| Popis: |
Background Methotrexate (MTX) is an anchor drug in the treatment of rheumatoid arthritis (RA). We previously performed a cross-sectional, observational study and reported an association between the gene expression level of the drug transporter ABCG2/BCRP (breast cancer resistance protein) and RA disease control in patients receiving MTX. Methods We designed a prospective study in two medical centers in Japan to confirm the association of ABCG2 gene expression level with the clinical response to MTX in MTX-naive patients with RA. The primary endpoint of this study was good response based on the European League Against Rheumatism (EULAR) response criteria by Disease Activity Score using 28-joint count (DAS28). We evaluated the association between the baseline expression of six genes involved in the intracellular pharmacokinetics of MTX, including ABCG2, as well as their temporal changes, and the clinical response at week 12 from the initiation of MTX. Results Based on the clinical response at 12 weeks after the initiation of MTX, a total of 24 patients were classified into the good responders (n = 9) and non-good responders (n = 15; 10 moderate responders and 5 non-responders) groups. A univariate logistic regression analysis of baseline gene expression levels for the prediction of the EULAR good response at week 12 showed a significant association with ABCG2 alone, and the rate of baseline expression of ABCG2 mRNA above the cut-off value determined by a receiver operating characteristic curve was higher in good responders than in non-good responders (p = 0.012). Moreover, ABCG2 expression decreased in almost all good responders, but not in non-good responders, after MTX treatment for 12 weeks (median -76% versus +41% from baseline, respectively; p = 0.011). The ABCG2 gene expression level did not correlate with DAS28 at baseline or at week 12, and neither did the rate of change in ABCG2 gene expression level. Conclusions We have confirmed the association between the gene expression level of the drug transporter ABCG2 and the clinical response to MTX in patients with RA. |
