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). 

There has been significant progress in research focused on rheumatoid arthritis (RA) over the past decade. Nine innovative biologics agents – monoclonal antibodies and recombinant proteins inhibiting activity of the key proinflammatory cytokines and pathological activation of T and B cells involved in the development of the immune-inflammatory process – have been designed to treat RA. However, the radical improvement of prognosis in RA patients depends both on launching innovative drugs and refining the treatment strategy. This strategy is based on early diagnosis, which makes it possible to initiate the very early («window of opportunity drug») active and tightly controlled anti-inflammatory therapy aimed at achieving remission as soon as possible (the «Treat to Target» conception). The «Treat to Target» conception formulated by EULAR in 2010 has been widely incorporated in national guidelines on management of RA elaborated in many countries, including Russia. A new edition of EULAR recommendations was prepared in 2013; it has accumulated the scientific progress and clinical experience over the past three years. The publication is aimed at providing the general characteristics of the key provisions in the new recommendations and discussing some disputable problems that have not been solved yet and require further research. 

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 AllRussian public organization “Association of Rheumatologists of Russia”. 

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 inade- quately 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 funda- mental 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 complica- tions, 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.

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 antibody 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 subcutaneous 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 6and 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.