RT Journal Article
SR Electronic
T1 Patients with Rheumatoid Arthritis Treated with Methotrexate (MTX): Concentrations of Steady-state Erythrocyte MTX Correlate to Plasma Concentrations and Clinical Efficacy
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 1709
OP 1715
VO 35
IS 9
A1 NETE HORNUNG
A1 TORKELL ELLINGSEN
A1 JØRN ATTERMANN
A1 KRISTIAN STENGAARD-PEDERSEN
A1 JØRGEN HJELM POULSEN
YR 2008
UL http://www.jrheum.org/content/35/9/1709.abstract
AB Objective To investigate the accumulation of methotrexate (MTX) in circulating erythrocytes and the association with pharmacokinetic variables, weekly dose, and clinical efficacy in 2 cohorts of patients with chronic active rheumatoid arthritis (RA) undergoing MTX monotherapy. Methods Seventy-six patients with RA were included in this open prospective study: 40 were included before initiation of MTX therapy. Laboratory analyses, intracellular MTX concentrations in erythrocytes (Ery-MTX), and clinical examinations including toxicity data were performed prospectively for 52 weeks. Plasma concentrations of MTX were measured and area under the plasma concentration versus time curve (AUC) was estimated along with other pharmacokinetic variables in a population based software model. Results Ery-MTX rose after initiation of therapy and reached a steady state after 6–8 weeks. The correlation between steady-state Ery-MTX and dose was poor (r2 = 0.16), whereas steady-state Ery-MTX levels correlated strongly with the estimated AUC (r2 = 0.51, log-transformed variables). Both steady-state Ery-MTX levels and estimated AUC were significantly higher in patients responding to MTX therapy than in patients classified as nonresponders according to American College of Rheumatology core criteria and were similar to patients on longterm MTX therapy. Conclusion Our results indicate that clinical efficacy and Ery-MTX may have a causal relation and that measurement of Ery-MTX or estimation of AUC in a software model provides useful guidelines to the clinician when starting MTX therapy in patients with RA. The latter can be performed immediately after initiation of therapy.