Preliminary study to identify the predictive factors for the response to methotrexate therapy in patients with rheumatoid arthritis

Sachie Inoue, Masayuki Hashiguchi, Kenji Takagi, Shinichi Kawai, Mayumi Mochizuki

研究成果: Article査読

19 被引用数 (Scopus)

抄録

To identify the major factors predicting the response to Methotrexate (MTX) therapy in rheumatoid arthritis (RA) patients, we evaluated the relationship between the response to MTX and factors such as the concentration of MTX-polyglutamates (MTX-PGs) in erythrocytes (RBCs), genotypes of thymidylate synthase (TYMS) 5′-UTR (2R/3R) and 3′-UTR (-6/+6), 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and other patient-related factors. Thirty-six Japanese RA patients were enrolled in this cohort study. The concentrations of MTX-PGs in RBCs were measured, and polymorphisms were determined using PCR-RFLP method. As an indicator of the accumulated capacity of MTX-PGs in the RBCs of each patient, the MTX dose/MTX-PGs (AC-MPG, l/week) was calculated. The response to MTX therapy was assessed using the MTX dose for a ≥50% decrease in CRP level (MTX dose for 50% CRP, mg/week), and the relationships between MTX dose for 50% CRP and various other factors were evaluated using multiple linear regression analysis. The MTX dose was 6.9±0.3 mg/week and the MTX-PGs concentration in RBCs was 97.3±8.1 nmol/l (n=36, blood samples=95, mean±S.D.). The range of MTX dose for 50% CRP was 2.0-13.0 mg/ week. Most individual AC-MPG levels showed no change during the evaluation period (coefficient of variation=5.9%). Based on the results of multiple linear regression analysis, AC-MPG, TYMS 3′-UTR (-6/+6), and ESR at the start of MTX therapy were associated with the MTX dose for 50%CRP. AC-MPG, TYMS 3′-UTR (-6/+6), and ESR might be the major predictive factors for the response to MTX therapy in Japanese RA patients.

本文言語English
ページ(範囲)843-849
ページ数7
ジャーナルYakugaku Zasshi
129
7
DOI
出版ステータスPublished - 2009 7

ASJC Scopus subject areas

  • 薬理学
  • 薬科学

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