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Patients with Rheumatoid Arthritis Treated with Methotrexate (MTX): Concentrations of Steady-state Erythrocyte MTX Correlate to Plasma Concentrations and Clinical Efficacy
NETE HORNUNG, TORKELL ELLINGSEN, JØRN ATTERMANN, KRISTIAN STENGAARD-PEDERSEN, and JØRGEN HJELM POULSEN
ABSTRACT. 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. (First Release July 15 2008; J Rheumatol 2008;35:1709-15) Key Indexing Terms:
RHEUMATOID ARTHRITIS
From the Department of Clinical Biochemistry and Department of Rheumatology, Aarhus University Hospital, and Department of Epidemiology, University of Aarhus, Aarhus, Denmark. N. Hornung, MD, PhD, Department of Quality and Research, Randers Regional Hospital, Randers; T. Ellingsen, MD, PhD, Department of Rheumatology, Aarhus University Hospital; J. Attermann, MS, PhD, Department of Epidemiology, University of Aarhus; K. Stengaard-Pedersen, MD, Dr Sci, Professor, Department of Rheumatology, Aarhus University Hospital; J.H. Poulsen, MD, Dr Sci, Department of Clinical Biochemistry, Hvidovre Hospital, Hvidovre, Denmark. Address reprint requests to Dr. N. Hornung, Department of Quality and Research, Randers Regional Hospital, Skovlyvej 1, 8900 Randers, Denmark. E-mail: neh@rc.aaa.dk Accepted for publication April 1, 2008. |
