Rheumatoid arthritis (RA) is one of the most prevalent autoimmune diseases in humans and is a serious medical and social problem in the Russian Federation. Current synthetic and biological agents acting through specific molecular targets, play a significant role in the treatment of RA. Over the last few years, inhibitors of the biological effects of interleukin-6 (IL-6) have attracted increasing attention, being positioned as the first choice agents among the biologicals, especially if there is a need in monotherapy. IL-6 is a pleiotropic cytokine with a broad range of biological effects on immune cells, such as B and T lymphocytes, on hepatocytes, hematopoietic cells, vascular endothelial cells, and many others. In this regard, IL-6 is a good therapeutic target in RA. For several years, the group of inhibitors of IL-6 biological effects has been represented by one drug only, i.e. tocilizumab. The new drug of this group, sarilumab, is a human monoclonal antibody (IgG1 subtype) to the IL-6 receptor. Sarilumab binds specifically to both soluble and membrane IL-6 receptors (IL-6Rα), and inhibits IL-6-mediated signal transduction involving signal protein glycoprotein 130 (gp130) and signal proteins STAT-3. There is evidence that sarilumab has a higher affinity to the IL-6 receptor, and binds the receptor in a more stable manner than tocilizumab. Sarilumab has been approved for treatment of RA with moderate or high activity in adult patients with inadequate response or intolerability to one or several synthetic basic drugs, at a dose 150 mg or 200 mg subcutaneously biweekly in combination with methotrexate (MTX). It also can be prescribed as monotherapy in case of MTX intolerability or if treatment with MTX is inexpedient. Sarilumab is a highly active therapeutic agent with proven superiority in monotherapy over adalimumab. Therefore, sarilumab can be positioned as a first line biological agent in patients with high inflammatory activity, as well as in those resistant to tumor necrosis factor-α inhibitors. The safety profile of sarilumab is similar to that of tocilizumab; probably there is a slightly higher risk of neutropenia, but a lower risk of dyslipidemia, reactions at the injection site and gastrointestinal perforation for sarilumab than for tocilizumab.

Цель исследования. Изучение взаимосвязи аллелей гена HLA-DRB1 и полиморфизма TNFА(-308G>A) с деструктивным поражением суставов и его прогрессированием в течение 12 мес у больных с ранним ( A) генотипировали с помощью полимеразной цепной реакции в режиме реального времени (ПЦР-РВ). Полиморфизм гена HLA-DRB1 исследовали c использованием низкоразрешающего генотипирования PCR-RT c последующим секвенированием аллеля *04. К аллелям SE+ (Shared Epitope) относили аллели HLA-DRB1*01, *04:01, *04:04, *04:05, *04:08, *10. Результаты. Показано, что базовые значения числа сужений и общего счета по Шарпу у носителей генотипа GG гена TNFA почти в два раза превышали таковые у носителей генотипа GA (р A) независимо друг от друга ассоциированы с рентгенологическим деструктивным поражением суставов у больных с ранним, активным РА после 12 мес лечения согласно стратегии «Treat to target».

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk. The results of works on the impact of antirheumatic therapy on carotid artery (CA) intima-media thickness (IMT) are contradictory. Objective: to assess the time course of changes in CA IMT and CA atherosclerosis (CAA) in patients with early RA during treatment to target at a 18-month follow-up. Subjects and methods. The investigation enrolled patients with early RA (disease duration of less than 12 months), who had not previously taken disease-modifying antirheumatic drugs and glucocorticoids. Duplex scanning (DS) of the CA was performed with IMT measurement at baseline and at 18 months after treatment. Vascular atherosclerotic lesion was recorded when atherosclerotic plaque (ASP) was detected. Starting methotrexate (MTX) monotherapy was prescribed to all the patients, when it showed an insufficient effect at 3 months, a biological agent (BA), such as a tumor necrosis factor-α inhibitor or abatacept, was added. RA remission was noted in 31 (42%) patients at 18 months of treatment. Results and discussion. The investigation included 74 patients with early RA; whose median (Me) age was 56 years, all the patients had moderate or high disease activity (Me DAS28-ESR, 5.4). At baseline, there was increased CA IMT in 51.4% of cases and CAA in 55.4%. At 18 months of treatment, there were no significant IMT changes. New CA ASPs were recorded in 8 (24.2%) patients who had no CAA at the time of inclusion in the investigation (p < 0.05). Nineteen (46.3%) patients were recorded to have the progression that had been identified when including CAA as a considerable increase in the number of ASPs (p < 0.05). The risk of CAA progression was correlated inversely with the mean 18-month level of high-density lipoprotein cholesterol (HDL-Cmean) and directly with the mean concentration of C-reactive protein (CRPmean). There was no significant correlation between HDL-Cmean and CRPmean. The changes of CAA were unassociated with the value of DAS28-ESR, the achievement of RA remission, and antirheumatic therapy (MTX monotherapy, MTX + BA). Conclusion. CAA shows progress in patients with early RA despite they are treated to target. DAS28-ESR remission in RA and ongoing RA treatment option had no substantial impact on the course of CAA. HDL-Cmean and CRPmean are independent risk factors for progression of CAA.

The lecture presents the new EULAR clinical guidelines on the treatment of rheumatoid arthritis (RA) published this year. The new version of the recommendations is fully international, because for its creation, the largest group of experts in the history of the development of the EULAR recommendations was collected, including not only the representatives of the EU countries, but also Russia, Asia, North and South America. The main changes compared to the previous (2013) version are: approval of achieving sustainable remission as treatment goal; the possibility of changing the treatment schedule during the first 3 months, the feasibility of short-term use of medium and high doses of glucocorticoids; the possibility of using targeted synthetic (ts-) DMARDs (tofacitinib) as second-line drugs; the advantage of the combination of biologics and ts-DMARDs with synthetic (s-) DMARDs over monotherapy; the advantage of tocilizumab and ts-DMARDs over other drugs if necessary using in monotherapy.

This article presents results from two clinical trials of infliximab biosimilar, BCD-055, including comparative data on the pharmacokinetics (PK), efficacy and safety of BCD-055 and innovator infliximab (IFX) in patients with ankylosing spondylitis (AS). Objective : The purpose of phase I clinical study ASART-1 was to evaluate the pharmacokinetic and safety profile of BCD-055 and to prove its equivalence with Remicade®, phase III study ASART-2 was conducted to evaluate the efficacy and tolerability of BCD-055 in comparison with Remicade® in patients with active AS. Patients and methods : Both studies were conducted as international multi-center randomized double-blind studies in direct comparison with innovator IFX. Inclusion and exclusion criteria, main examination methods, and drug regimens were the same in both trials. A total of 199 patients were enrolled in the studies. After the screening, the patients were stratified by CRP and BASDAI score, randomized (1:1 ratio in ASART-1; 2:1 ratio in ASART-2) into 2 arms and received BCD-055 or innovator IFX at a dose 5 mg/kg IV at 0, 2, 6 and then every 8 weeks (up to week 54). The primary endpoint for PK profile evaluation was the area under the concentration-time curve (AUC(0-tau)), maximum serum concentration of infliximab at steady state Cmax,ss. Efficacy was assessed by achieving ASAS20 at week 30, the endpoints for safety profile were the incidence of adverse events and serious adverse events during the maintenance-dosing phase and withdrawals from the study due to the safety reasons. Results : A total of 81 patients (ASART-1 study) were included in PK analysis, 199 patients were in efficacy and safety analysis. AUC(0-tau) value were 25,420,996.25±11,635,015.74 (ng/ml) Cmax,ss for BCD-055 and 26,114,705.71±12,102,376.9 (ng/ml)⋅h for INF innovator (p>0.05). Cmax,ss for BCD-055/Remicade® was 122,752 [99,401–151,553] ng/ml and 119,844 [98,120–132,772] ng/ml, respectively (p>0.05). ASAS20 was achieved at week 30 by 81.30% of the patients in the BCD-055 group, and 67.74% in the INF innovator group (p=0.061). The analysis of secondary endpoints (BASDAI, BASMI, BASFI, MASES, quality of life, chest excursion, and number of pathologically changed joints) showed no difference between the biosimilar and innovator groups. BCD-055 and innovator IFX showed highly similar safety profiles in both studies without cases of unexpected toxicity. The rates of AEs were equivalent for both drugs and were 48.48% and 58.21% of patients in the BCD-055 and Remicade®, respectively. Conclusion : BCD-055 is found to be equivalent in terms of PK, and showed the similarity in efficacy and safety profile compared with innovator IFX in patients with active AS.

Objective : to compare the efficacy and safety of abatacept (ABC) in patients with different duration of rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 86 patients with previous inefficiency or intolerability of therapy with synthetic disease-modifying antirheumatic drugs (DMARDs), mainly with methotrexate, and/or biological agents (BAs), such as adalimumab, etanercept, rituximab, infliximab, certolizumab pegol, and tocilizumab. The patients were divided into 2 groups. Group 1 included 29 (34%) patients with early RA ( 2 years' disease duration). The patients' mean age was 49±13.4 years; most of them were women who had a high RA activity (the mean DAS28 value was 5.2±1.15), were seropositive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. All the patients underwent standard clinical and laboratory examinations. ABC was injected intravenously at a dose of 10 mg/kg according to the standard regimen. Every 3 months, disease activity was assessed with DAS28; functional status was evaluated with the Health Assessment Questionnaire (HAQ). Results and discussion. In the early and advanced RA patients, the mean DAS28 at baseline was 5.2±0.9 and 5.2±1.3, respectively. After 3 months of ABC treatment, it significantly decreased in both groups (p < 0.05). An improvement according to the criteria of the European League Against Rheumatism (EULAR) occurred in 76% of the early RA patients and in 74.5% of the advanced RA ones. Following 3 and 6 months of therapy, there were no significant differences between the two groups in the rate of a good response: the latter was obtained in 31 and 42% of early RA cases and in 25.5 and 40% of advanced RA cases, respectively. After 3 and 6 months, both groups showed a comparable number of those who did not respond to treatment (24 and 12.5% in the early RA group and 25.5 and 25% in the advanced RA group, respectively). During ABC therapy, both groups also displayed a significant decrease of HAQ disability index (DI) (p < 0.05). A total of 14 adverse events (AE) were recorded in 13 (15%) patients. The most common AE proved to be acute respiratory viral infections that were observed in 6 (7%) patients. Serious AE were seen in 3 (3.4%) patients. Conclusion. ABC therapy leads to decrease of RA activity in the majority of patients who have previously received ineffective therapy with DMARDs and BAs. There were no significant differences in good response rates according to the EULAR criteria between the advanced and early RA groups. Following 3 months of treatment, the decrease of HAQ DI was significantly more pronounced in the early RA group. AE were registered only in 15% of the patients. ABC has established itself as an effective drug that has a good safety profile and is able to occupy a niche in the therapy of both late and early RA.

Despite the advances in the therapy of rheumatoid arthritis (RA), which are associated with the use of biological anti-rheumatic drugs, the problem of effective treatment of RA is not still solved. Inclusion of new methods in treatment strategies, in particular the so-called «small mole cules», i.e. synthetic compounds acting on intracellular signaling pathways, such as Tofacitinib (TOFA) approved for use in rheumatologic practice, is very important. Objective: to evaluate the efficacy and safety of therapy with TOFA in combination with synthetic disease-modifying anti-rheumatic drugs (s-DMARDs), primarily methotrexate (MTX) in in patients with active RA in real clinical practice. Subjects and methods . This ongoing open-label trial is a part of the scientific program «Russian Investigation of Methotrexate and Biologics in Early Active Inflammatory Arthritis» (REMARCA) that explores the possibility of adapting the «treat-to-target» strategy in real prac-tice in Russia. The study included RA patients with moderate to high disease activity despite treatment with MTX or other DMARDs. A total of 41 patients with RA were included (8 males, 33 females; mean age 52.6±14.2 years, disease duration 47.2±49.7 months, 82.9% RF+ and 80.5% anti-CCP+,DAS28-ESR 5.45±0.95, SDAI 30.2±12.2). All the patients had previously received s-DMARDs; 12 (29.3%) patients also had biological DMARDs (1 to 4 biologics). Oral TOFA 5 mg in combination with MTX or leflunomide was administered twice daily to 40 and 1 patients, respectively, with the possibility of increasing the dose up to 10 mg BID. To date, 37 and 12 patients received TOFA for 3 and 6 months, respectively. Results. TOFA was used as a second-line drug (after s-DMARDs failure) in 29 (70.7%), as a third line drug (after s-DMARDs and biologics failure) in 12 (29.3%) patients. The dose was escalated to 10 mg BID in 13 (31.2%) patients, on the average, 11.2±1.7 weeks after treatment initiation. TOFA was not discontinued in the reporting period. There was a significant reduction in disease activity following just 4 weeks of TOFA therapy. At 3 months, 27% of patients achieved low disease activity (LDA) by the SDAI; 29.7% had SDAI remission; 35% had HAQ ≤0.5; at 6 months, LDA, SDAI remission, had HAQ ≤0.5 were seen in 41.7, 41.7, and 67%, respectively. There were no significant differences in the suppression of RA activity depending on whether second- or third-line TOFA therapy was performed. There were no serious adverse events (SAEs) or serious infections. Conclusions . Second- and third-line TOFA therapy allows the majority of patients to quickly achieve the T2T goals (56.7 and 83.4% of patients at 3 and 6 months, respectively), so the drug can be quite successfully «integrated» into the T2T strategy along with biologics. The drug effectively inhibits granulomatous inflammation (by the example of rheumatoid nodules) and shows a sufficient safety (no SAEs).

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.

Objective: to investigate the impact of treatment with subcutaneous methotrexate (MTX) and combined therapy with MTX and biological agents (BA) on the serum level of matrix metalloproteinase 3 (MMP3); to estimate the informative value of determination of MMP3 levels for predicting the clinical efficiency of therapy for early rheumatoid arthritis (RA). Subjects and methods. A total of 45 patients with early RA were examined. In all the patients, MTX as the first disease-modifying anti-rheumatic drug was subcutaneously injected at a dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. When the efficacy of MTX was inadequate, a BA was added [82% of the patients received adalimumab, 13% – abatacept, and 5% – other BA]; the follow-up duration was 1 year. Serum MMP3 levels were measured using an enzyme immunoassay before, 12 and 24 weeks after initiation of therapy. Results and discussion. After week 52 16 patients continued to receive monotherapy with subcutaneous MTX; BA were added to therapy in 29 patients in different follow-up periods. In the patients with early RA, the baseline MMP3 level was significantly higher than that in healthy donors: 46.7 [15.5; 64.5] and 7.74 [5.5; 11.8] respectively (p 54.6 ng/ml and the persistent higher level of this parameter 12 weeks after the initiation of treatment with MTX (> 25.1 ng/ml) were associated with lack of efficiency of MTX monotherapy after 52 weeks and with the necessity of using combined therapy [area under the curve (AUC), 0.78; 95% confidence interval (CI), 0.63–0.93 and AUC, 0.96; 95% CI, 0.54–0.86, respectively]. Conclusion. The high baseline MMP3 level (> 54.6 ng/ml) and the persistent increased level of this parameter 12 weeks after initiation of therapy with subcutaneous MTX (> 25.1 ng/ml) may be regarded as a likely predictor for the inefficiency of MTX monotherapy and for the necessity of using BA.

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 TNF α 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).

The current treatment strategy for rheumatoid arthritis (RA) is based on the principles of early aggressive therapy and tight control, which are summarized in «Treat-to-Target» recommendations. The draft RA treatment guidelines by the Association of Rheumatologists of Russia (ARR) reflect these principles in expanded form. Twenty-four ARR recommendations contain the detailed description of current treatments for RA, which relies on the principles of evidence-based medicine. Some practical issues for the management of patients with RA require special attention. The comparison of a number of randomized trials and the author’s experience in the REMARCA study may conclude that subcutaneous methotrexate (MTX) in an initial dose 10–15 mg/week with its fast increase up to 20Р30 mg/week is an optimal first-line therapy for RA. To choose the period within which a decision should be made on the incorporation of biologic agents (BA) in patients with an inadequate response to MTX is a serious matter. The experience gained in a number of clinical trials, particularly in those of etanercept, shows that a 12-week follow-up is sufficient in most patients. First of all, it is important for early RA. After achieving sustained remission, the reasonable tactics is to accurately reduce the dose of a BA although there may also be complete therapy discontinuation («treatment holiday») in the future.

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 ( R ussian Inv E stigation of M ethotrex A te and biologicals in ea R ly a C tive inflammatory A rthritis) 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.

Objective: to study the clinical efficacy, immunogenicity, and safety of a 23-valent pneumococcal vaccine in patients with rheumatoid arthritis (RA). Subjects and methods. The investigation enrolled 102 patients (78 women and 24 men, aged 23 – 70 years), including 72 patients with RA and 30 people without systemic inflammatory rheumatic diseases (a control group) who had a recent history of 2 and more cases of lower respiratory tract infections (bronchitis, pneumonia). When included, all the patients received anti-inflammatory therapy with methotrexate (MT) (n = 52), leflunomide (LEF) (n = 10), or MT + tumor necrosis factor-α (TNF-α ) inhibitors (n = 10). A single 0.5-ml dose of the 23-valent pneumococcal vaccine was administered subcutaneously during continuous MT or LEF therapy for the underlying disease or 3 – 4 weeks before the use of a TNF-α inhibitor. During control visits (1 and 3 months and 1 year after administration of the vaccine), the patients underwent physical examination and routine clinical and laboratory studies. Results. No clinical and radiological symptoms of pneumonia were recorded in any case during a 12-month follow-up. The RA and control groups showed a more than 2-fold increase in anti-pneumococcal antibody levels 1 year after vaccination. The vaccine was well tolerated by 67 patients. 27 patients were observed to have pain, cutaneous swelling and hyperemia and 8 patients had subfebrility. There were neither episodes of RA exacerbation nor new autoimmune disorders during the follow-up. Conclusion. The findings suggest that 23-valent pneumococcal vaccine shows a good clinical efficacy, adequate immunogenicity, and good tolerability in the patients with RA.

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.

Objective : to evaluate the safety of treatment with methotrexate (MT) solution for subcutaneous injections in patients with rheumatoid arthritis (RA). Subjects and methods . 237 RA patients enrolled in the study within the REMARCA protocol were given MT solution for subcutaneous injections (Metoject) to assess the standard parameters of therapy safety. Results. Overall, adverse events (AE) were noted in 49 (21%) patients. In 30 (30%) of them RA duration was less than 6 months (Group 1) and in 19 (14%) – more than 6 months (Group 2), in most cases average MT dose was 20.9±3.45 mg/week. Elevation of alanine aminotransferase and aspartate aminotransferase levels, nausea, postinjection reactions, alopecia, rash, infections, and leukopenia, were common (> 1%, but <10%); diarrhea, metallic taste in the mouth, soft tissue abscess/infiltration developing far from the injection site, were uncommon (the WHO term corresponding to 0.1–1%). AE required MT discontinuation in 4.2% of the patients. Conclusion. The results of the study allow discussing subcutaneous MT administration before treatment with biologicals, which makes it possible not only to reduce financial expenditures, but also to improve patient safety

DAS28 index calculated with regard for ESR, the number of swollen/painful joints and evaluation of the patient’s condition by VAS is universally used to estimate activity of rheumatoid arthritis (RA). There is a variant of calculation using C-reactive protein (CRP) instead of ESR. Our experience indicates that ESR decreases more slowly than CRP during treatment and better reflects dynamics of patients’ condition. From the practical standpoint it is important to estimate activity of RA because therapeutic modalities are chosen based on the DAS28 value. Aim. To study the influence of pharmaceutical form of methotrexate on the acute-phase response in rheumatoid arthritis. Materials and methods. The study included 32 patients (24 women, 8 men) aged 19-76 (mean 47.5+-28.5) yr with active RA (DAS28>3.2) 4-30 months (11.5+-7.4, median 8) in duration. Diagnosis was made using AXR criteria (1987), none of the patients previously received methotrexate injections. Inclusion criteria: initially high ESR (Westegren, mm/hr) and/or CRP (mg/l measured by a highly sensitive method). All patients were given methotrexate subcutaneously for 12 weeks as monotherapy (initial dose 10 mg, maximum one 25 mg/week). The cumulative dose was 211.36+-17.2 mg. Results. Side effects did not require withdrawal of methotrexate. CRP level decreased faster than ERS: a 70% decrease of CRP by week 12 was recorded more frequently than that of ESR. Slow dynamics of the number of swollen joints compared with CRP may be due to the low cumulative dose of methotrexate. Duration of the disease had no effect on dynamics of acute phase characteristics. Conclusion. Methotrexate injections resulted in markedly delayed development of clinical signs of improvement compared with laboratory values. CFP levels fell down much faster than ESR, Remission or low activity of RA (estimated from DAS28) occurred only in 38% of the cases after 3 month monotherapy by methotrexate injections. It is concluded that efficacy of this drug should be estimated no sooner than 4 months after the onset of the treatment.

In our previous publication, we reported the main provisions of the new EULAR recommendations (2013) and discussed some debating points of RA pharmacotherapy that require further research. The purpose of this article is to review the present-day knowledge concerning the use of methotrexate (MT), since according to the EULAR recommendations, “MT should be considered as the main component of the strategy of the first-line treatment of active RA”. In the context of EULAR recommendations, special priority was given to the discussion of MT administration in patients with early inflammatory (undifferentiated) arthritis (UDA) and early RA, efficacy of MT monotherapy and combined therapy, including, along with MT, the standard basic anti-rheumatic drugs (DMARDs) and genetically engineered biological drugs (GEBDs), the role of MT in the induction and maintenance of remission, including remission without treatment with GEBDs. A conclusion was drawn that administration of MT is required in all patients with early RA and probably in patients with UDA in case of high risk of the disease transformation into RA. Early administration of the subcutaneous form of MT improves the efficacy of RA treatment and should be a mandatory component of the intensive RA treatment strategies, regardless of the use of glucocorticoids and other standard DMARDs and GEBDs. In patients with high disease activity, who require administration of high dose of MT or different schemes of combined treatment, it is advisable to begin the treatment with the injectable form of MT rather than tablet one.

The 15th annual European Congress of Rheumatology took place in Paris in June 2014. Its program was extremely diverse and included a discussion of new data pertinent to the diagnosis and treatment of the most common rheumatic diseases and problems of their etiology and pathogenesis, personified therapy, and many others. The Congress focused on the problems of early rheumatoid arthritis (RA). A number of papers concerned the efficiency and safety of different therapy regimens for RA at its onset, the discontinuation of biological therapy after achievement of remission, and the maintenance of drug-free RA remission. The Congress discussed new results of the tREACH trial comparing three treatment regimens for early inflammatory arthritis: combined therapy with methotrexate (MT), sulfasalazine, and hydroxychloroquine in conjunction with intramuscular glucocorticoids (GC); combined therapy with these drugs in conjunction with oral GC; and MT monotherapy with oral GC. A large number of reports dealt with the use of tumor necrosis factor-α inhibitors, the evaluation of their immunogenicity, and the analysis of reasons for therapy discontinuation and adverse reactions. Some aspects of therapy with disease-difying antirheumatic drugs were discussed. A number of reports concerned the application of novel laboratory biomarkers for RA. Thus, sufficiently many new data that will be able to optimize therapy for common rheumatic disease, such as RA, were presented at the Congress.

Objective: to assess the relationship of the efficiency of adalimumab (ADA) therapy in early rheumatoid arthritis (RA) with the serum level of the drug and with the presence of antibody (Ab) to it. Subjects and methods. Serum concentration of ADA and Ab against it (μg/ml) were measured using an enzyme immunoassay in 25 patients with early RA before, 12 and 24 weeks after beginning of the therapy. All patients received the disease-modifying antirheumatic drug methotrexate and ADA 40 mg subcutaneously every other week. ADA was the first biological agent for all patients. Results . The patients were divided into the following groups: those with a serum ADA level of <2.85 (Group 1, n=7) and ≥2.85 (Group 2, n=13). After 24 weeks of treatment, Group 1 showed higher disease activity (DAS was 4.5 [3.3; 4.9]) and levels of acute-phase reactants (ESR, 44 [18; 57] mm/hr; C-reactive protein (CRP), 10.1 [4.9; 34.5] mg/ml) than Group 2 (3.5 [2.9; 3.9], 15.0 [6.0; 17.0] mm/hr, 1.9 [0.75; 6.7] mg/ml, respectively; p<0.05). Also, after 24 weeks of therapy, there was a negative correlation of ADA level and DAS28 (r=-0.46; p=0.04), CRP (r=-0.54;p=0.02) and ESR (r=-0.5; p=0.02). Anti-ADA Ab were found in 3 and 2 patients after 12 and 24 weeks, respectively. After 24 weeks of therapy, all patients with anti-ADA Ab exhibited no clinical effect. There were few unresponsive patients (11%) among those without anti-ADA Ab. Conclusion. In patients with early RA treated with ADA, its low serum level (<2.85 μg/ml) is associated with the higher clinical and laboratory measures of disease activity. After 12–24 weeks of ADA therapy, 10–12.5% of patients are found to have Ab to the drug and its production is associated with lower efficacy.