Authors report new recommendations of All-Russian Public Organization «Association of Rheumatologists of Russia» (ARR) on treatment of rheumatoid arthritis (RA), which adapts contemporary concept accepted in the respective field of pharmacotherapy known as «Treat to Target». According to it, the main objective of RA pharmacotherapy
is a remission (or low disease activity). To achieve it, disease modifying anti-rheumatic drugs (DMARD) should be administered to all RA patients as early as possible, with efficacy monitoring and therapy correction according to the disease activity. Special attention has been paid to the use of methotrexate (MTX) as «the gold standard» of RA pharmacotherapy and the key component of «Treat to Target» strategy. Early MTX administration (including subcutaneous injections) should become an obligatory component of RA treatment at all stages of the disease. If MTX is not efficient or not well tolerated (including subcutaneous form of the drug) as monotherapy or combined with conventional DMARD, biological agents should be used. Those include TNFα inhibitors, antagonist of interleukin-6 receptor (Tocilizumab), anti-B-cell drugs  Rituximab) and agents blocking T-cell activation (Abatacept). Tofacitinib therapy (JAK inhibitor) is indicated in patients who are resistant to conventional DMARDs and biologics. All biologics and Tofacitinib are more effective in combination with MTX (or other DMARD).

Despite major advances in the management of rheumatoid arthritis (RA), whicare associated with the development of new methods for its early diagnosis, the clinical introduction of a wide range of innovative medications and particularly the improvement of a strategy for their use, glucocorticoids (GC) still remain the most important  component of pharmacotherapy for this disease in real clinical practice. This publication that is a continuation of a series of papers devoted to the discussion of the main points of the 2013 European League against Rheumatism (EULAR) guidelines for the treatment of early RA, deals with the place of GC. An analysis of available data suggests that GC should be reserved for patients showing a high activity of the inflammatory process and having factors associated with a poor prognosis, but also, in the absence of risk factors for adverse events (AE), of course, contraindications to GC therapy. Throughout the use of GC, their AE should be meticulously monitored in compliance with the EULAR guidelines. It is anticipated that the wider use of combined therapy with methotrexate and a GC in earlyRA will be able to improve its prognosis in at least some patients and to cause a substantial decrease in the burden of disease, by reducing the risk of disability and the needs for expensive biological agents and joint replacement. All this confirms that it is relevant to include the proposition for using GC into the 2014 Guidelines for the management of rheumatoid arthritis of the All-Russian public organization “Association of Rheumatologists of Russia”.

The paper presents the materials of the Russian Arthritis Registry (OREL) that includes 3276 patients from 11 Russian Federation's largest research-and-practical centers situated in Moscow, Saint Petersburg, Novosibirsk, Kazan, Tula, Yaroslavl, Tyumen. It discusses the main goals of setting up registries, compares the results of an analysis of the data available in the Russian Registry OREL and registries of European countries and the USA. The findings suggest that there is non-uniform information on clinical, laboratory, and instrumental parameters in the national registers of a number of European countries and the USA. According to its basic characteristics, the Russian Registry OREL compares favorably with a number of other registries in the completeness of data collection, which allows a general idea of rheumatoid
arthritis (RA) patients in Russia. For further development of the OREL Registry, it is necessary to concentrate our attention on the following main areas: to improve the quality of filling out documents; to follow-up patients receiving different RA therapy regimens according to the guidelines of the Association of Rheumatologists of Russia for the treatment of RA; to conduct in-depth studies of comorbidity, primarily depressive disorders; to analyze adverse reactions that make RA therapy difficult; to actively use modules for patients' self-rating of their condition; to develop nursing care, etc.

To introduce treat-to-target recommendations is an important task of modern rheumatology; however, there is still a diversity of serious problems relating to a scientific rationale and a clinical one for this strategy and to the possibilities
of its implementation in real clinical practice, in the rheumatology service of the Russian Federation in particular, by taking into account the specific features of funding for high-tech medical care.
Objective: to determine the efficiency and safety of combined therapy with subcutaneous methotrexate (MT) and biological agents (BA) when using the treat-to-target strategy in patients with active early and extended-stage rheumatoid arthritis (RA) who have risk factors for a poor prognosis.
Subjects and methods. The results of the REMARCA (Russian InvEstigation of MethotrexAte and biologicals in eaRly aCtive inflammatory Arthritis) trial of 130 patients followed up for 12 months or more were given. There was a female preponderance; mean age 48.9±13.9 years, rheumatoid factor positivity (86.9%); anti-cyclic citrullinated peptide anti body positivity (89.2%). Seventy patients formed a subgroup of early RA (disease duration ≤6 months (mean 4.17±1.39 months)); 60 patients were a subgroup of advanced-stage RA (disease duration >6 months (mean 30.8±32.7 months)). In all the patients, therapy was initiated by using subcutaneous MT with its rapid dose escalation up to 20–30 mg/week and the achievement of the treatment goal (low disease activity or remission) was checked every 3 months and depending on the result a decision had been taken to add or not to add a biological agent (BA) (a tumor necrosis factor inhibitor or abatacept). If the former was insufficiently
effective, it was substituted for a BA from another class.
Results. Subcutaneous MT monotherapy provided remission or low disease activity in 49 (37.7%) patients; a BA was given to 81 (62.3%) patients. Following 6 and 12 months, low activity or remission according to SDAI was observed significantly more frequently in the patients who continued  ubcutaneous MT monotherapy than in those who received combined therapy with MT and BA. The similar results were obtained by using DAS28 and CDAI to assess a trend in disease activity. After 6- and 12-month follow-up, there was a significantly more marked decline of tender joint count, SDAI and CDAI in early RA than in advanced-stage RA; at 12 months, SDAI remission rate was
45.7% and 28.3%, respectively (p=0.047).
Conclusion. The treat-to-target strategy should be used in real clinical practice
and can yield spectacular results. Active therapy with subcutaneous MT with its rapid dose escalation to the maximally tolerable dose allows identification of a considerable group of patients (38%) with a good response to MT monotherapy.

The aim of a treat-to-target (T2T) strategy is to achieve a remission or minimal disease activity (MDA).
Objective: to investigate the efficiency of the T2T strategy for early psoriatic arthritis (ePsA).
Subjects and methods. Twenty-three patients (8 men and 15 women) with ePsA, who met the CASPAR criteria (mean age was 39.1±10.6 years; the median duration of ePsA was 7 [4; 24] months and that of psoriasis was 36 [12; 84] months), were examined. At the patient inclusion and then every 3 months, the investigators assessed the activity of ePsA by DAS and DAS28 and that of psoriasis by BSA (%) and PASI and determined erythrocyte sedimentation rate (ESR) (mm/h), C-reactive protein (CRP) level (mg/l), HAQ. All the patients received monotherapy (MoT) with subcutaneous methotrexate (MTX) (methoject) in a dose of 10 mg/week that was increased by 5 mg every 2 weeks until 20–25 mg/week was reached. The number of patients who had achieved remission (DAS <1.6 or DAS28 ≤ 2.4), low disease activity (LDA) (1.6 ≤ DAS <2.4 or 2.4 < DAS28 ≤ 3.6), MDA, and 20%, 50%, and 70% improvements according to the American College of Rheumatology (ACR) criteria. When LDA/MDA or remission was absent at 3 months of treatment, combined therapy (CoT) with MTX and adalimumab 40 mg once two weeks was used.
Results. The baseline median DAS was 3.97 [3.07; 4.67]; DAS28 – 4.33 [3.68; 4.73], PASI, 6 [3.1; 9.7]; BSA, 1 [0.5; 3.65]; CRP, 15 [8.6; 25.1] mg/l; ESR, 15 [8.6; 25.1] mm/h; and HAQ, 0.75 [0.63; 1.25]. After 3 months of MoT, remission defined by DAS and DAS28 was in 13/22.7% of the patients; LDA in 21.7/27.3%, and MDA in 26.1%,
respectively. ACR 20, 50, and 70 responses were obtained in 65.2, 26.15, and 8.7% of the patients, respectively. There were significant decreases in the level of CRP (to 5.7 [2.3; 10.7] mg/l), HAQ (0.38 [0; 0.87]), BSA (1 [0.3; 2]), and PASI (7.1 [0; 32.5]). ESR remained substantially unchanged (18 [10; 26] ml/h). Four patients with persistent high disease activity were given CoT; 19 patients continued MTX MoT. After 6 months, DAS/DAS28 remission was in 34.8/39.1% of the patients; DAS/DAS28 LDA in 26.1/39.1%; and MDA in 47.8%, respectively. ACR 20, 50, and 70% improvements were seen in 73.9, 60.9, and 47.8% of the patients, respectively. There were significant reductions in the level of CRP (4.9 [0.9; 8.3]), HAQ (0.13 [0; 0.63]), and BSA (0.35 [0; 1.6]). After MTX MoT, DAS/DAS28 remission was observed in 36.8/36.8% of the 19 patients; LDA in 15.8/36.8%; and MDA in 47.4%. ACR 20, 50, and 70 responses
were seen in 68.4, 52.6, and 42.1% of the patients receiving MTX MoT and in 100, 100, 75% of the patients (n = 4) having CoT, respectively; MDA was noted in 50% of the cases.
Conclusion. The use of the T2T strategy during a 6-month period could provide ACR 70 response and MDA in half of the patients and remission in one third of the patients with ePsA.

As new effective biological agents (BAs) are being widely introduced, in the past decade there have been serious changes in the rheumatoid arthritis (RA) strategy: its basis was the treat-to-target concept. It is emphasized that the basic strategy component is active early aggressive therapy with methotrexate (MT) and, if MT monotherapy is inadequately
ineffective, combined therapy with MT and standard disease-modifying antirheumatic drugs or MT and BAs. Although oral MT is more frequently prescribed in randomized placebo-controlled trials (RPCTs) and in clinical practice, there is now a tendency towards the wider use of its subcutaneous formulation. Novel evidence from fundamental studies dealing with the deciphering of the mechanism of MT action and the materials of numerous RPCTs,
observational studies, and national registries substantiate the unique place of MT in the treatment of RA, its complications, and comorbidities. The purpose of the review is to analyze new data on the mechanism of action of MT and its clinical efficacy and safety in rheumatology.