The paper discusses the common comorbidity of immune inflammatory rheumatic diseases (RD) and depression. It considers the causes and mechanisms, which are common to these diseases, namely, the provocative role of chronic psychosocial stress; neuroendocrine dysregulations of an immune response, which give rise to the hyperproduction of the proinflammatory cytokines determining the magnitude of the major clinical syndromes of RD and depression — chronic pain, fatigue, sleep disorders, functional insufficiency. The impact of depression on patient treatment adherence and efficiency and the course and outcome of RD is discussed. Particular attention is given to the timely therapy of depression in RD, to the effect of genetically engineered biological agents on depressive symptomatology, to the need for a personified approach to prescribing antidepressants. By taking into account the importance of detection and treatment of depressive disorders in rheumatologic practice from the clinical standpoint and in terms of medical, social, and economic consequences, the author propose an interdisciplinary approach to managing the patients with RD with the participation of rheumatologists, psychiatrists, neurologists, and medical psychologists.

Objective: to estimate quality of life changes in patients with rheumatoid arthritis (RA) while adding tocilizumab (TCZ) to therapy with disease-modifying antirheumatic drugs (DMARDs) and to study the efficiency and safety of the therapy in RA patients with an inadequate response to previous DMARD treatment. Subjects and methods. 201 patients with RA were examined. All the patients received six intravenous infusions of TCZ 8 mg/kg at a 4-week interval during stable therapy with DMARDs and glucocorticoids. The EULAR/ACR classification criteria and SDAI and CDAI were used to evaluate the efficiency of TCZ therapy. Remission was assessed by the EULAR criteria. Results and discussion. Prior to TCZ therapy, median [25th to 75th percentiles] DAS28 6.8 [6.1 to 7.4], SDAI 41.8 [34.6 to 53.7], and CDAI 39.2 [31.4 to 49.5] corresponded to high RA activity. At week 4 of TCZ therapy, there was a reduction in DAS28 (4.6 [3.8 to 5.4]), SDAI (24.6 [17.8 to 33.4]), and CDAI (23.6 [17.5 to 32.0]), which was retained until 24 weeks (р < 0.01). At week 24 of TCZ therapy, good and fair effects according to the EULAR criteria were observed in 133 (70.4%) and 54 (28.6%) patients, respectively; no effect was seen in 2 (1.1%) patients. The ACR20/50/70 effect was recorded in 89.1, 70.6, and 44.3% of the patients, respectively. EULAR and SDAI remissions were achieved in 51.3 and 21.4%, respectively. There were improvements in functional status and quality of life according to the EQ-5D and SF-36 questionnaires. C-reactive protein levels and erythrocyte sedimentation rate normalized 4 weeks after the first infusion of the drug and remained until week 24 of treatment. Conclusion. Thus, an analysis of the data of the Russian trial convincingly suggests that TCZ is effective and well tolerated in severe RA resistant to standard therapy with DMARDs.

Subjects and methods. 102 patients with early RA (79 women and 23 men; median age 51 years [41 to 62, 25th to 75th percentile]; disease duration 4 months [2.5 to 6.0]; DAS28 5.4 [4.1 to 5.9]) were examined. A comparison group consisted of 616 patients including 27 with systemic lupus erythematosus, 15 with Sjö gren’s syndrome, 25 with ankylosing spondyloarthritis; 33 with osteoarthritis, 20 with overlap syndrome, 9, 22, and 168 patients with gouty, psoriatic, and undifferentiated arthritis, respectively; as well as 297 healthy donors matched with the examinees for gender and age. The concentrations of 36 biomarkers were measured by an immunonephelometric method, enzyme immunoassay, and xMAP technology. The values of one variable from others were predicted using a multiple linear regression method (multivariate analysis). Results. The strongest predictors of early RA, such as the concentrations of interleukin-6, C-reactive protein, granulo-cyte-macrophage colony-stimulating factor, interferon-γ (IFN-γ), IFN^-inducible protein, anti-cyclic citrullinated peptide antibodies, were identified and a candidate for MDI was developed for early RA (MIRRA). After thorough validation, MIRRA may be regarded as a precision serological assay for the early diagnosis of RA. Conclusion. The development of MDI having a higher diagnostic precision than routinely used biomarkers is imperative for early RA diagnosis that allows one to initiate active antirheumatic therapy that is able to effectively delay progressive joint injury.

The international recommendations «Treat to target» (T2T) underline the greatest importance of treatment strategy for the success of treating rheumatoid arthritis (RA). Evaluation of the efficiency of this approach obviously requires special strategic studies with an adaptive design, which substantially differ from classical randomized clinical trials and are much closer to clinical practice. To date, there are only single publications on the practical application of the T2T recommendations, there is a problem in the choice of effectiveness criteria and there are a number of other important problems associated with the introduction of these recommendations. The Russian study REMARCA is to answer these questions. Its design focuses on the practical adaptation of the T2T strategy to treat patients with earlyand extended-stage active RA who have poor prognostic factors, by using subcutaneous methotrexate and genetically engineered biological agents (GEBA). Preliminary analysis shows that therapy according to the REMARCA protocol is successful in the majority of patients. The high rate of low RA activity and remission has been achieved during subcutaneous methotrexate monotherapy. The patients who need GEBA to be incorporated may be initially more resistant to therapy. The patients with early RA have better chances of successful T2T therapy than those with extended-stage RA.

Objective: To study the efficiency and tolerance of two pulse therapy regimens: combination pulse therapy with highdose methotrexate (MT) and high-dose dexamethasone and pulse therapy with dexamethasone. Subjects and methods. The trial enrolled 100 patients with early rheumatoid arthritis (RA) treated with two pulse therapy regimens and then followed up for 1 year during standard MT therapy. The efficiency of the treatment was evaluated using the ACR 20/50/70 criteria. The number of swollen and tender joints (SJ and TJ), erythrocyte sedimentation rate, C-reactive protein levels, systemic disease activity and a need for nonsteroidal anti-inflammatory drugs and glucocorticoids were determined. Results and discussion. After 1 month of therapy, the patients of both groups showed significant positive changes in all assessed parameters of RA activity. By this time, after combination pulse therapy with MT and dexamethasone, there was a more significant reduction in the number of SJ, total activity scores given by a patient and a physician, and pain intensity according to the visual analogue scale. By the end of 1and 3-month follow-ups, a 70% improvement was significantly more frequently noted in the combination pulse therapy group than in the monotherapy group. During a subsequent follow-up, the number of TJ and SJ tended to further decrease; however, the group differences were leveled. Evaluation of X-ray progression trends at 12 months of follow-up revealed no significant differences between the patients of the study groups. There were neither differences in the rate of adverse reactions nor severe complications. Conclusion. Combination pulse therapy with MT and dexamethasone was an effective and well tolerated option, the use of which could lower RA activity considerably, accelerate the therapeutic effect of MT, and reduce symptomatic therapy volume in the shortest possible time.

Objective: to define the significance of ultrasonography (USG) in the diagnosis of early destructive changes in the hand joints and the rates of rheumatoid arthritis (RA) progression in patients at different ages of disease onset. Subjects and methods. 100 patients with a valid RA diagnosis (American College of Rheumatology (ACR) 1987 criteria were examined. They were divided into 2 groups: 1) 11 patients with an early RA history of less than 2 years (ERA); 2) 35 patients with a RA history of over 2 years (LRA). Hand USG (Voluson-i GE; a 4-13-MHz linear probe; gray scale mode) was carried out at baseline and after 6-month follow-up. A sonographic index (US-Er-10) based on the bilateral evaluation of 5 articular areas, such as wrinkles, second-to-third metacarpophalangeal (MCP) and second-to-third proximal interphalangeal (PIP) joints, was proposed to evaluate the progression of destruction. According to US-Er-10 changes, the rates of development of the destructive process were arbitrarily separated into three categories: 1) slow progression rate; 2) moderate progression rate; 3) a rapidly progressive course. The X-ray parameters of structural progression were estimated at 12-month follow-up, by employing the Sharp method modified by van der Heide (SHS). Results. The USG versus X-ray detection rate of erosions was significantly higher in both ERA and LRA (p < 0.05). The ERA patients who had fallen ill after 55 years of age were found to have more significant baseline and final destructive changes according to a total SHS score (p < 0.05) and US-Er-10 index (p < 0.005) than those with RA onset at a younger age. In the ERA patients in whom US-Er-10 increased by three points or more at 6-month follow-up, the rates of X-ray progression at 12 months were significantly higher than those with less pronounced negative changes in this index (Δ total SHS score of 13.5 [3-23] and 0 [0-0], respectively; p < 0.05). The LRA group displayed no statistically relationships between the USG rate of erosion progression and the time course of X-ray changes and laboratory evidence. Conclusion. Hand USG reveals early erosive joint changes significantly more frequently than X-ray study and the high progression rate of destruction according to USG and the disease with onset after 55 years of age are associated with its severer course and poor prognosis in patients with ERA.

There has been a substantial expansion in the possibilities of current therapy for rheumatic diseases (RD) primarily due to the use of genetically engineered biological agents (GEBA). Objective: to evaluate the short-term efficacy and safety of GEBA in patients with different RD. Subjects and methods. The trial included all RD patients receiving GEBA: rituximab (RTM), infliximab (INF), adalimumab, etanercept, tocilizumab, abatacept in 2009-2012. Therapeutic efficiency and safety were evaluated 6 months later. The effect of GEBA was determined as “remission”, “improvement”, and “no response”, by using the parameters peculiar to specific diseases (such as BVAS, DAS28, BASDAI). Results. The trial enrolled 107 patients (49 men and 58 women; mean age 41.5 years) with rheumatoid arthritis (n=34), ANCA-associated vasculitis (n = 34), systemic lupus erythematosus (n=16), cryoglobulinemic vasculitis (n=11), ankylosing spondyloarthritis (n = 8), systemic vasculitis with large artery involvement (n=6), and other RD. All the cases showed severe systemic autoimmune disease refractory to standard immunosuppressive therapy. RTM (n=66) and INF (n = 31) were most frequently used. The high rate of RTM prescription was due to the fact that this drug was given to all patients with ANCA-associated vasculitis, systemic lupus erythematosus, and cryoglobulinemic vasculitis who totaled more than half of the patients included into the trial. The vast majority of them received GEBA for the first time. After the treatment, there was remission in 62 (57.9%) and improvement in 42 (39.3%) cases. Mild or moderate adverse reactions were observed in 22 (20.6%) patients and severe ones were seen in 6 (5.6%). Conclusion. GEBA therapy ensures a significant improvement in a substantial proportion of patients with different RD refractory to standard immunosuppressive therapy.

The countrywide detection and notification of ankylosing spondylitis (AS) are not only late, but are frequently not even done not least due to the undertraining of physicians in this area. Objective: to define a role of special educational programs for physicians in improving the diagnosis and registration of AS on the basis of its morbidity analysis. Subjects and methods. Two levels of spondyloarthritis (SpA) schools oriented to rheumatologists and other specialists were developed. Since late 2009, more than 40 schools have been arranged in different cities and towns of the country. The primary and overall morbidities of AS were studied using the data of the Ministry of Health of the Russian Federation from 2006 to 2011 inclusive: 2006-2008 were basic years (prior to SpA educational programs) and 2009-2011 are educational years. Results. In the basic years, the overall and primary AS morbidities varied within ±10%. However, there was their growing tendency just in the first year of SpA schools (2009), which persisted in the following year (2010). By 2011, the total number of AS patients increased by 2.4 times as compared to 2008; the number of first diagnosed patients did by more than 4 times. Conclusion. In the past years, the primary and overall morbidity of AS rose drastically, which is likely to be associated with the improved diagnosis of the disease due to the optimization of a diagnostic process and to the introduction of new diagnostic and therapeutic techniques. Special SpA education programs implemented in different regions of the country, by attracting more physicians of various specialties, play a significant part in the introduction of early diagnosis of AS.

The clinical manifestations of psoriatic arthritis (PsA) at its early stage may be inadequately informative. In this connection, radiological techniques, such as magnetic resonance imaging (MRI) and X-ray study of peripheral joints, in addition to clinical examination are of paramount importance in the diagnosis of early PsA. Objective: To compare the data of clinical examination and various imaging methods (MRI and X-ray) of the hand and foot joints in early peripheral PsA. Subjects and methods. The trial included 45 patients (14 men and 31 women; mean age 42.08±13.7 years; median PsA duration 1 year [range 0.55 to 2]) with early peripheral PsA without previous therapy with disease-modifying antirheumatic drugs (DMARDs), who met the CASPAR criteria (2006). A standard clinical examination was performed and the activity of peripheral arthritis and the presence of enthesitis and dactylitis were determined in the patients. Not later than 2 days after the clinical examination, a standard X-ray examination of the hands and feet in the direct projection and MRI of the same areas were made. Results. When included into the study, the entire group of patients was found to have a moderate PsA by DAS; its median was 3.12 [2.21 to 3.89]. Cutaneous PsA was noted in 40 patients; 5 persons had a family history of PsA; one female patient had ungual PsA only. In the study group, the clinical signs of enthesitis in the tendon attachments at different sites were revealed in 33 (75.3%) patients. Dactylitis was found in 34 (75%) patients. The clinical examination showed inflammatory changes in the hand and foot joints in 36 (80%) and 38 (84%) patients, respectively; while MRT revealed them in 31 (69%) and 32 (71%) patients. Hand MRI displayed arthritis of the proximal interpha-langeal (PIP), metacarpophalangeal (MCP), and distal interphalangeal (DIP) joints in 27 (87%), 21 (68%), and 12 (40%) of the 31 patients, respectively. Foot MRI exhibited MCP, PIP, and DIP joint arthritis in 26 (81%), 21 (66%), and 18 (56%) of the 32 patients, respectively. MRI revealed axial injury of the finger and toe joints in 45% (14/31) and 15.6% (5/32). The clinical examination established finger and toe flexor tenosynovitis in 17 (37.7%) and 5 (11%) patients, respectively; whereas MRI detected them significantly more frequently in 22 (48.8%) and 24 (53.3%) patients (Fisher test; p = 0.035). X-ray study disclosed erosions of hand and foot joint surfaces in 20% and during MRI this indicator was significantly higher than 24.4% (Fisher test; p = 0.022). Conclusion. The findings suggest that MRI of the hand and foot joints is one of the modalities to improve the early diagnosis of PsA. It can effectively reveal soft tissue pathology characteristic for this disease, as well as destructive changes in the hand and foot joints.

In patients with rheumatoid arthritis (RA), bone fractures occur 1.5-2 times more frequently than in the population. They often lead to reduced quality of life, to disability and death in the patients. It should be noted that risk factors (RFs) for fractures have not been studied on a sufficient sample in Russia; there are no recommendations on the prevention of fractures in this category of patients. Objective: to compare groups of RA patients with and without a history of fractures to further identify possible RFs for fractures. Subjects and methods. The trial included 254 patients aged 18 to 85 years, diagnosed with RA, from the database of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment», who had been followed up in 2010 to 2011. The patients were divided into two groups: 1) 101 (39.8%) patients with a history of low-trauma fractures and 2) 153 (60.2%) patients without a history of fractures. In Group 1, the patients were older than in Group 2 (mean age 59.8 and 56.1 years, respectively). Menopause was recorded in 88.1 and 77.8% of cases, respectively. The groups differed in the duration of RA an average of 15.5 and 11.5 years, respectively Results. The fractures in the history were associated with the use of glucocorticoids (GC), their higher cumulative dose and use duration. In Group 1 patients, the bone mineral density (BMD) was lower in all study skeleton portions and more frequently corresponded to osteoporosis. RA complications, such as amyloidosis and osteonecrosis, were more common in the patients with a history of fractures. Conclusion. In RA patients, the most likely RFs of fractures are age, the long-term intake of large-dose GC, low BMD, the severe course of RA, and the presence of its complications.

This review deals with arterial wall stiffness in rheumatic diseases. It shows a role of inflammation in the pathogenesis of increased vascular stiffness, considers its mechanisms at the level of altered cell components, the clinical signs of an inflammation-arterial stiffness association and the possibilities of its reduction, and a search for novel therapeutic strategies to diminish the stiffness of arterial vessels with antirheumatic drugs.