A. Novikov

AB0370 Association of Clinical Efficacy with Serum Level of Adalimumab (ADA) and Anti- Adalimumab Antibody Levels in Patients with Early Rheumatoid Arthritis (RA)

Background ADA is effective and safe drug for the treatment of RA. Application of ADA can be accompanied by formation anti-adalimumab antibody (anti-ADA Ab) influencing on efficiency of therapy and the development of adverse events Objectives To evaluated the correlation of serum levels of ADA and anti-ADA Ab in relation to clinical response in patients (pts) with early RA Methods Serum levels of ADA (μg/ml) and anti-ADA Ab (positive/negative result) was determined by ELISA in 25 pts with early RA (15 women, mean age – 54,0; 47,0-58,0 years, mean disease duration - 8,0; 5,0-25,0 months, mean DAS 28 – 5,8; 4,9-7,5, SDAI 34,3; 22,8-54,2, CDAI 32,0; 21,7-48,4) baseline and then after 12 and 24 weeks of treatment. All patients received disease-modifying antirheumatic drugs (DMARDs) (100%>methotrexate) and ADA 40mg every 2 weeks. For all patients the ADA was the first biologic Results On the 12-th week of therapy values [Me; interquartile range] DAS 28 were 3,5 (3,2-4,4); SDAI-13,0 (7,0-16,6); CDAI - 10,8 (7,0-16, 0), 6 pts achieved a good EULAR response, 14- moderate response. On the 24-th week of treatment the value DAS 28 were 3,5 (3,1-4,4), SDAI-11,7 (7,4-17,5) and CDAI - 10,5 (6,2-16, 3), a good response was noted at 7 patients, moderate response - at 9 pts. The pts was distributed in two groups from serum levels of ADA: <3,0 (the first group n=7) and ≥3,0 (second group n=13). There were no differences between the groups on disease activity, level of acute-phase reactants by the 12th week of therapy (p>0,05). Higher disease activity and also the level of acute-phase reactants were marked out among pts of the first group (DAS 28 – 4,5; 3,3-4,9, ESR – 44; 18-57 mm/h, CRP -10,1; 4,9-34,5 mg/ml) compared with pts of the second group (3,5; 2,9-3,9, 15,0; 6,0-17,0 mm/h, 1,9; 0,75-6,7 mg/ml, respectively, p<0,05) by the 24th week of therapy. Also on the 24th week negative correlation was found with level of ADA and DAS 28 (r= -0,46; p=0,04), CRP (r= -0,54; p=0,02) and ESR (r= -0,5; p=0,02). Anti-ADA Ab was found in 3 (12,5%) pts at week 12 and in 2 (10%) pts at week 24. By 24th week of treatment at 100% of pts with presence of anti-ADA Ab was absence of clinical effect (ΔDAS28 = -1,36; -3,1-0,4). In the group of pts without anti-ADA Ab we found fewer of “no respondents” (11%) and identified positive dynamics DAS 28 (ΔDAS28=2,5; 1,66-2,9) (p<0,05) Conclusions Low drug level (<3,0 μg/ml) in serum is associated with a high clinical and laboratory disease activity at pts with early RA receiving the ADA therapy. By 12-24 weeks of ADA therapy anti-ADA Ab is found in 10-12,5% of pts, its formation is accompanied of decrease in efficacy of therapy Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2266

AB0395 Depression as a Risk Factor for Joints Destruction in Rheumatoid Arthritis Patients

Background Chronic depression is the most frequent psychiatric disorder in rheumatoid arthritis (RA) patients. Its considered that both depressive disorders and RA are stress-related and have a common proinflammatory pathogenesis. Moreover, depression decreases adherence to treatment and worsen the RA prognosis. That is why untreated depression may deteriorate the joints destruction in RA patients. Objectives To determine the factors associated with joints destruction in RA patients by linear regression analysis and the influence of chronic depression on joints destruction. Methods 125 RA patients were enrolled in this study. 86% were women with a mean age of 47.4±11.3 (M±m). The disease activity was assessed by DAS28 score. 52% of RA patients had a high activity of disease (DAS28>5,1). 67% of patients were taking prednisone in mean dose 5±2.7 mg/day (M±m). 80% were taking DMARDs: most of them - methotrexate (45%) and leflunomide (21%). All patients were taking NSADs. Psychiatric disorders was diagnosed by psychiatrist in accordance with the ICD-10 criteria in semi-structured interview. Psychiatric scales were used: Hospital Anxiety and Depression Scale, Hamilton Anxiety Rating Scale. Anxiety-depressive disorders were diagnosed in 93,6% of RA patients. Chronic depression - dysthymia and recurrent depressive disorder prevailed (32,8% and 25,6% accordingly). All patients were consulted by cardiologist. Dual-energy X-ray absorptiometry was used for osteoporosis detection. Results Most of RA patients (65,6%) had severe joints destruction - numerous bones erosions (III-IV X-ray stage of RA) or aseptic bones necrosis. The factors associated with severe joints destruction were found in Pearson correlation analysis. Then linear regression analysis was done and obtaining prognostic model showed that joints destruction was associated with RA (β=0,520) duration, chronic depression (dysthymia and recurrent depressive disorder) (β=0,235) and its duration (β=-0,124), osteoporosis (β=0,196) and ischemic heart disease (β=0,181), low body mass index (β=-0,108) and high RF-IgM level (β=0,121) (area under the ROC curve =0,930). Conclusions Chronic depression and its duration along with RA duration, osteoporosis and ischemic heart disease, low body mass index and high rheumatoid factor level are the leading factors of joints destruction in RA patients. Disclosure of Interest None declared

FRI0583 Comparison of Indirect Immunofluorescence (IIF) on HEP-2 Cells, Enzyme-Linked Immunosorbent Assay (ELISA) and Multiplex Bead-Based Immunoassay for Detection of Antinuclear Antibodies (ANA) in Systemic Lupus Erythematosus (SLE)

Background ANA are a diagnostic hallmark of SLE and others systemic autoimmune rheumatic diseases (SARD). Different methods have recently been developed for automated ANA detection, including IIF-HEp-2 interpretation systems, ELISA and multiplex immunoassay. Objectives The aim of the study was to compare the diagnostic performance of three automated methods for ANA detection (IIF-HEp-2, ELISA and BioPlex 2200) in SLE patients (pts). Methods We studied 94 pts (80 F, age 35.9[16.0;65.0] years, disease duration 113.5[2.0-576.0] months) with SLE (ACR criteria, 1997), 50 pts with others SARD, 20 pts with non-autoimmune RD and 30 healthy controls (HC). Serum samples were evaluated for the presence of ANA using automated IIF-HEp-2 system AKLIDES (“Medipan GmbH”, Germany), ELISA analyzer ALEGRIA (“Orgentec”, Germany) and automated multiplexed immunoassay system BioPlex 2200 ANA Screen (Laboratories Inc. Hercules, CA, USA). Positive results of ANA detection were corresponding to the following values: ≥1:160 (IIF-HEp-2), ≥1.3 U (ANA Screen, ELISA), ≥25.0 U (antigen-specific ANA, ELISA), ≥1.0 AI (antibody index) (BioPlex). Positive cutoff values for anti-dsDNA were ≥20.0 IU/ml (ELISA) and ≥10.0 IU/ml (BioPlex). Results The kappa agreement coefficients between IIF and ELISA, IIF and BioPlex were lower compared to ELISA and BioPlex (0.438,0.426, vs 0.726) for ANA screening. In SLE pts, ANA detection by IIF showed a higher diagnostic sensitivity than ELISA and BioPlex (0.97 vs 0.80, 0.83). The rate of false negative results was 3% for IIF, 20% for ELISA, 17% for BioPlex. The overall specificity (Sp) of the ANA screening test with IIF was lower than the Sp of ELISA and BioPlex (0.40 vs 0.70, 0.57). In HC group, the Sp of ANA detection was similar between IIF (0.93) and ELISA (0.97), while BioPlex ANA Screen had the lowest Sp (0.80). Negative test results by IIF had a lower likelihood ratio (LR) than ELISA and BioPlex (0.08 vs 0.29, 0.30), indicating that IIF was better to exclude SLE diagnosis. The agreement between ELISA/BioPlex testing for antibodies to dsDNA, Sm, RNP-70, Ro/SS-A (52/60 kD), La/SS-B was good (kappa=0.567, 0.673, 0.775, 0.816, 0.777, respectively). Both methods had a high diagnostic Sp for the detection of anti-dsDNA (0.94/0.95), anti-Sm (0.97/0.97) and anti-RNP (0.94/0.95) in SLE. Positive LR of anti-dsDNA and anti-Sm antibodies testing by ELISA/BioPlex (11.50/10.42 and 7.10/9.57) demonstrated the most useful values for SLE diagnosis. Conclusions ANA detection using automated IIF-HEp-2 interpretation systems is a most useful screening test in SLE. Solid-phase immunoassay methods (ELISA and BioPlex 2200) should be used as confirmatory tests to detect antigen-specific ANA. Disclosure of Interest None declared

AB0393 Comparison of multi-line dot assay and enzyme-linked immunosorbent assay for detection of autoantibody profile in antiphospholipid syndrome

Background Diagnosis of antiphospholipid syndrome (APS) still remains a laboratory challenge due to the great diversity of antiphospholipid antibodies (aPL) and their significance regarding APS classification criteria. Standardized enzyme-linked immunosorbent assay (ELISA) for antibodies to cardiolipin (aCL) and b2-glycoprotein I (ab2GPI) has been indispensable in the diagnosis and management of APS. Multiplex detection of aPL profile seems to be a new approach for risk assessment in APS. Objectives The comparison of the novel multi-line dot assay (MLDA) with results of the routine ELISA technique for detection of aPL in APS. Methods We studied 36 patients (pts) with APS (5 men, 31 women, median age 34, 29-44 years). Diagnosis of APS had been established according to the 2006 international classification criteria. 15 (41,7%) APS pts met the diagnostic criteria for systemic lupus erythematosus (SLE), 28 (77,8%) had a history of arterial and/or venous thrombosis, 21 (58,3%) suffered from fetal loss. As a disease control group, 14 pts with SLE without APS (3 men, 11 women, median age 35, 27-45 years) were included. IgG/IgM antibodies to CL, b2GPI, phosphatidylserine (aPS) and phosphatidylinositol (aPI) in the pts sera were detected using a commercial available MLDA (“Medipan”, Germany). For comparison, the serum levels of IgG/IgM aCL and ab2GPI were measured by ELISA kit (“Orgentec”, Germany). Results APS pts demonstrated a significantly higher frequency of IgG aCL, IgG and IgM ab2GPI in ELISA and IgG aCL in MLDA compared to SLE pts (p<0,05) (table 1). The agreement between both methods was good for IgG aCL, IgM aCL and fair for IgG ab2GPI, IgM ab2GPI (kappa=0,620, 0,628, 0,380 and 0,388, respectively). The frequency of discrepant results for IgG aCL, IgM aCL, IgG/ IgM ab2GPI was 16%, 18% and 30%. Multiple positivity for different aPL detected by ELISA occurred significantly more frequently in APS pts (27,8%) in contrast to SLE pts (7,1%, p<0,05). The number of multiple positive samples evaluated by MLDA in the APS group (13,9%) did not demonstrated a significant higher prevalence in comparison with the control group (7,1%, p>0,05). There was a relationship between ischemic stroke and the combination of high positive levels of IgG/IgM aCL, ab2GPI, aPS and aPI detected by MLDA in APS pts (OR 95%CI 2,45, 1,09-5,55, ρ=0,049). We didn’t find any associations between subtypes of aPL and thrombosis localization. Image/graph Conclusions MDLA present an alternative to ELISA for aPL evaluation and profiling in APS. The rate of false-positive aPL detected by MLDA in SLE pts was higher compared to ELISA. The combination of four high positive aPL measured by MLDA is a risk factor of ischemic stroke in APS. Disclosure of Interest None Declared

FRI0241 The effect of abatacept on cytokine profile in patients with rheumatoid arthritis

Background Pathological activation of T-cells with the overproduction of pro-inflammatory cytokines is playing a major role in the pathogenesis of rheumathoid arthritis (RA). The influence of the selective co-stimulation modulator abatacept (ABA) on the dynamics of cytokine profile in patients with RA is not fully understood. Objectives To assess the changes in cytokine profile in patients treated with ABA. Methods 44 patients with RA and an inadequate response to synthetic DMARDs or biologics were enrolled in the study. Most of them were middle aged females (46,9±13,9 years) with median RA duration 2 years (1,4–3), high disease activity (DAS28=5,2±0,8), RF-positive (80%) and ACPA-positive (79,5%). 16 healthy individuals were included in the study as control. The serum levels of IL-1, IL-6, IL-17, TNF-α, VEGF, IP-10 (pg/ml) were measured by ELISA immunoassay, YKL-40 by MicroVue immunoassay at baseline and 24 weeks. Disease activity was measured by DAS28, results were assessed every 12 weeks by EULAR criteria. ABA was administered intravenously every 4 weeks. Results Levels of IL-6 (2.4 (1,1–6,4) vs 0.7 (0,62–1,0), p=0,0002), YKL-40 (97 (68,4–97, 9) vs. 64 (52,4–107,5), p=0,03), IP-10 (21 (12,9–49,8) vs 14 (9,2–15,2), p=0,005) were significantly higher in patients with RA compared to control. ABA significant reduced disease activity already after 12 weeks of therapy (p<0,05). After 24 weeks of ABA therapy good and moderate response by EULAR criteria was achieved in 86%, low disease activity by DAS28 in 52%. By the 6-th month ABA significant decreased levels of IL-6 (1,29 (0,9–2,2, p=0,0006), IP-10 (14 (7,5–28), p=0.007) as well as MMP3: before 30.1 (13–82), after 24 weeks 10 (7.4–55), p=0.0003 and RF: before 218 (9.6–187), after 24 weeks 159 (9.7–155), p=0.02. Lowering of the IL-6 (r=0,5) and IP-10 (r=0,32) levels were significantly (p<0.05) associated with a decrease of DAS28. Conclusions ABA therapy leads to a significant reduction in serum levels of IL-6, IP-10, MMP3 and RF. The serum levels of IL-6 and IP-10 correlate with decrease activity of RA. Disclosure of Interest None declared

AB0230 Polymorphism of cytotoxic T-lymphocyte 4 +49A/G is associated with early prescribing the biological therapy in active early rheumatoid arthritis patients (ERA PTS) refractory to the previous subcutaneous methotrexate (SC MTX) monotherapy

Background Monotherapy with MTX is the first step of RA therapy as recommended by EULAR. According to “Treat to Target” (T2T) strategy principles insufficient response to MTX requires prompt switch to a combination therapy with biological agents. Objectives To find out whether polymorphisms of immune response genes are associated with early prescribing the biological treatment in eRA pts, refractory to the SC MTX monotherapy. Methods By January 2014, 210 pts with RA were included in the REMARCA study (Russian InvEstigation of MethotrexAte and biologics in eaRly aCtive inflammatory Arthritis), and 88 pts have passed the 12 months control point. All pts started SC MTX monotherapy with rapid up-titration of the dose from 10 to 25–30 mg/week. Therapy was revised every 3 months using DAS28, SDAI and CDAI indices. Combination with biologics (in most cases TNF inhibitors) was used in 57 (65%) of pts at (median) 3 [3;6] month [1]. Retrospectively, 45 out of 88 active eRA pts (35 woman, mean age 53,5; 46–59,5 years, mean disease duration 7,0; 4,0–11,5 months, mean DAS28 5,8; 4,9–6,4, mean hs-CRP 27,0; 9,7–61,0 mg/l) were selected to evaluate the changes in cytokine profile in MTX-naive pts during SC MTX and SC MTX + adalimumab (SC MTX+ADA) therapy [2]. These 45 pts were genotyped for the following gene polymorphisms (SNPs): PTPN22 (+1858 C/T, rs2476601), CTLA4 (+49A/G, rs231775), TNFAIP3 (rs675520, rs6920220, rs10499194), IL6 (-174G/C, rs1800795), IL6R (+358A/C, rs8192284), TNFA (-308A/G, rs1800629), MCP1/ CCL2 (+2581A/G, rs1024611), IL10 (-592A/C, rs1800872, -1082 A/G, rs1800896), IL1A (-889C/T, rs1800587), IL1B (+3953C/T, rs1143634). Results By the end of 3 months of SC MTX therapy, 23 out of 45 eRA pts (51,1%) adequately responded to SC MTX (EULAR criteria) and continued on SC MTX monotherapy. In 22 pts (48,9%) SC MTX monotherapy failed, thus they were switched to SC MTX + ADA combination therapy. CTLA-4 gene polymorphism (+49A/G) was the only predictor for the administration of biological therapy in eRA pts, that was confirmed by a logistic regression analysis [OR=7,7 95% CI 1,4–40,9, p=0,017]. The carriers of at least one G allele (AG/GG genotypes) received the biological therapy more often than subjects with AA genotype (20/22, 90,9% and 13/23, 56,5% respectively). Moreover, the CTLA-4 (+49A/G) genotypes (AG/GG vs AA respectively) were associated with DAS28 (3,6±1,1 and 4,6±1,6, p=0,04), the number of tender joints (3,1±3,1 and 7,1±5,1, p=0,016), the number of swollen joints (2,7±2,5 and 5,3±4,9 p=0,024), SDAI (11,1±7,2 and 20,2±12,1, p=0,018), CDAI (10,6±7,1 and 18,6±10,6, p=0,025) and CRP (6,3±12,1 and 21,8±37,1 p=0,018) values after 3 months of SC MTX monotherapy. Conclusions Our data suggest that CTLA-4 (+49A/G) genetic polymorphism is associated with more severe rheumatoid arthritis and may predict the need for early administration of biological therapy. References Karateev D., E. Luchikhina E., N. Demidova N. et al. Ann Rheum Dis 2014;73(Suppl2): 235–236. Avdeeva A.S. Novikov A. A, Aleksandrova E. N. et al. Ann Rheum Dis 2014;73(Suppl2): 215–216. Disclosure of Interest None declared

SAT0113 Implementation of The Treat-To-Target Strategy Leads To Dramatically Reduction of N-Terminal Pro-Brain Natriuretic Peptide Level in Patients with Early Rheumatoid Arthritis: Table 1.

Objectives to study the effect of antirheumatic therapy administered in accordance with “treat-to-target” principles on NT-proBNP level in early rheumatoid arthritis (RA) patients (pts) during 18-month follow-up Methods A total of 66 early RA pts (ACR/EULAR criteria, 2010) were included in the study: 71% of women, age 56 [46;61] years, disease duration 6 [4;8] months; DAS28 5.3 [5.0;6.2], positive for ACCP (100%), RF (87%), without prior administration of DMARDs and glucocorticoides. The control group consisted of 27 healthy subjects, which were matched by sex and age. Methotrexate (MT) therapy was started in all pts with an escalation of the dose up to 30 mg/week subcutaneously. Incase of no remission 3 months (mon) later, MT was added with biologic therapy (BT): Adalimumab, Certolizumab pegol, Abatacept. After 18 mon 27 (41%) pts achieved remission. Antihypertensive therapy was administered in 51 (77%) pts: ACE inhibitors, ARBs, beta-blockers, calcium antagonists, diuretics. The normal range for NT-proBNP was less than 125 pg/ml. Results At baseline the concentration of NT-proBNP in early RA pts (125 [65;208] pg/ml) was higher than in control group (52 [40;69] pg/ml), p<0,05. In 32 (49%) RA pts NT-proBNP level were higher than normal. Pts with elevated NT-proBNP level compared to pts with normal one were older (60 [56;65] vs 50 [35;55] years), have a higher frequency of carotid atherosclerosis (85% vs 43%), coronary artery calcinosis (69% vs 22%), chronic heart failure (CHF) (20% vs 0%), ischemic heart disease (28% vs 5%), as well as a higher BMI (28 [24;31] vs 24 [22;29] kg/m2), CRP (34 [13;78] vs 14 [3;41] mg/l), p<0,05 for all cases. The frequency of dyslipidemia, abdominal obesity, diabetes mellitus were not obtained between the groups. After 18 mon NT-proBNP level decreased from 125 [65;208] to 68 [33;115] pg/ml, p<0,05. There were also reduction in the number of pts with high NT-proBNP level from 49% to 21%, p<0,05. Pts who achieved remission showed a decrease in the number of pts with high NT-proBNP level (from 41% to 7%), p<0,05, and those who disease activity remained showed a decrease in the number of pts with high NT-proBNP level (from 54% to 31%), p<0,05. In group of MT+BT revealed a more pronounced decrease in NT-proBNP level (from 50% to 15%), p<0,05, than in group MT (46% vs 31%), p>0,05. The most pronounced decrease NT-proBNP level was in pts who achieved remission on MT+BT therapy (Tabl.1). There were correlation between ΔNT-proBNP and ΔCRP (r=0,4;p<0,05).Table 1. The elevated NT-proBNP level depending on achieved RA activity and therapy DAS28<2,6 (n=27) DAS≥2,6 (n=39) MT (n=15) MT+BP (n=12) MT (n=11) MT+BP (n=28) 0 mon 18 mon 0 mon 18mon 0 mon 18 mon 0 mon 18 mon NT-proBNP, n (%) 5 (33%) 2 (13%) 6 (50%) 0 (0%) 7 (64%) 6 (55%) 14 (50%) 6 (21%) Conclusions At baseline NT-proBNP concentration in early RA pts were higher than in control group and its level correlated with age, traditional risk factors of cardiovascular disease (CVD), CVD, disease activity, markers of inflammation. Achieved remission especially in case of MT+BP therapy leads to a more pronounced reduction in NT-proBNP level. That can contribute to reduce the risk of CHF. Disclosure of Interest None declared

THU0284 Dynamics of B Lymphocyte Subsets in SLE Patients Treated with Rituximab

Objectives to study B-cell subsets dynamics in SLE patients receiving rituximab (RTX) therapy with following 6 months observation. Methods The study included 16 SLE pts (1m/15f) with high (SLEDAI2K>10 - 13 pts.) and moderate (SLEDAI2K<10- 3 pts.) disease activity. Out of them 7 pts with lupus nephritis and 3 pts with neurolupus. RTX was administered to pts who failed to respond to glucocorticoids (GCs) and cytostatics (CTs). B-cells subsets were assessed before RTX administration (month 0), and at month 3 and month 6 of RTX therapy. RTX was administered at 500 to 2000 mg doses depending on disease activity. We investigated the absolute and relative number of CD19+ B cells, the total population of memory B cells (CD19+CD27+), “preswitch” (CD19+IgD+CD27+) and “postswitch” (CD19+IgD-CD27+) memory B cells, naive (CD19+IgD+CD27-) and transitional (CD19+IgD+CD10+CD38++CD27-) B cells, plasmablasts (CD19+CD38+++IgD-CD27+CD20-), short-lived plasma cells (CD19+CD38+), long-lived plasma cells (CD19+CD138+), and double-negative B-cells (CD19+CD27-IgD) were measured. All B cell subsets were analyzed by technique of multicolor flow cytofluorometry using panel of monoclonal antibodies to surface membrane markers of B-lymphocytes. Results Following initiation of RTX SLE clinical and lab activity indices have decreased in all 16 pts by month 3 and month 6 of follow up (SLEDAI-2K 0 month –Me 15 [11;19], 3 month -Me 7 [3;10], 6 month –Me 5 [4;9], p<0.05), as well as decrease of absolute count CD19 B-cell subpopulation (0 month – Me 0,11 [0,0741; 0,2], 3 month - Me 0,0017 [0; 0,003], 6 month - Me 0,0045 [0,0005; 0,01], p<0.05). B-cell repopulation by 6 month in 11 out of 16 pts was due to “naive” B-cells Me 0,00085 [0; 0,008], double negative Me 0,001 [0; 0,0025] and “postswitch” memory B-cells Me 0,0013 [0,0001; 0,003]. SLE exacerbation by 6 month was documented in 5 pts, in 3 out of them B-cell repopulation occurred. A correlation between baseline high SLE activity before RTX infusions (SLEDAI-2K 5 pts – Me 20 [18;24], 11 pts. Me 12 [8;12]) and SLE exacerbation at 6 month after initiation of RTM therapy (p<0,05, r=0,54) was found. Conclusions Decrease in clinical and lab SLE activity was documented in all 16 pts by 3 month after one course of RTM therapy. In 3 out of 5 exacerbated pts at 6 month B-cell repopulation was found, but without significant correlation with counts of B-cells subpopulations during the whole follow up period. Disclosure of Interest None declared

THU0171 Effect of Fast Escalation of The Dose of Subcutaneous Methotrexate on The Need for Biological Dmards in Patients with Very Early and Established Rheumatoid Arthritis: Table 1

Background The ongoing REMARCA study (Russian acronym: Russian InvEstigation of MethotrexAte and biologics in eaRly aCtive inflammatory Arthritis) included patients with early and established active RA, who did not use subcutaneous methotrexate (SC MTX) and/or biologics. The main goal of the study is an adaptation of “Treat to target” (T2T) recommendations for clinical practice. Objectives The purpose of this part of REMARCA trial is to compare two regimens of escalation of the dose of SC MTX in pts with very early (duration of symptoms ≤6 months) and established RA. Methods 191 patients (pts) with active severe RA (34 males, 157 females, 51,8% with very early RA, 80,1% RF(+), 81,2% anti-CCP(+), DAS28 5,52±1,12, SDAI 30,8±14,7, CDAI 27,3±12,5) were followed up for at least 12 months, among them 115 pts (18 males, 97 females, 60% with very early RA) were followed for 24 months. All patients received SC MTX as a fist-line therapy. We used two regimens of SC MTX dose escalation: 1) fast escalation – starting dose 15 mg/week increasing with increments of 5 mg every 1–2 week to achieve 20–30 mg/week in 4–6 weeks; 2) “slow” escalation (usual recommendations) - starting dose 10 mg/week increasing with increments of 2,5–5 mg every 2–4 week to achieve maximal dose in 8–12 weeks. Fast and “Slow” regimens were prescribed in random manner (with exception of pts who had signs of probable safety problems, such as liver, kidney disease etc., when “slow” regimen used). Use of oral steroids was limited to continuation of previously administered low doses (in 14,7% pts) and intra-articular injections (2 doses per 3 months). Therapy revision and initiation of biological DMARDs in combination with SC MTX (adalimumab, certolizumab, or abatacept), was made every 3 months (or more often if indicated) in order to reach T2T targets. Results After 12 months, 73 (38,2%) pts achieved SDAI low disease activity (LDA) and 65 (34%) achieved SDAI remission. In the group followed up to 24 months, 45 (39%) and 49 (42,6%) achieved stable SDAI LDA or remission respectively. At 12 month 36,1% pts responded well to monotherapy with SC MTX, and 63,9% required a switch to a combination therapy with biologics. In the group followed up to 24 months the proportion of pts left on MTX monotherapy and switched to biologics was 32,2% and 67,8% resp. Fast escalation regimen used in 87 (45,5%) pts was associated with less need for biologic therapy (see table). When fast escalation used in pts with very early RA (n=47, 24,5%), monotherapy with SC MTX was sufficient in 68,1–66,7% of pts.Table 1 12-month follow-up, n=191 24-month follow-up, n=115 SC MTX monotherapy (n=69) SC MTX + biologics (n=122) SC MTX monotherapy (n=37) SC MTX + biologics (n=78) Fast vs “Slow” escalation of SC MT 49.4% vs 25%* 50.6% vs 75%* 46.3% vs 19.7%* 53.7% vs 80.3%* Fast escalation of SC MT + very early RA vs All other pts 68.1% vs 25.7%* 31.9% vs 74.3%* 66.7% vs 19%* 33.3% vs 81%* *p<0,01 between groups. Conclusions Early administration of SC MTX with fast escalation of the dose leads to the achievement of T2T goals without need for combination with biological DMARDs in 2/3 of patients with severe active RA. Acknowledgement Trial State registration number: 01201454666 (http://www.rosrid.ru/search) Disclosure of Interest None declared

AB0030 Cytokine Profiles in Systemic Lupus Erythematosus and Rheumatoid Arthritis

Background Our aim was to compare serum levels of cytokines in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Objectives Comparative data on cytokine profile in SLE and rheumatoid arthritis RA patients are scarce. Methods We examined serum samples from 80 pts with SLE, median and interquartile range (25th–75th percentile) of disease duration 48 (2–432) months; age 31,5 (16–65) years; 72 female; 74 pts with RA, disease duration 90,0 (30,00–192,0) months; age 54,0 (44,0–62,0) years; 59 female, and 28 healthy donors. Cytokine analyses were performed with Bio-Plex® technology (Human Grp I Cytokine 27-plex panel). Results Pts with SLE had significantly lower levels of IL-1β, -1ra, -2, -9, eotaxin, G-CSF, IFN-γ, MIP-1β, TNF-α, VEGF and higher levels of IL-4, -6, -8, -12, GM-CSF, MCP-1, PDGF-BB, RANTES than healthy donors. Compared to RA, cytokine/chemokine levels from SLE were significantly different. The concentrations of IL-1β, -1ra, -2, -5, -6, -7, -9, -10, -13, 15, eotaxin, FGF, G-CSF, IFN-γ, IP-10, MIP-1α, TNF-α, VEGF in SLE were significantly lower than RA. The concentrations of IL-4, -8, MCP-1, MIP-1β, PDGF-BB, RANTES was higher in the SLE cohort (Table 1). Conclusions Serum concentration of most proinflammatory, Th-2 related, bone marrow–derived cytokines, stromal cells and angiogenic factors in SLE pts is substantially lower than in healthy donors and pts witch RA. These data demonstrate significantly higher chemokine levels in SLE versus RA. References Chun HY, Chung JW, Kim HA, Yun JM, Jeon JY, Ye YM, Kim SH, Park HS, Suh CH. Cytokine IL-6 and IL-10 as biomarkers in systemic lupus erythematosus. J Clin Immunol. 2007; 27(5):461–6. Kokkonen H, Söderström I, Rocklöv J, Hallmans G, Lejon K, Rantapää Dahlqvist S. Up-regulation of cytokines and chemokines predates the onset of rheumatoid arthritis. Arthritis Rheum. 2010; 62(2):383–91. doi: 10.1002/art.27186. Sieber J, Daridon C, Fleischer SJ, Fleischer V, Hiepe F, Alexander T, Heine G, Burmester GR, Fillatreau S, Dörner T. Active systemic lupus erythematosus is associated with a reduced cytokine production by B cells in response to TLR9 stimulation. Arthritis Res Ther. 2014;16(6):477. doi: 10.1186/s13075-014-0477-1. Disclosure of Interest None declared