FRI0151 THE RELATIONSHIP BETWEEN THE EFFECTIVENESS OF METHOTREXATE (MTX) IN RHEUMATOID ARTHRITIS (RA) AND MTX POLYGLUTAMATES LEVELS (MTXPGS) IN RED BLOOD CELLS BY TANDEM CHROMATOMASS SPECTROMETRY (PILOT STUDY). (June 2019) - Gridneva, Galina
Abstract : Background: Therapeutic control of the level of MTXPGs in erythrocytes may be an objective marker of its effective dose in RA treatment. Objectives: To evaluate the relationship between the level of MTXPGs in erythrocytes and the effectiveness of the dose of MT used by RA patients. Methods: The study included 60 random selected RA patients over the age of 18, 16 men and 44 women. The diagnosis in all cases met the criteria of ACR/EULAR 2010. All pts received MTX at a constant dose of at least 20 mg per week subcutaneously for at least the last 12 weeks. Patients were divided into 2 groups depending on the presence (group 1, n = 30) or absence (group 2, n = 30) of the therapeutic effect of MTX, according to the criteria of the EULAR response to therapy. The groups were comparable in age, sex, alcohol intake, smoking, body mass index (BMI), ACPP-positivity, incidence of unwanted reactions to MTX, single dose of MTX, duration of MTX treatment course. The groups differed in duration of the disease at the beginning of the current course of continuous therapy: 5.5 [2.0, 12.0] months in group 1 and 12.0 [3.0, 60.0] months in group 2; in group 2 patients received glucocorticoids (GK) orally 17 (57%) against 9 (30%) in group 1. Blood sampling was performed no later than 36 hours after the last administration of methotrexate. From each patient 2 ml of hemolysed blood were examined using an Agilent 6410 chromatograph (Agilent Technologies) - a quantitative measurement of methotrexate polyglutamate by liquid chromatography-spectrometry. Results: It was established that the levels of total MTXPG and MTXPG1, 2, 3, 5 in erythrocytes did not depend on the effectiveness of MTX, the dose of which was comparable in all patients. At the same time, the level of MTXPG4 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). Evaluation of the ROC curve showed that MTXPG4 values below 22.5 nmol/l corresponded to the absence of the therapeutic effect of MTX. The area under the curve was 0.672, (CI 95 0.536-0.808); p = 0.022. Sensitivity - 77%, specificity - 53.3%. Conclusion: For effective treatment of RA patients, it is necessary to administer such doses of MTX so that the achieved level of MTXPG4 in erythrocytes is not less than 22.5 nmol/l. Disclosure of Interests: Galina Gridneva: None declared, Yury Muraviev: None declared, Alexander Lila Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc., Natalia Baymeeva: None declared