Rheumatoid arthritis (RA), juvenile arthritis, spondyloarthritis, including psoriatic arthritis, systemic lupus erythematosus (SLE), and other systemic connective tissue diseases, are the most severe chronic immunoinflammatory rheumatic diseases (IIRDs) that affect as high as 10% of the population. Substantial progress has been made in the treatment of IIRDs in the 21st century. The current Treat to Target (T2T) strategy for RA is to achieve remission as soon as possible. The main treatment goal is to improve quality of life, by controlling the symptoms of the disease, by preventing joint destruction and dysfunction, and by maintaining social possibilities. The most important way to achieve this goal is to inhibit inflammation and to evaluate the efficiency of treatment, by using the standardized activity indices and by choosing the appropriate treatment option. The widespread use of biological agents in combination with standard disease-modifying antirheumatic drugs could substantially enhance therapeutic effectiveness. A new class of medicaments (chemically synthesized small molecular weight agents) to treat RA has appeared. The point of their application is tyrosine kinases, primarily Janus kinase (JAK). The new era in the treatment of SLE and other IIRDs is associated with the design of the new class of drugs Р BLyS inhibitors. In the coming years, the main lines of researches by Russian rheumatologists will be to elaborate a strategy to prevent IIRDs; to introduce innovative methods for their early diagnosis and treatment (biological agents, JAK inhibitors, and other cell signaling molecules) and for the prediction of the outcomes of the most severe forms of IIRD; to realize the concept of personified medicine (to investigate the prognostic biomarkers of the efficiency and safety of targeted therapy), to reduce the risk of infectious complications, cardiovascular diseases, cancer, osteoporotic fractures, and other comorbidities.

Guidelines and recommendations developed and/or endorsed by the American College of Rheumatology (ACR) are intended to provide guidance for particular patterns of practice and not to dictate the care of a particular patient.
The ACR considers adherence to these guidelines and recommendations to be voluntary, with the ultimate determination regarding their application to be made by the physician in light of each patient’s individual circumstances.

Guidelines and recommendations are intended to promote beneficial or desirable outcomes but cannot guarantee any specific outcome. Guidelines and recommendations developed or endorsed by the ACR are subject to periodic revision as warranted by the evolution of medical knowledge, technology, and practice.

The American College of Rheumatology is an independent, professional, medical and scientific society which does not guarantee, warrant, or endorse any commercial product or service.

Proinflammatory cytokines involved in the pathogenesis of rheumatoid arthritis (RA) are able to inhibit the production of insulin and to cause insulin resistance in peripheral tissues. Conceivably RA increases the risk of developing carbohydrate metabolic disturbances (CMDs), such as diabetes mellitus (DM), fasting hyperglycemia (FH), and impaired glucose tolerance. Patients with a concurrence of RA and DM belong to a category of the most critically ill patients with a poor prognosis of macro- and microvascular complications.

Objective: to estimate the rate of CMDs (DM and FH) in a cohort of patients with RA and their possible impact on the course of arthritis.

Subjects and methods. The investigation enrolled 165 patients (28 men and 137 women) aged 55 [47; 61] years who were diagnosed with RA and followed up at the V.A. Nasonova Research Institute of Rheumatology. The patients who were seropositive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies were 86.3 and 78.8%, respectively. RA activity was low in 29.1% of the patients, moderate in 48.5%, and high in 22.4%. Glucocorticoids (GC) were taken at a mean dose of 5 [5; 7.5] mg/day by 40.6% of the patients; methotrexate, leflunomide, and genetically engineered biological agents were used by 72.7, 8.5, and 23.7%, respectively. A survey was conducted among the patients to find out their awareness of the presence of CMDs and fasting venous plasma glucose levels were determined to screen for hyperglycemia. Height and weight were measured and body mass index (BMI) was calculated.

Results. CMDs were present in 21 (12.7%) of the 165 patients with RA. Only 11 (6.7%) of the 165 patients were aware of having DM (2 cases with type 1 DM and 9 with type 2 DM); laboratory tests revealed CMDs in the remaining 10 patients (8 cases with FH and 2 with type 2 DM). The patients with DM and FH had a large number of tender joints (TJN) and high scores of general health survey (GHS) and DAS28 than those with normal blood glycose levels, but did not differ in RA duration, acute-phase indicators (erythrocyte sedimentation rate, C-reactive protein), and the number of swollen joints. Fifty-seven (34.5%) patients were overweight and 39 (23.6%) were obese. In the patients who took GC, glucose levels were lower (5.1 [4.7; 5.5]) than in those who did not (5.4 [5.0; 5.9] mmol/l; p = 0.001) and correlated with BMI ((r = 0.3; p = 0.01).

Conclusion. The investigation demonstrated the high rate of DM and FH in RA, but low patient awareness of these conditions, as well as the relationship of CMDs to arthritis activity mainly due to the changes of subjective indices (GHS and TJN). The intake of GC and BMI may affect blood glucose levels in RA.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory joint disease associated with impaired immune system performance. The specific features of JIA may be genetically determined.

Objective: to assess JIA activity in children with vitamin D receptor (VDR) gene ApaI and BsmI polymorphism genotypes.

Subjects and methods. The investigation enrolled 71 patients with JIA. When included in the investigation, all the patients were in an active state of disease. JIA activity was assessed using the most commonly used clinical and laboratory indicators, including the Ritchie articular index (RAI), JADAS10, JADAS27, JADAS71, CDAI, DAS, and DAS28. Molecular genetic studies determined VDR gene ApaI and BsmI polymorphisms by polymerase chain reaction, followed by restriction analysis.

Results. The boys who were carriers of a bb BsmI polymorphic marker in the VDR gene had a significantly higher activity of JIA measured by RAI (p=0.03), DAS (p<0.05), JADAS10 (p=0.04), JADAS27 (p=0.04), and JADAS71 (p=0.04) than those who were carriers of B allele (BB + Bb genotypes).

Conclusion. The carriage of the VDR gene bb BsmI genotype of the polymorphic marker is associated with high JIA activity, which may be regarded as a marker of poor prognosis in boys with JIA.

Chronic pain (CP) is an independent clinical syndrome that determines to the greatest extent dysfunction and lower social standing in a patient.

Objective: to assess quality of life (QL) in old patients with osteoporotic femoral fractures.

Subjects and methods. QL was assessed in 219 patients from an old age group (mean age 75.4±9.27 years) with osteoporotic proximal femoral fractures (a study group). A control group consisted of 200 examinees (mean age 71.5±10.39 years) without a history of fractures. QL was assessed using the SF-36 questionnaire. The results were presented in scores; moreover, a higher score denoted a better QL.

Results. In the patients with femoral fractures, the QL indicators were decreased to a greater degree and in the majority of parameters than in the control group. The least values were obtained in the following scales: physical functioning (41.94±31.16 scores) and role functioning caused by physical condition (42.34±27.2 scores). The patients with femoral fractures had significant limitations in all types of physical activity, at the same time they experienced severe pain and felt tired and vitality loss.

Chronic pain syndrome is shown to have impact on worse QL. The issues of combination therapy are discussed.

Low bone mineral density (BMD) is a risk factor of osteoporotic fractures. The RANKL–RANK–OPG system and some cytokines are known to play a role in the regulation of bone remodeling. Cytokines and osteoprotegerin (OPG) are able to affect the cardiovascular system. It is highly relevant to study the relationship between BMD and cytokine levels in patients with a concurrence of osteoporosis (OP) and coronary atherosclerosis.

Objective: to estimate the relationship between BMD and the level of cytokines and OPG in women having OP comorbid with coronary heart disease (CHD).

Subjects and methods. Sixty women (mean age 68.7±8.8 years) with OP comorbid with CHD (Group 1) were examined; a control group consisted of 38 patients (mean age 69.4±8.1 years) with isolated CHD (Group 2). BMD was measured in two regions: lumbar vertebrae (LI–IV) and proximal femur, by employing a DEXA densitometer (CHALLENGER, France). The serum levels of OPG, interleukin (IL) 1β, 4, 6, 8, 10, and tumor necrosis factor (TNF) α were determined by enzyme-linked immunosorbent assay (ELISA).

Results. The women with comorbidity were observed to have elevated IL6, 8, TNF-α, IL4, 10, and OPG levels. There was a negative correlation between IL1, TNF-α, and IL8 levels and vertebral BMD; OPG, IL4, 6, 8, and TNF-α concentrations were inversely related to femoral neck BMD. The independent factor of lower BMD was IL6 in the femoral neck and IL1 in the lumbar vertebrae. The findings suggest that there is a relationship between elevated cytokine levels and lower BMD in women having OP comorbid with CHD.

Objective: to estimate bone mineral density (BMD) in men with ankylosing spondylosis (AS).

Subjects and methods. Seventy-two male patients (mean age 43.2±9.1 years) diagnosed with extended- or late-stage AS (according to the 1984 modified New York criteria) (a study group) were followed up. A control group consisted of 70 apparently healthy men of the same age (46.7±1.9 years) with neither a history of bone fractures and no complains about osteoporosis (OP). In the study and control groups, BMD was determined by dual-energy X-ray absorptiometry.

Results. The patients with AS were found to have statistically significantly lower BMD in the femoral neck and lumbar spine. In the study group, osteopenic syndrome (OPS) was identified in 44 (61.1%): osteopenia (OPe) in 16 (22.2%) and OP in 28 (38.9%). In the control group, OPS was detected in 16 (21.62%) patients, OPe in 12 (16.21%), and OP in 4 (5.40%). Lower BMD was noted in both the femoral neck and lumbar spine in the extended stage of AS and only in the femoral neck in its late stage.

The sociomedical significance of osteoporosis is determined by its sequels (vertebral and peripheral skeletal fractures) that are responsible for high mortality and disability rates among persons in the old age group and accordingly for high material costs in the health care system.

Objective: to study sociomedical sequels and quality of life in patients with proximal femoral fractures in the old age group.

Subjects and methods. 956 patients with osteoporotic fractures were followed up. Major social sequels were traced in the patients 6, 12, and 24 months after femur fractures in relation to treatment options.

Results. There were 10 (8.0%) and 78 (66.7%) bedridden patients in the surgical and medical treatment groups, respectively. Twenty four months after fracture, recovery of function was noted in 72 (57.6%) and 32 (27.35%) patients receiving surgical and medical treatment, respectively.

Conclusion. The findings suggest that immediate and late sequels in patients with proximal femoral fractures depend on a treatment option.

The paper deals with the problems of optimizing the diagnostic criteria for idiopathic inflammatory myopathies (IIM), a group of heterogeneous rare autoimmune diseases characterized by inflammatory lesion in the skeletal muscles. The representatives of this group are traditionally considered to be polymyositis (PM), dermatomyositis (DM), and inclusion-body myositis. The authors detail the history of classification criteria for IIM from those proposed by T.A. Medsger et al. (1970) relying on its clinical picture, laboratory data and instrumental findings, as well as the criteria (including the first introduced exclusion ones) elaborated by A. Bohan and J.B. Peter in 1975, which remain fundamental in both clinical practice and researches. The basis for the clinical and serological criteria proposed by Y. Troyanov et al. (2005) for IIM is the identification of myositis-overlap syndromes. The classificational (subtype identification) and therapeutic value of the criteria based on clinical and serological characteristics was supported by the Hungarian investigators A. Vancsa et al. (2010) who investigated the relationship between the clinical and therapeutic characteristics of IIM and positivity for myositis-specific and myositis-associated antibodies. The criteria developed by M.C. Dalakas (1991, 2003) are based on the specific immunopathological features of a histological pattern, which allow the differentiation of DM, PM, and inclusion-body myositis from other myopathic syndromes. The 2004 European Neuromuscular Center (ENMC) criteria first identify necrotizing autoimmune myopathy and nonspecific myositis as individual subtypes. The serological classification of IIM, which is based on
the assessment of autoantibodies that play an important role in the pathogenesis of the disease, is of indubitable interest. There is an obvious need for the correct and timely diagnosis of both IIM as a whole and its subtypes in particular, which is complicated by the
heterogeneity of the latter. The proposed approaches to diagnosing and classifying IIM have their advantages and disadvantages so that work in this direction is yet to be under way.

The paper outlines the current views on mechanisms for pain development in osteoarthrosis (OA). The problem of analgesia in OA remains to be solved, which gives rise to a more careful study of the mechanisms in OA. Whether peripheral somatosensory nerve damage occurs in OA is the subject of careful investigation and dispute. The paper gives the results of studies of the neurogenic component of pain in OA patients. There is sufficient evidence for the presence of sensory anomalies accompanying pain in OA. The clinical use of questionnaires to detect neuropathic pain may assist in identifying central sensitization in patients with OA. Medicaments for the symptomatic therapy of pain are characterized.

The paper gives data on the positive role of hyaluronic acid (HA) preparations in the treatment of knee and hip osteoarthrosis (OA). The clinical effect of intraarticular agents is not only due to their lumbricative, but also, to a greater degree, anti-inflammatory and chondroprotective activities. The efficacy of HA preparations do not practically depend on their molecular weight. Long-term HA cycles can delay the risk of joint replacement in OA.

The paper summarizes the data of the GO-RAISE trial evaluating the efficacy and tolerability of golimumab (GLM) in patients with ankylosing spondylitis (AS). The trial was launched in 57 clinical centers of North America, Europe, and Asia in 2005. It enrolled 356 patients with high AS activity (BASDAI≥4) in whom previous and current therapies with nonsteroidal anti-inflammatory drugs (NSAIDs) or disease-modifying anti-rheumatic drugs were ineffective. Group 1 patients received subcutaneous placebo; Group 2 had subcutaneous GLM 50 mg; Group 3 took GLM 100 mg every 4 weeks. Concomitant therapy with methotrexate, sulfasalazine, hydroxychloroquine, glucocorticoids, and NSAIDs was continued in previous doses. The investigators have concluded that GLM therapy in patients with AS gives rise to a rapid clinical and radiographic response that persists for a long time. Although no comparative trials of GLM versus other tumor necrosis factor-α (TNF-α) inhibitors used to treat AS have conducted, the available data show that its efficacy and tolerability in these patients are similar to those of the TNF-α inhibitors already used in Russia. The GLM dose of 100 mg is noted to be worse tolerated than that of 50 mg with their practically equal clinical efficacy. The standard dose of GLM is 50 mg subcutaneously administered once monthly for all indications, including also for AS.

By taking into account the fact that there are a few alternative biological agents for the treatment of rheumatoid arthritis (RA), the cost of an annual therapy cycle using the agents is greater than that of high-technology surgical interventions, and a pharmacoeconomic study substantiating the optimal choice of a specific drug has been conducted. The pharmacoeconomic analysis has indicated the use of the biological agents etanercept (ETC) can decrease the cost of an annual therapy cycle for each patient with RA by an average of 84,764–481,622 rubles and considerably increase the number of patients receiving the current therapy without allocating additional resources. Switching 100 patents with RA to a treatment regimen including ETC enables 14–78% of the patient with this condition to be additionally treated within the framework of the same budget. The given results with regard to the data that there are significant differences in the efficacy and safety of biological agents used
to treat RA (National and EULAR guidelines for the treatment of RA, a number of meta-analyses of randomized controlled clinical trials) may conclude that the treatment regimen incorporating ETC is most preferential. The cost-effectiveness analysis based on the single meta-analysis proposed by G.J. Bergman et al., which had demonstrated differences in the efficacy of biological agents, also yielded the similar results. In this case, the administration of ETC is also more preferential because it can minimize expenditures of the health care system to achieve ACR20 and ACR50 responses. This advantage of ETC will cause the highest reduction in the number of hospital admissions, social benefits, and other expenses associated with the management of patients with RA. The authors are aware of the disadvantages of the performed trial, which cannot fully interpret uniquely the findings: the results of meta-analyses have limitations due to its low sensitivity in assessing the differences between the drugs; the virtually complete absence of published data on the direct comparison of the drugs, by employing sufficient patient samples, makes it necessary to use the data of the meta-analyses and to state that biological agents have similar efficacy and safety within the clinically permissible limit to recognize their equivalence; the trial has considered only an annual perspective to use the agents without regard for their therapy discontinuation rate and remission rate that requires that treatment should not be continued.