys EA;Fidder HH;Oldenburg B;Mares WGN;Mahmmod N;van Asseldonk DP;Rietdijk ST;Nissen LHC;de Boer NKH;Bouma G;Ćalasan MB;de Jonge R; ;
{Journal}: Basic Clin Pharmacol Toxicol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jul 8
{Factor}: 3.688
{DOI}: 10.1111/bcpt.14047
{Abstract}: <B>BACKGROUND: </B>Intracellular methotrexate polyglutamates (MTX-PGs) concentrations are measurable in red blood cells (RBCs) during MTX treatment. MTX-PG3 concentrations correlate with efficacy in patients with Crohn's disease (CD). Since RBCs are not involved in pathogenesis of CD and lack extended MTX metabolism, we determined MTX-PGs accumulation in peripheral blood mononuclear cells (PBMCs: effector cells) and intestinal mucosa (target cells) and compared those with RBCs as a potential more precise biomarker.<BR><B>METHODS: </B>In a multicentre prospective cohort study, blood samples of patients with CD were collected during the first year of MTX therapy. Mucosal biopsies were obtained from non-inflamed rectum and/or inflamed intestine. MTX-PGs concentrations in mucosa, PBMCs and RBCs were measured by liquid chromatography-tandem mass spectrometry.<BR><B>RESULTS: </B>From 80 patients with CD, a total of 27 mucosal biopsies, 9 PBMC and 212 RBC samples were collected. From 12 weeks of MTX therapy onwards, MTX-PG3 was the most predominant species (33%) in RBCs. In PBMCs, the distribution was skewed towards MTX-PG1 (48%), which accounted for an 18 times higher concentration than in RBCs. Long-chain MTX-PGs were highly present in mucosa: 21% of MTX-PGtotal was MTX-PG5. MTX-PG6 was measurable in all biopsies.<BR><B>CONCLUSIONS: </B>MTX-PG patterns differ between mucosa, PBMCs and RBCs of patients with CD.