Репозиторий Университета

© 2018 Russian Electronic Journal of Radiology.All Rights Reserved. The incidence of hip osteoarthritis and degenerative lumbar spine stenosis increases with the lifespan. The combination of these two conditions is not rare and is known as “hip-spine syndrome” in literature. Due to the similarity of symptoms the main problem is to determine the primary pain generator. Solving this diagnostic problem can lead to proper treatment, surgical or other. Purpose. To provide the literature review of the hip-spine syndrome. Materials and methods. We analyzed articles published on https://www.ncbi.nlm.nih.gov/pubmed during 2004-2018 searching for keywords: «radiographic and clinical hip osteoarthritis» - 1141 results, «lumbar spine stenosis and MRI canal» - 521 results and «hip-spine syndrome» - 35 results, 54 items were chosen due to the objective. Results. Primary source of pain for patients with hip-spine syndrome often remains unclear. The existing diagnostic algorithms are imperfect, about 25% of patients do not feel relief of pain after spine surgery or total hip arthroplasty. Mandatory x-ray examination in case of unknown source of pain is important and can show changes in hip and lumbar spine. That can help to change the way of search for pain generator Conclusion. It is necessary to create new diagnostic algorithms that will be harmless for patients and will be with maximum value for surgeons.

© 2018 Universiteit Gent. All Rights Reserved. Due to the recent introduction of golimumab into paediatric rheumatology practice, an overview of the clinical studies of this tumour necrosis factor alpha inhibitor, most of which were conducted with adult patients with rheumatic diseases, has been presented. Clinical laboratory effects and tolerability of golimumab in the form of subcutaneous injections have been analysed for rheumatoid arthritis, psoriatic arthritis, and spondylitis. Evaluation of the efficacy and tolerability of golimumab in long-term observational studies (up to 5 years) has been discussed.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Infections are the main cause of death for patients with autoimmune rheumatic diseases. In adult patients with rheumatoid arthritis (RA), mortality caused by respiratory infections is 2-5 times higher than in the population. One of the frequent infectious complications in the course of treatment with tocilizumab, the first-choice drug for treating systemic juvenile idiopathic arthritis (sJIA), is pneumonia characterized by a poor clinical picture, normal values of laboratory indices of the disease activity (ESR, C-reactive protein) with pronounced changes in the lungs revealed by computed tomography. In case of acute respiratory infection in children with systemic JIA, immunosuppressants and genetically engineered biological preparations (GEBP) are discontinued. This often leads to an exacerbation of the underlying disease and the progression of a pathological process. At present, vaccination against pneumococcal infection in Russia is not included in the standard for managing patients with rheumatic diseases. Studies of the safety and efficacy of vaccination with 13-valent pneumococcal conjugate vaccine (PCV) in patients with sJIA receiving genetically engineered biological preparations were not conducted. Clinical Case Description. The article shares the experience of vaccination of a girl aged 9 years with a 13-valent PCV that was conducted in the course of a scientific investigation, which studied the efficacy and safety of vaccination of children with systemic JIA prior to prescription of GEBP tocilizumab. Vaccination did not cause a deterioration in the course of the main disease (1 month), led to a reduction in the incidence of acute respiratory infections (from 4 to 1 time within 6 months before and after vaccination), and discontinuation of antibacterial drugs within 6 months after vaccination. Conclusion. The safety of a 13-valent PCV in a child with sJIA and a decrease of the incidence of respiratory diseases after vaccination, their complications, and the use of antibacterial drugs have been shown.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Background. Insufficient efficacy or intolerance of the first TNF-α inhibitor in patients with juvenile idiopathic arthritis (JIA) is an indication for the appointment of a second inhibitor. Golimumab is a new TNF-α inhibitor registered for treating JIA under pediatric indications. Clinical Case Description. At an early age, the patient had an onset of polyarticular JIA. Due to the aggressive and rapidly progressive course, failure of therapy with nonsteroidal anti-inflammatory drugs, methotrexate and glucocorticosteroids for intra-articular administration, infliximab was prescribed to the patient, with a positive effect. Subsequently, the patient developed a secondary resistance to infliximab, inflammatory changes in the joints relapsed; thus, a second TNF-α inhibitor (golimumab) was prescribed. In the course of therapy, pain and signs of arthritis in the patient were reversed, and the range of motion in the affected joints increased. After one year of therapy, JIA remission was ascertained. At the same time, the child was not administered oral glucocorticosteroids. The duration of remission of the joint syndrome was 5 years. Adverse events were not serious and did not constitute a basis for drug discontinuation. Conclusion. Switching to a second TNF-α inhibitor (golimumab) was effective in a patient with a secondary resistance to the first TNF-α inhibitor.

© 2018 Voprosy Sovremennoi Pediatrii - Current Pediatrics. All rights reserved. Abstarct:-Background. An important goal of treating patients with juvenile idiopathic arthritis (JIA) is to achieve the best quality of life associated with health. Objective. Our aim was to assess the impact of methotrexate plus etanercept therapy on the quality of life of patients with early and late JIA. Methods. The prospective study included patients with early and late JIA without systemic manifestations. The patients' quality of life was assessed with the help of questionnaires for children and parents: the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scale, the Pediatric Quality of Life Inventory (PedsQL) Rheumatology Module, and the Health Utilities Index Mark 3 (HUI3). The quality of life was assessed prior to the therapy and after one, six, and 12 months of treatment. Results. 150 children with JIA aged 5.1 (2.0; 17.7) years; 50 children aged 4.0 (2.3-11.4) years in the group of etanercept monotherapy, 50 children aged 5.0 (3.2-9.0) years in the group of methotrexate monotherapy, and 50 children aged 9.9 (6.4-13.0) years in the group of methotrexate plus etanercept combination therapy. All groups showed low scores on all questionnaires before treatment, compared to healthy children. In the course of therapy, there was a tendency for score increase to almost 1.0 according to the HUI3 questionnaire in all groups. After one year of etanercept therapy, the parameters of the quality of life of children with early JIA did not differ from healthy children; the score increased from 56 to 90 p = 0.942 according to the physical functioning scale and from 60 to 85 p = 0.889 according to the emotional functioning scale. In the 2nd group, there was a tendency for score increase, but a statistically significant difference was found across all scales of the questionnaire. After 12 months of etanercept plus methotrexate combination therapy in patients with late JIA, the questionnaire analysis showed that the responses of healthy children and children with JIA differed with probability p = 0.001 for the physical functioning scale, p = 0.001 for the social functioning scale, p = 0.001 for role functioning, and p = 0.001 for the total score. The score increase from 60 to 85 p = 0.789 was noted for emotional functioning scales. Conclusion. The use of questionnaires to assess the quality of life in children with severe chronic diseases can significantly improve the efficacy of treatment and ensure its control.

© 2018 Russian Electronic Journal of Radiology. All rights reserved. Purpose. Purpose of the study is to have a detailed examination and investigation of the patient with all the required parameters. Material and methods. Revision knee replacement prosthesis making a difference in treatment outcome. Results. The result after the sleeve operation was uneventful and the patient had no complaints or pain even after a year of surgery. Conclusion. Long term complications are comparatively less when a proper prosthesis is selected for the particular patient operation.

© 2018 Media Sphera Publishing Group. All rights reserved. According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CÀNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative antiinflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.

© 2018 Media Sphera Publishing Group. All rights reserved. Objectives: To study efficacy of treat-to-target (T2T) strategy in early peripheral psoriatic arthritis (EPsA) after one year of treatment. Methods: 44 (M/F - 18/26) DMARD-na?ve patients (pts) with active EPsA, according to the CASPAR criteria, mean age 37.5±11.3 years, PsA duration 7 [4; 24] months, psoriasis duration 36 [12; 84] months, disease activity index (DAS) 3.78 [3.18; 4.67], DAS28 4.33 [3.67; 4.8] study were included. At the baseline and every other 3 months for total 12 months of therapy all pts underwent standard clinical examination, tender joint count (TJC), swollen joint count (SJC), patient pain VAS, patient/physiciańs global disease activity VAS, enthesitis by Leeds Enthesial Index (LEI)+Plantar Fascia (PF), dactylitis, Psoriasis Area Severity Index (PASI), body surface area (BSA), Health Assessment Questionnaire (HAQ), DAS, DAS28-C-RP, C-RP (mg/l). The dose of MTX s/c was escalated by 5 mg every 2 weeks from 10 mg/wk to appropriate dose 20-25 mg/wk according to the drug intolerance. If pts does not achieve the lower disease activity (LDA), MDA or remission after 3 months of MTX subcutaneous (s/c) mono-therapy, then combination therapy of MTX+Adalimumab (ADA) by standard regime was continued up to one year. At 12 months of therapy the proportion of pts who attained LDA by DAS/DAS28 or remission by DAS<1.6/DAS28-C-RP<2.6 or MDA, ACR20/50/70, PASI75 and dynamics of HAQ, LEI+PF, dactylitis were calculated. Mean±SD, Me [Q25; Q75], %, Friedman (Fr.) ANOVA, U-test, Wilcoxon test were performed. All p<0.05 were considered to indicate statistical significance. Results: At one year of treatment according to T2T strategy significant improvements disease activity and physical health function related to quality of life was seen. By 12 months of therapy remission by DAS and MDA was reached 61.4%/65.9% of pts accordingly. By 12 months of therapy ACR20/50/70 was seen in 88%/77%/59% of pts. In pts with BSA≥3% (n=16) at baseline psoriasis improvements by PASI75 was seen in 88% of pts. In 55% of active EPsA pts MTX (s/c) mono-therapy was an effective treatment. Conclusions: One-year treatment according to T2T strategy significantly improves all PsA clinical domains - Arthritis, dactylitis, enthesitis, skin psoriasis and quality of life despite of type of treatment. It seems that T2T is a useful strategy in EPsA but additional research concerning its implementation in real practice are needed.

© 2018 Ima-Press Publishing House. All rights reserved. Atherosclerosis is now considered as chronic inflammatory vascular disease connected to «pathological» activation of innate and adaptive immunity, characterized by lipid deposition, leukocyte infiltration and proliferation of vascular smooth muscle cells. Subclinical (low grade) inflammation plays fundamental role at all stages of atherosclerotic process progression and determines cardiovascular catastrophes development and mortality. Proinflammatory cytokines including interleukin (IL) 1, IL6, tumor necrosis factor α (TNFα), IL17, IL18, IL27, IL33, IL37 tightly interacting within cytokine network occupy an important place among numerous mediators participating in immunopathogenesis of atherosclerosis and rheumatoid arthritis. IL1β playing an important role in the development of many acute and chronic immunoinflammatory diseases attracts particular attention. IL1β significance in the development of atherosclerosis is determined by many mechanisms including procoagulant activity, enhancement of monocytes and leucocytes adhesion to vascular endothelium, vascular smooth muscle cells growth and others. Fundamental role of inflammation in the development of atherosclerosis is well proved in investigations of anti-atherosclerotic effect of canakinumab. Randomized placebo-controlled trial CANTOS (Canakinumab ANti-inflammatory Thrombosis Otcomes Study) assessing efficacy of canakinumab as new tool for secondary prophylaxis cardiovascular complications in general population of patients with severe atherosclerotic vascular damage. CANTOS results in combination with accumulated in rheumatology data on cardiovascular effects of anti-inflammatory drugs are of great importance for personification of approach to secondary prophylaxis of caused by atherosclerosis cardiovascular complications. They also contribute to the development of inflammatory theory of atherosclerosis pathogenesis in the whole.

© 2018 Ima-Press Publishing House. All rights reserved. The paper considers the modern concepts of the etiology and pathogenesis of psoriatic arthritis (PsA). The latter is currently indicated as a T-cell-mediated disease that is based on the activation of cellular immunity, followed by the hyperproduction and imbalance of key pro- A nd anti-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1â (IL-1â), IL-6, IL-12/23, and IL-17. The paper presents the basic principles of diagnosis and clinical manifestations of the disease and notes the importance of screening questionnaires, the use of which allows specialists to diagnose PsA early, by actively identifying articular complaints, the characteristic clinical and radiological signs of damage to the joint, spine, and entheses. It is pointed out that the key target of pharmacotherapy for PsA is to achieve remission or minimal activity of the main clinical manifestations of the disease, to slow down or prevent its radiographic progression, to increase the length and quality of life in patients, and to reduce the risk of comorbidities. The authors characterize the major groups of used drugs: Nonsteroidal anti-inflammatory drugs, conventional and targeted synthetic disease-modifying antirheumatic drugs, and biological drugs (inhibitors of TNF-α, IL-12/23, and IL-17). The key Treat-to-target principles of patient management are considered; it is noted that strict control over disease activity and treatment results provides suppression of all major clinical manifestations of PsA. The paper also shows the basic principles of the creation and further development of the All-Russian Registry of PsA patients, which makes it possible to optimize management decision-making on the provision of high-tech medical care and drugs for this cohort of patients.

© 2018 Ima-Press Publishing House. All rights reserved.  The clinical efficacy and safety of interleukin-6 (IL-6) receptor blockade have been well studied, but the data on the impact of therapeutic inhibition of IL-6 on B cells are scarce and contradictory. Preliminary reports have shown that B cell function and a humoral immune response may be modulated by an IL-6 receptor inhibitor. Objective: to assess the effect of 12-month tocilizumab (TCZ) therapy on B-cell phenotype and gene expression in RA and to analyze the association between B-cell subsets and RA activity. Subjects and methods. Examinations were made in 24 active RA patients (20 women and 4 men) (median age, 55 [49; 64] years; disease duration, 72 [24; 108] months; DAS28 5.8 [5.3; 6.3]; the patients were seropositive for rheumatoid factor (RF) (100%) and for anti-cyclic citrullinated peptide antibodies (87.3%). The patients received TCZ 8 mg/kg every 4 weeks. After 12 months of therapy, 54% of patients were categorized as good responders, 46% as moderate responders according to the EULAR response criteria. A control group consisted of 29 volunteers (21 women and 8 men; median age, 58.5 [53.0; 62.0] years). Peripheral blood lymphocytes were immunophenotyped at the time of enrollment and after 12 months. The absolute and relative counts of CD19+B lymphocytes, memory B cells (CD19+CD27+), non-switched memory B cells (CD19+IgD+CD27+), switched memory B cells (CD19+IgDCD27+), naive (CD19+IgD+CD27-), double-negative (CD19+IgD-CD27-), transitional (CD19+IgD+CD10+CD38++CD27) B cells, plasma cells (CD19+CD38+), and plasmablasts (CD19+CD38+++IgD-CD27+CD20-) were estimated using multicolor flow cytometry. Results and discussion. The relative and absolute counts of memory B cells (CD19+CD27+) (1.3 [0.9; 1.7]%, 0015 [0.001; 0.003]•10 9 /l), switched memory B cells (CD19+IgD-CD27+) (6.8 [3.6; 11.6]%, 0.01 [0.005; 0.02]•10 9 /l), and the absolute number of transitional B cells (CD19+CD38++CD10+IgD+CD27-) (0.00009 [0; 0.00028]•10 9 /l) were found to be lower in RA patients than in donors: 2.2 [1.1; 3.0]%, 0.003 [0.001; 0.007]•10 9 /l; 12.8 [9.3; 17.0]%, 0.02 [0.01; 0.04]•10 9 /l; 0.0001 [0; 0.0003]•10 9 /l, respectively (p<0.05 for all cases). After 12 months of TCZ therapy initiation, there were decreases in the relative and absolute counts of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) from 0.15 [0.1; 0.3] to 0.1 [0.01; 0.1]% and from 0.0003 [0.00007; 0.004]•10 9 /l to 0.0001 [0; 0.0003]•10 9 /l, respectively (p<0.05). At the same time, the relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) remained lower in RA patients than in donors: 1.0 [0.7; 1.2] and 2.2 [1.1; 3.0]%; 0.001 [0.006; 0.003]•10 9 /l and 0.003 [0.001; 0.007]•10 9 /l; 3.1 [1.1; 4.2] and 12.8 [9.3; 17.0]%; 0.003 [0.002; 0.006]•10 9 /l and 0.02 [0.01; 0.04]•10 9 /l, respectively (p<0.05 for all cases). Following 12 months of TCZ therapy, the numbers of other B-cell subpopulations were not considerably altered. When included in the study, the patients with RA showed correlations between the absolute count of memory B cells (CD19+CD27+) and the level of C-reactive protein (r=0.50; p<0.05); between the absolute count of plasmablasts (CD19+CD38+++CD27+IgD-CD20-) and the level of RF (r=0.41 and r=0.52; p<0.05). There were no correlations of B cell subsets with clinical and laboratory findings after 12 months of TCZ initiation. Conclusion. Immunophenotyping of peripheral blood B lymphocyte subsets showed the lower relative and absolute counts of memory B cells (CD19+CD27+) and switched memory B cells (CD19+CD27+IgD-) in RA patients than in healthy donors. The found correlations between the counts of memory B cells and plasmablasts and the values of laboratory parameters in patients with high RA activity may suggest that B lymphocytes are involved in the pathogenesis of RA. There was a decline in plasmablast levels after 12 months of TCZ therapy.

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to determine risk factors (RFs) for venous thromboembolic events (VTE) in patients with rheumatoid arthritis (RA). Subjects and methods: The investigation enrolled 374 patients (311 women and 63 men) with a reliable diagnosis of RA who met the 2010 ACR/EULAR classification criteria. The patients' mean age was 53.7±13.6 years; the disease duration was 12.1±10.7 years. All the patients were treated at the V.A. Nasonova Research Institute of Rheumatology Clinic during the period from 2014 to 2017. A standard clinical examination of the peripheral joints was performed. RA activity was measured using DAS28. A survey was made using a questionnaire including questions on traditional RFs for VTE and RFs that might be caused by RA and its therapy. Results and discussion. VTE were recorded in 45 (12%) out of the 374 patients. Group 1 included 45 patients with VTE; Group 2 consisted of 329 patients without VTE. Multidimensional analysis showed an increased risk of developing VTE in RA under the influence of the following factors: high inflammatory activity; lower extremity varicose veins; hypercholesterolemia; and hypertension. Their weighted coefficients were 1.1, 2.5, 1.0, and 0.9, respectively. According to the obtained model (p<0.001), the risk of VTE in RA can be predicted by the following formula: Z = 1.1 • high RA activity (Yes = 1/No = 0) + 2.5 • lower extremity varicose veins (Yes = 1/No = 0) + + 1.0 • hypercholesterolemia (Yes = 1/No = 0) + 0.9 • hypertension (Yes = 1 / No = 0). Conclusion: The increased risk for VTE in RA patients determines the need for its timely assessment, by taking into account the known risk factors as both standard ones and those caused by the disease itself and its therapy. This risk assessment is necessary for the timely adequate treatment and prevention of thrombotic events in RA.

© 2018 Ima-Press Publishing House. All rights reserved. Objective: to evaluate the clinical efficacy of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval in patients with active rheumatoid arthritis (RA) 12 and 24 weeks after initiation of treatment. Subjects and methods. Examinations were made in 20 active seropositive RA patients who had not been previously treated with biological agents (BAs), but received two infusions of the rituximab biosimilar Acellbia® at a dose of 600 mg intravenously at a 2-week interval during stable therapy with methotrexate (MT) and glucocorticoids (GCs). The European League Against Rheumatism (EULAR) response criteria (Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI), and Simplified Disease Activity Index) and the American College of Rheumatology (ACR) criteria were used to evaluate the efficiency of Acellbia® therapy. Disease remission was identified by DAS28 and 2011 ACR/EULAR criteria. The safety profile (the frequency of all reported adverse events) corresponds to the data on the safety of rituximab (MabThera®). Results and discussion. At the time of inclusion, median DAS28 was 5.6 [4.9; 6.8], SDAI - 27.1 [23.0; 39.9], and CDAI - 26.6 [22.2; 37.0]. At week 12 after initiation of Acellbia® therapy, they decreased to 4.2 [3.24; 4.75], 14.4 [8.5; 20.7], and 13.2 [7.9; 19.0] respectively, which remained at 24-week follow-up (p<0.01). At week 12, the frequencies of ACR 20%, 50%, 70% improvements were 70, 55, and 5%; at week 24, these were 75, 45, and 15%, respectively. A good or moderate EULAR response at week 24 was observed in 25 and 60% of patients, respectively. At week 24, DAS28, SDAI, and CDAI remissions were achieved by 4 (20%), 2 (10%), and 1 (5%); low disease activity - by 4 (20%), 5 (25%), and 6 (30%) patients, respectively; high disease activity as measured by SDAI and CDAI remained in 3 (15%) patients. Two patients (10%) met the 2011 ACR/EULAR remission criteria at 24 weeks. Conclusion. The rituximab biosimilar Acellbia® 600 mg used in patients with active seropositive RA is clinically effective and comparable in the safety profile as shown in investigations of the brand-name MabThera® (F. Hoffman-La Roche Ltd., Switzerland) at a low dose (500 mg), as well as the first BA.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. Tumour necrosis factor alpha inhibitors are widely used in the treatment of juvenile idiopathic arthritis (JIA). To achieve maximum efficiency of genetically engineered biologic drugs, it is necessary to study predictors of the response to therapy. Objective. Our aim was to identify early predictors of the response to adalimumab therapy in patients with JIA without systemic manifestations. Methods. A prospective cohort study analysed treatment results of patients with JIA without systemic manifestations, who were prescribed adalimumab for the period from August 2008 to August 2014. We studied the relationship between baseline demographic indicators as well as baseline and registered after one month of treatment clinical and laboratory parameters and the best (remission according to the Wallace criteria) response to therapy after one year. Results. In the first year of therapy, 94 (43.9%) of 214 patients achieved remission according to the Wallace criteria. In a multivariate analysis, predictors of achieving remission after one year of adalimumab therapy were the improvement according to the ACR70 criterion after one month of therapy [odds ratio (OR) 3.3; 95% confidence interval (CI) 1.7-6.7], a history of uveitis (OR 1.86; 95% CI 1.03-3.33), a decrease in the number of joints with active arthritis after one month of therapy (OR 1.09; 95% CI 1.02-1.16). During therapy, injection reactions in the form of pain were observed in 36 (16.8%) of 214 patients, infectious diseases of ENT organs - in 85 (39.7%), of the respiratory tract - in 17 (7.9%), and tubinfection - in 13 (6.1%) children. Conclusion. The presence of uveitis, rapid reduction in the number of joints with active arthritis and a high level of response to treatment after one month of adalimumab therapy are predictors for achieving remission during the first year of treatment.

© 2018 Ima-Press Publishing House.All right reserved. Objective: to study changes of acute-phase reactants (erythrocyte sedimentation rate – ESR, C-reactive protein – CRP), autoantibodies (IgM/IgA rheumatoid factors – RF, anti-citrullinated protein antibodies), immunoglobulin classes G, M, and A, and CD19+ B-lymphocytes in patients with rheumatoid arthritis (RA) 12 and 24 weeks after initiation of therapy with a rituximab (RTM) biosimilar at a total dose of 1200 mg. Subjects and methods. Examinations were made in 20 patients with a reliable diagnosis of RA (including 18 women; median age, 61.5 [54; 66.5] years; disease duration, 39.5 [20; 84] years; DAS28, 5.6 [4.9; 6.8]). All the patients received two intravenous infusions of RTM (Acellbia®) 600 mg at a 2-week interval during therapy with methotrexate, nonsteroidal anti-inflammatory drugs, and glucocorticoids. Clinical and laboratory parameters were analyzed immediately before therapy and then 12 and 24 weeks after the first infusion of the drug. Results and discussion. DAS28, ESR, and CRP level in respondents significantly decreased 12 and 24 weeks after RTM administration. The serum IgM RF concentration in the respondents was found to be significantly reduced at weeks 12 and 24 and amounted to 79.7 and 87.1% of baseline, respectively. The IgA RF level significantly decreased by 72 and 85% of baseline at weeks 12 and 24 of RTM therapy, respectively, in patients with a good response, and by 59.7 and 67.5% at weeks 12 and 24 in patients with a satisfactory response. The serum concentration of anti-cyclic citrullinated peptide antibodies in the respondents remained high throughout the follow-up. All the patients achieved CD19+ B-cell depletion at week 12 of therapy (absolute levels, 0); there was an increase in the level of CD19+ B-lymphocytes at week 24 (0.0030 [0.0003; 0.0270] 109/l). In both in the good and satisfactory response groups, the mean immunoglobulin levels remained within normal limits. Conclusion. The analysis of the efficiency of two infusions of the RTM biosimilar at a total dose of 1200 mg following 24 weeks of therapy initiation suggests that the drug is able to cause reductions in disease activity, laboratory signs of inflammatory activity, autoantibody concentrations, and complete B-lymphocyte depletion.

© 2018 Ima-Press Publishing House.All right reserved. Impaired B-cell immunological tolerance plays a central role in the pathogenesis of autoimmune rheumatic diseases and autoimmune diseases of another nature. B-cells link innate and acquired immunity: they express Toll-like receptors that respond to danger signals; act as antigen-presenting cells; induce an antigen-specific immune response; determine the development of immunological memory; and synthesize a wide range of cytokines that regulate (stimulate or suppress) an immune response and inflammation. In autoimmune diseases, there are metabolic and B-cellular signaling disturbances that lead to defects in B-regulatory, T-regulatory, follicular T-helper, and dendritic cells. B-cells synthesize organ-nonspecific and organ-specific autoantibodies that are biomarkers for autoimmune diseases and play an important role in their immunopathogenesis. Anti-B-cell therapy that causes B-cell depletion in blood and target organs is effective in a wide range of autoimmune diseases. Its efficiency is determined by various mechanisms, such as suppression of pathogenic autoantibody synthesis; modulation of the function of B-cells (antigen presentation, cytokine synthesis, and costimulation), T-lymphocytes and dendritic cells. Further study of a strategy for targeted anti-B-cell therapy, mechanisms of action, and new targets is important for the progress of modern rheumatology to improve the treatment strategy of autoimmune rheumatic diseases.

© 2018 Ima-Press Publishing House. All right reserved. In accordance with international and Russian guidelines for the management of patients with rheumatoid arthritis (RA), after its diagnosis, a synthetic disease-modifying antirheumatic drug is prescribed, among these drugs, methotrexate is anchor and, when the latter is impossible to use, leflunomide is commonly administered. Objective: to evaluate the efficacy and safety of a leflunomide generic (Elafra) during a multicenter follow-up. Subjects and methods. The investigation enrolled 347 patients aged over 18 years who met the 2010 ACR/EULAR criteria for RA, had its duration of less and more than 2 years, signed informed consent, and followed up in 29 centers of Russia. Elafra was prescribed at a saturating dose of 100 mg for the first 3 days, then 20 mg/day. There might be a temporary two-fold reduction in the dose when adverse events (AE) occurred. The patients were examined before and 4, 12 and 24 weeks after beginning leflunomide treatment. The treatment efficiency was evaluated with DAS28 and CDAI and by the physician global assessment. Results and discussion. The patients were divided into two groups: 1) 125 patients with RA of less than 2 years' duration and 2) 222 patients with RA of more than 2 years' duration. The mean age of patients in Group 1 was 48.7±12.9 years; that in Group 2 was 52.5±11.95 years; the mean disease duration was 11.9±7.8 and 90.99±54.28 months, respectively. During 24-week treatment, there was a highly significant decrease in all assessed clinical, laboratory parameters and indices of RA activity in both groups. At 4 weeks of treatment, the effect was observed in 91.8% of the patients in Group 1 and in 84.6% in Group 2, whereas at 12 weeks the effect was noted in almost all patients (99.1% and 96.9% in Groups 1 and 2, respectively). The highest rate of AE during Elafra therapy was recorded in the early periods: at 4 weeks, AE were noted in 6.5% of the patients in Group 1 and in 9.9% in Group 2, without needing to discontinue the drug. Treatment continuation decreased the rate of AE. Because of its intolerance, Elafra was discontinued due to in one case in Group 1 (diarrhea at 24 weeks of treatment) and in 6 cases in Group 2 (at 12 and 24 weeks of treatment). Conclusion. Treatment with leflunomide (Elafra) leads to the rapid development of its effect in early and late RA in most patients and is characterized by a good tolerability.

© 2018 Publishing House of the Union of Pediatricians. All rights reserved. Background. To assign genetically engineered biologic drugs, we need data on the predictors for response to therapy. Prognostic factors for the response to tocilizumab in patients with juvenile idiopathic arthritis (JIA) without systemic symptoms are poorly studied. Objective. Our aim was to reveal early predictors for the response to tocilizumab therapy in patients with JIA without systemic symptoms. Methods. A retrospective cohort study enrolled patients with JIA without systemic symptoms who received tocilizumab therapy between July 2009 and August 2017. We assessed the association between the initial demographic, clinical, and laboratory parameters in patients and the best response (according to the ACR90 criteria) to treatment after a year. Results. The study included 95 (girls 85%) patients; the mean age was 10.3 (6.0; 13.6). During the first year of therapy, 71 (75%), 55 (58%), 38 (40%), and 22 (23%) patients achieved the improvement according to ACR30/50/70/90 criteria, respectively; 22 (23%) patients reached disease inactive stage according to the Wallace criteria. When performing multivariate analysis, the following improvement predictors were revealed based on the ACR90 criteria after a year of treatment: decrease in serum C-reactive protein level during the first month of therapy [odds ratio (OR) 1.024; 95% confidence interval (CI) 1.007-1.051], decrease in disease activity score on the visual analogue scale according to the parent/patient assessment (OR 1.048; 95% CI 1.005-1.105), early onset of the disease (OR 0.38; 95% CI 0.16-0.72), persistent oligoarthritis according to the ILAR (OR 9.9; 95% CI 1.5-109.3). During the first year of tocilizumab administration, neutropenia was registered in one patient, leukopenia - in three cases, and urticaria - in one case. Conclusion. The variant of JIA, the age at the disease onset, and the disease course pattern in the first month of tocilizumab therapy are the predictors of treatment efficacy throughout the year.

© 2018 Ima-Press Publishing House. All rights reserved. Rheumatoid arthritis (RA) is an immunoinflammatory (autoimmune) rheumatic disease of unknown etiology, which is characterized by chronic erosive arthritis and systemic visceral organ damage that results in early disability and shorter patient survival. Despite RA treatment advances associated with the design of novel drugs and the improvement of treatment strategies to achieve remission in many patients, there are still many theoretical and clinical problems concerning both the definition of the concept of remission, its characteristics and types and approaches to the optimum policy of symptomatic and pathogenetic drug therapy at different stages of the disease, the use of which will be able to rapidly induce and maintain remission in the long-term. Further investigations are needed to study the nature of heterogeneity of pathogenetic mechanisms of RA and approaches to early diagnosis, to improve methods for monitoring disease activity and biomarkers for the efficiency of and resistance to therapy and, finally, to develop differentiation therapy, including those related to a search for new therapeutic targets.

© 2018 Ima-Press Publishing House. All rights reserved. Rheumatoid arthritis (RA) and the use of glucocorticoids (GCs) are proven risk factors for osteoporosis (OP) and osteoporotic fractures (OPF). There are also other reasons for increased fracture risk in RA. Objective: to determine the rate of RA in an epidemiological sample of persons aged 50 years and older and to identify those in need of antiosteoporotic therapy among the patients with RA in order to prevent OPF. Subjects and methods. The epidemiological sample included 18,018 people aged 50 years and older (13,941 women and 4,077 men; mean age, 62±10 years). The survey consisted of a unified questionnaire, measurement of daily dietary calcium intake, and calculation of a 10-year fracture risk using the FRAX® algorithm. Results and discussion. The prevalence of RA in the epidemiological population sample aged 50 years and older was 1.7% (1.9% in women and 1.2% in men; p=0.0047). The mean FRAX® values for major OPF in RA patients were significantly higher than those in non-RA individuals: 18.4±10 and 13.2±7.9%, respectively (p=0.0001) for women and 8.9±6.4 and 6.2±3.7%, respectively (p=0.0001) for men. 42% of the patients with RA were at high risk for OPF. Thus, 48% of the women with RA had FRAX® values above the therapeutic intervention threshold; and the non-RA group needed antiosteoporotic therapy significantly less (31%; p=0.00001). At the same time, the detection rate of high-risk OPF in men with and without RA did not differ significantly (8 and 5%, respectively; p>0.05). The most common risk factors (RFs) for OP and OPF in RA patients included previous fractures (33%), secondary causes of OP (30%), GC use (18%), and, additionally, smoking (33%) in male patients with RA. The female patients with RA significantly more frequently took GCs (17%) and had other secondary causes of OP and OPF (33%) than those without RA (7.7% (p=0.0001) and 23% (p=0.0004, respectively). The male patients with RA versus to the population-based control showed significant differences when they only used GCs (20 and 5%, respectively; p = 0.0001); the remaining RFs were encountered at the same frequency. Less than half of the normal daily calcium intake was observed in 20% of men and 16% of women (p=0.53). Conclusion. 42% of the RA patients aged 50 years and older were at high risk for OPF and needed antiosteoporotic therapy. Every third woman with RA had at least one other comorbidity or condition associated with the increased risk of OPF. In the male patients with RA, the FRAX® algorithm could reveal only 8% of persons at high risk for fractures, while 58% of them had two or more additional RFs that can negatively affect bone mineral density and increase the risk of fracture. To identify those who require prevention and treatment of OP and OPF, it is preferable to perform bone densitometry of the axial skeleton among male patients with RA.