Ревматоидный артрит (РА)-системное аутоиммунное ревматическое заболевание, характеризующееся хроническим воспалением синовиальной оболочки суставов и широким спектром внесуставных (системных) проявлений [1]. Создание регистров больных РА и другими воспалительными ревматическими заболеваниями (РЗ) относится к числу важнейших подходов к изучению клинических, научных и социальных проблем ревма-472 О р и г и н а л ь н ы е и с с л е д о в а н и я 1 ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой,

BackgroundTherapeutic control of the level of MTXPGs in erythrocytes may be an objective marker of its effective dose in RA treatment.ObjectivesTo evaluate the relationship between the level of MTXPGs in erythrocytes and the effectiveness of the dose of MT used by RA patients.MethodsThe 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.ResultsIt 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%.ConclusionFor 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

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BackgroundSafety of methotrexate (MT) therapy remains the most important issue of early rheumatoid arthritis (RA) therapy.ObjectivesA prospective evaluation of most common causes of MT discontinuation in RA patients with disease duration <3 years.MethodsAn open 1 year study included 106 patients with active RA meeting ACR/EULAR 2010 or ACR 1987 (DAS28 >3,2) criteria, naïve to subcutaneous (SC) MT. All pts were administered SC MT, starting with 10–15 mg/week dose, and following 5 mg up-titration each 1–2 weeks (to max 30 mg/week) until achieving the target (remission or minimum disease activity) or emergence of adverse reactions (AR). Pts’ monthly monitoring procedures included physical examination, blood analysis and biochemistry panel. T. Woodworth et al. inventory was used to assess the severity of ARs, and Naranjo scale was used to assess casual relationship of MT with an AR.ResultsTotally 12 (11%) MT discontinuations for the period of >3 weeks were analysed. Permanent discontinuation occured in 9 pts (8%), and temporary (from 4 weeks to 4 months)—in 3 (3%). 83% of all cases of withdrawal took place during the first 3 months. in 3 patients MT was discontinuated because of an AR and inefficiency. Combination of drug failure with AR was the reason for permanent SC MT discontinuation in 3 pts.The causes led to SC MT discontinuation were: skin reactions in 3 pts(25%), ”after-dose reactions”—in 2 (17%), allergic rash—in 2 (17%), diarrhoea—in 2 (17%), elevated liver enzymes—in 3 (25%), leukopenia – in 1 (8%), breast abscess—in 1 (8%). Some patients manifested multiple ARs. Two ARs (17%) were serious (grade 4 severity). Grade 3 ARs were documented in 4 cases (30%), Grade 2 ARs – in 4, and Grade 1 (mild) ARs – in 2 (17%) pts.Skin lesions became the underlying cause for SC MT discontinuation, such as active dermatitis (n=1) and lichenoid skin reaction (n=1).Totally 12 (11%) MT discontinuations for the period of >3 weeks were analysed. Permanent discontinuation occured in 9 pts (8%), and temporary (from 4 weeks to 4 months)—in 3 (3%). 83% of all cases of withdrawal took place during the first 3 months. in 3 patients MT was discontinuated because of an AR and inefficiency. Combination of drug failure with AR was the reason for permanent SC MT discontinuation in 3 pts. The causes led to SC MT discontinuation were: skin reactions in 3 pts(25%), ”after-dose reactions”—in 2 (17%), allergic rash—in 2 (17%), diarrhoea—in 2 (17%), elevated liver enzymes—in 3 (25%), leukopenia – in 1 (8%), breast abscess—in 1 (8%). Some patients manifested multiple ARs. Two ARs (17%) were serious (grade 4 severity). Grade 3 ARs were documented in 4 cases (30%), Grade 2 ARs – in 4, and Grade 1 (mild) ARs – in 2 (17%) pts. Skin lesions became the underlying cause for SC MT discontinuation, such as active dermatitis (n=1) and lichenoid skin reaction (n=1).ConclusionsSkin reactions were the most common cause for SC MT discontinuation. Therapeutic failure as the leading cause for drug discontinuation was not documented in a single patient.References[1...