Background According to Treat to Target (T2T) recommendations the primary goal of treatment of patients (pts) with rheumatoid arthritis (RA) is clinical remission. This implies a revision of treatment every 3-6 months with the use of combination therapy if necessary. Assessment of the results of applying the T2T strategy into practice is an important task. Objectives To study the results of treatment according the T2T strategy in pts with RA in clinical practice. Methods The REMARCA (Russian investigation of MethotrexAte and biologics in eaRly aCtive inflammatory Arthritis) investigator-initiated trial includes pts with asevere ctive RA. All pts started treatment with SC MTX monotherapy using fast increase from 10 to 25-30 mg/week. To exclude the influence of steroids, we allowed only 2 intra-articular injections per every 3 months (pts could continue steroids per os in low doses if prescribed before the enrollment in the study). Therapy was revised every 3 months using DAS28, SDAI and CDAI indices. The goal of treatment was clinical remission or low disease activity (LDA) as quickly as possible. Results By January 2014, 210 pts with RA were included, and 88 pts have passed the 12 months control point (22 males, 66 females, 92% IgM RF positive, 87,5% anti-CCP positive, including 46 pts with early RA (duration≤6 months) and 42 pts with long-standing RA (duration 22 [11;53] months). At 6 months we achieved LDA or remission according to DAS28 in 43 (49%), SDAI in 53 (60%), CDAI in 55 (63%) of pts. At 12 months LDA or remission were observed by DAS28 in 54 (61%) of pts, SDAI – 65 (74%), CDAI in 67 (76%) of pts. Combination with biologics (in most cases TNF inhibitors) was used in 57 (65%) of pts at (median) 3 [3;6] month. There were 13 cases of switching between biologics. Remission was observed more often during the first 6 months among patients who did not require biological therapy, but at 12 month combination therapy group showed similar results (table 1). “Functional remission” (HAQ≤0,5) was observed significantly more frequently in patients with good initial response to SC MTX. Patients with early RA significantly less likely required treatment with biologics (52%) than patients with long-standing RA (79%, p=0,014). Table 1. Remission rates at 6 and 12 months of treatment Patients characteristic MTX monotherapy, MTX + biologics, p n=31* n=57* (chi-square) DAS28 remission at 6 months, n=21 12 (39%) 9 (16%) 0,001 DAS28 remission at 12 months, n=41 15 (48%) 26 (46%) 0,26 SDAI remission at 6 months, n=17 10 (32%) 7 (12%) <0,001 SDAI remission at 12 months, n=34 15 (48%) 19 (33%) 0,31 CDAI remission at 6 months, n=17 11 (35%) 6 (11%) <0,001 CDAI remission at 12 months, n=32 14 (45%) 18 (32%) 0,27 HAQ ≤0,5 at 6 months, n=39 20 (65%) 19 (33%) 0,015 HAQ ≤0,5 at 12 months, n=46 21 (68%) 25 (44%) 0,017 *Percentage in column. Conclusions SC MTX monotherapy allowed to achieve LDA or remission in the vast majority of patients with good response to treatment. In patients who did not...

Objectives To compare safety data in patients (pts) with early (<2 years duration) RA who were randomly assigned to receive 4 different regimens of DMARDs treatment. Methods One hundred forty-one pts with RA of less than 2 years duration (122 women, mean age 51 years, mean disease duration 24 weeks, mean DAS 28 5,9; 64% RF-positive,59% ACCP-positive) were randomly allocated to receive one of the following treatment regimens: methotrexate (MTX, up to 20 mg/week, 35 pts); MTX plus prednisolone (P) 10 mg daily (MTX-P, 34 pts); MTX-P plus methylprednisolone (MP) 1000 mg intravenously on the first day of treatment (MTX-P-MP, 35 pts); leflunomide 20 mg daily (LEF, 37 pts). Duration of treatment was one year. Control points were 3, 6 and 12 months from the initiation of therapy. Safety data was assessed at the main control points. Results At baseline all groups were comparable in their demographic, clinical and radiographic characteristics. One hundred twenty-seven pts completed the study. Side effects were registered in the same number of patients in each group (9 patients; 24,3%>26%). Therapy had to be stopped in six patients due to side effects: MTX - 1(depigmentation of the skin), MTX-P - none, MTX-P-MP - 1 (stomatitis) and LEF - 4 (dermatitis-2; pancytopenia with platelet count 43 ×109/L, erythrocyte 2,9×1012/L, WBC 2×109/L-1; angioedema, periorbital edema and dermatitis with itching-1). Other side effects were mild: MTX - 8 pts (dyspepsia-1, elevation of transaminases-6, hair loss-1), MTX-P - 9 pts (Cushing’s syndrome - 1, hair loss - 1, anemia - 1, elevation of transaminases - 4, arterial hypertension - 2), MTX-P-MP - 8 pts (hair loss-1,dermatitis-1, elevation of transaminases-5, Cushing’s syndrome - 1) and LEF - 5 pts (elevation of transaminases-5). Conclusions Safety profile was the same in all groups. In most cases side effects were moderate or minimal. The most serious side effects, leading to the discontinuation of the therapy, were registered in LEF group. There was no withdrawal of treatment in MTX-P group. Disclosure of Interest None Declared

BackgroundMethotrexate (MT) – is one of most preferable disease modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) patients.ObjectivesAim – prospective study of harm caused by subcutaneous MT to achieve target RA activity and inflammation control (within REMARCA trial protocol).Methods237 RA patients (with RA duration ≤6 mo (very early RA) – 101, >6 mo – 136) were administered subcutaneous MT (SC MT) as DMARD starting at 10 mg/week with further rapid dose increment up to 20–30 mg/week. All ITT (who received at least I MT injection) population was evaluated. Patients were monitored with monthly routine clinical, lab and instrumental examination, all adverse drug reactions (ADRs) were documented in a special standardized form by a physician. MT discontinuations (for up to 3 weeks, i.e. with total medication washout) and withdrawals were also registered. Randomly assigned 60 patients were filling questionnaires in order to better evaluate SC MT tolerability and patient's willingness to inject the drug continuously.ResultsMT–associated ADRs were registered in 49 (21%) patients: in 30 (61%) with very early RA and in 19 (39%) with RA >6 mo. Most common ADRs: increase of aminotransferases levels (ALT; 5,1%), (AST; 4,2%), nausea – 3,4%; post-dosing reactions (dizziness, BP increase) – 2,5%; alopecia – 2,1%; rash – 1,7%; injection site skin reactions in situ – 1,3%; infections requiring antibiotics or antiviral drugs, – 1,3%; leukopenia – 1,3%; less common: diarrhea – 0,8%; metallic taste in the mouth – 0,4%; remote from injection site soft tissue abscess/infiltrate – 0,4%. In 4,2% patients both MT-related and non-related ADRs led to SC drug withdrawal: rash (2,1%), post-dosing reactions (0,8%), nausea (0,4%), elevated transaminases (0,4%), leukopenia (0,4%). In these patients ADRs were not related RA duration.Only in 1% of patients SC MT was intolerable, while other patients classified SC MT as comfortable (42%) or tolerable (57%). 88% of responders were in favor of SC MT long-term use, the rest were either not willing (12%) or have not yet made their mind (1%).ConclusionsADRs associated with SC MT were registered in one of every 5 patients and led to withdrawal from SC MT in 4,2% RA patients. In 11% SC MT was discontinued due to ADRs, bat later restarted again. Obtained results allow to discuss the usefullnes of SC MT before administration of GEBA. This study has also established RA patients' compliance with continuous use of SC MT.Disclosure of InterestNone declared

BackgroundComorbid infections have significant impact on morbidity and mortality, especially in autoimmune diseases. Prevention of infection is an integral part of supervision of these patients.ObjectivesTo investigateimmunogenicity and safety of 23-valent polysaccharide pneumococcal vaccine in patients with rheumatoid arthritis (RA) treated with diseases modifying anti rheumatic drugs (DMARDs) and biologic diseases modifying anti rheumatic drugs (bDMARDs) during the 2-year follow-up.MethodsOut of 110 subjects (81 females (73,6%), 29 males (26,4%) aged 23–76 years) included into the study, 79 were RA patients and 31 were controls with a history of ≥2 episodes of lower respiratory tract infections (bronchitis, pneumonia). 52 patients with RA were on methotrexate (MTX), 14 were on leflunomide (LEF), 13 were ontumor necrosis factor alpha inhibitors (iTNF-α)+MTX. One dose (0,5 ml) of 23-valent polysaccharide pneumococcal vaccine was administered subcutaneously without discontinuation of MTX/LEF or 28–30 days prior to initiation of iTNF-α. Totally four study visits were preplanned: initial vaccination visit and 3 control visits in 1, 3 and 12 months after vaccinationfor 110 patients. 39 RA patients were followed up for 2 years (24 months). Routine evaluation during each visit included physical exams and laboratory tests. Levels of antibodies to pneumococcal capsular polysaccharide were measured using VaccZymeTM PCPIgG 2 kit (The Binding Site Group Ltd, Birmingham, UK). Post-immunization response coefficient was calculated for each participant as the ratio of AB levels during visits II, III, IV and V to baseline AB level at Visit I.ResultsNot a single caseof clinicallyor radiographically confirmed pneumonia was documented during the follow up period. Pronounced positive immune reaction after administration of the vaccine under investigation was documented in RA patients during different therapies, i.e., significant post-immunization response coefficient increase. There were 61% responders among RA patients and 70% responders among the controls during one-year follow-up. Dynamics of post-immunization response coefficient in RA patients during 2-year follow up are presented in the Table. RA patients and the control group are marked more than 2-foldsignificant increase in the content of antibodies in 3 monthsafter the vaccination. Despite the decline in their concentrationsto 12 months, it remained at the proper level and was increased to 24 month follow-up.Good tolerability of the vaccine was documented in 65% of cases, satisfactory (injection site pain, swelling and hyperemia of the skin up to 2 cm in diameter and subfebrilefever) in 35% of cases. As these reactions had no causal relationship with current RA therapy, and fully resolved within 24 hours without additional treatment, no RA therapy modification was required.Pronounced DAS28 positive dynamics in RA patients (4,27 and 2,68 at Visit I and Visit V, respectively, p<0,001) indicates the absence of any negative impact of vaccination on disease activity.ConclusionsT...

BackgroundThe Treat to Target (T2T) strategy in rheumatoid arthritis (RA) implies regular review of therapy in order to achieve the optimal outcome - remission or low disease activity (LDA). The majority of patients would require upgrade of therapy to drug combinations, including biologics. Prediction of the necessity of such upgrades is an important task for practitioners.ObjectivesTo identify factors, indicating the necessity of biologics in RA patients, treated in compliance with T2T strategy.MethodsThe REMARCA study (Russian acronym: Russian InvEstigation of MethotrexAte and biologics in eaRly aCtive inflammatory Arthritis) included patients with early and established active RA, not treated previously with subcutaneous methotrexate (SC MT) injections and biologics. Totally 264 pts were included, 161 out of them (29 males, 132 females, 50,3% with disease duration <6 mo., 84% RF(+), 82% anti-CCP(+), DAS28 5,47±1,14, SDAI 30,2±14,3) were followed up for at least 12 mo. All patients received SC MT as a fist-line therapy, starting from 10 mg/week with fast dose escalation up to 25-30 mg/week. Use of steroids was limited to continuation of previously administered low oral doses (in 15% pts) and intra-articular injections (2 doses per 3 mo). Therapy revision and initiation of biologics in combination with SC MT (adalimumab, certolizumab, or abatacept), was made every 3 mo (or more often if indicated) in order to reach T2T targets.ResultsThe T2T targets by Month 12 were achieved in 120 (74,5%) pts, including LDA (3,3