Abstract

Study of the ratio of the concentrations of methotrexate (MTX) metabolites in the red blood cells of patients with rheumatoid arthritis (RA)-

Author(s): Galina Gridneva

Statement of the Problem: The concentration of MTÐ¥ polyglutamates (MTÐ¥PG) in red blood cells may become an objective therapy response predictor. Objective is to study the correlation between the level of MTÐ¥PG in patients taking methotrexate in stable doses, on the therapeutic response.

Methodology & Theoretical Orientation: The study included 60 (44 women and 16 men) adult (>18 years old) RA patients according to ACR/EULAR 2010 criteria. Group 1 (n=30) had good therapeutic effect on MTX therapy according to the EULAR criteria of the treatment effectiveness. Group 2 (n = 30) had moderate or no effect. MTXPG (total and MTXPG 1,2,3,4,5) were determined in erythrocytes by tandem mass spectrometry. The therapy was: MTX subcutaneously at least 20 mg/week, for 12-225 weeks before including.

Results: The weekly dose of MTX was comparable in all patients. It was established that the levels of total MTPG and MTPG1,2,3,5 in erythrocytes did not correlate with the effectiveness of MTX. At the same time, the level of MTPXG4 was significantly higher (p = 0.023) in patients of group 1 (26.4±6.1 nmol/l) compared with patients in group 2 (22.1±6.8 nmol/l). ROC-analyses showed that MTPG4 values below 22.5 nmol/l matched to the absence of the therapeutic effect of MT. The area under the curve was 0.672, (CI 95 0.536- 0.808); p=0.022. Specificity-53.3%, sensitivity - 77%.

Conclusion: The target level of MTXPG4 in erythrocytes to achieve a good therapeutic response is 22.5 nmol / L or more.