Relationship between methotrexate dose and clinical efficacy for treatment of rheumatoid arthritis

Abstract

Objective To study the relation of methotrexate (MTX) dose with blood concentration of MTX polyglutamates (MTX-PGs) and clinical efficacy and explore the optimal initial dose of MTX for treatment of rheumatoid arthritis (RA). Methods We conducted a retrospective analysis of 165 RA patients receiving treatment in our hospital with MTX at the weekly oral dose of 10(n=67), 12.5(n=66) or 15 mg (n=32). The 28 joint disease activity scores (DAS28) were calculated before and after 8 weeks of MTX treatment. According to the European Union Anti-rheumatic Union (EULAR) criteria for efficacy evaluation, the clinical efficacy of the treatment was categorized into favorable responses (including significant and moderate responses) and nonresponse. High-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) assay was used to determine the blood concentration of MTX-PGs of the patients, and relations of MTX dose with the clinical efficacy, DAS28 after treatment and blood MTX-PGs concentration was analyzed. Results The patients taking MTX at the weekly dose of 10, 12.5 and 15 mg showed total response rates of 37.31%, 57.58%, and 56.25%, respectively, which was significantly lower in 10 mg group than in 12.5 mg group (P < 0.05). The median DAS28 after treatment was 3.92 (2.13-5.15), 2.80 (1.81-4.22), and 2.96 (2.26-3.67) in the 10, 12.5, and 15 mg groups, respectively, significantly higher in the 10 mg group than in 12.5 mg group (P < 0.05). The median blood concentrations of MTX-PGs in the 10, 12.5, and 15 mg groups were 92.0 (88.0-96.0), 112.0 (103.0-115.0), and 127.5 ng/mL (102.0-153.8 ng/mL), respectively, showing significant differences among the 3 dose groups (P < 0.05). An increased MTX dose was associated with a higher MTX-PGs concentration in these patients. In 10 mg group, the mean blood concentration of MTX-PGs was 92.5±7.0 ng/mL, significantly lower than the documented concentration (92.5±7.0 ng/mL) required to produce a clinical response (P < 0.05). Conclusion MTX at the weekly oral dose of 12.5 mg can be the optimal initial dose for treatment of local RA patients in Chongqing.

Keywords

• rheumatoid arthritis
• methotrexate
• polyglutamate methotrexates