The paper gives the recommendations for the assessment of disease activity and functional status in patients with ankylosing spondylitis in clinical practice, which have been developed by experts, by taking into account international and Russian experience in managing these patients.

The Russian biotechnological company «BIOCAD» has designed a chimeric monoclonal antibody against CD20 (BCD-020, Acellbia®) that is a biosimilar of rituximab (RTM; MabThera®, F. Hoffmann-La Roche Ltd., Switzerland). In recent years, there has been evidence that RTM can be used at lower doses than those given in the standard recommendations and instructions for the use of this drug. This serves as the basis for the BCD-020-4/ALTERRA (ALTErnative Rituximab regimen in Rheumatoid Arthritis) trial, the objective of which was to investigate the efficiency and safety of using Acellbia® (at a dose of 600 mg twice at a 2-week interval) as the first biological agent (BA) for methotrexate (MTX)-resistant active rheumatoid arthritis (RA). The investigation enrolled 159 patients aged 18 to 80 years with active RA. After 24 weeks 65.7 and 29.4% of patients achieved 20% improvement by the American College of Rheumatology (ACR) criteria in the Acellbia® + MTX and placebo (PL) + MTX groups, respectively (p<0.0001). The differences in the ACR20 response rate in the two groups were 36.3% (95% CI, 19.27–53.28%). There were significant differences between the groups in the ACR50 response rates: 28.4% and 5.9% (p=0.001) and in the ACR70 ones: 12.8% and only 2.0%, respectively (p=0.036). Analysis of all recorded adverse events (AE) frequency showed no significant differences between the patients in the study and control groups and demonstrates its equivalence with that of RTM (MabThera®); all the AE were expectable. It is noted that antibodies to RTM with binding and neutralizing activities had no impact on the efficiency and safety of therapy.

Objective: to analyze the impact of methotrexate (MTX) therapy on percentage and absolute content of FoxP3+ regulatory T lymphocytes (Treg) in the peripheral blood of patients with early rheumatoid arthritis (RA) who had not previously received MTX.

Subjects and methods. The investigation included 45 patients with early RA (2010 ACR/EULAR criteria) who had not previously received MTX, including 39 women; median age was 52.0 [32.5; 57.5] years; disease duration, 5 [4; 6] months, DAS28, 5.01 [4.18; 5.8]; 71.1% of the patients were positive for rheumatoid factor and 88.9% – for anticyclic citrullinated peptide antibodies. As the first disease-modifying antirheumatic drug, all the patients were assigned to receive subcutaneous MTX at an initial dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. The percentage and absolute count of Treg (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; and FoxP3+CD274+) were measured by immunofluorescence staining and multicolor flow cytometry.

Results and discussion. At 24 weeks after starting the therapy, median DAS28, SDAI, and CDAI were 3.1 [2.7; 3.62], 7.4 [4.2; 11.4], and 7.0 [4.0; 11.0], respectively; DAS28 and SDAI remission/low disease activity was reached by 22 (56.4%) and 25 (64.1%) patients, respectively; 4 (10.3%) patients had no MTX treatment effect according to the EULAR criteria. After a 6-month course of MTX therapy, the whole group had increases in the percentage of CD4+cells (from 45.0 [38.0; 49.2] to 46.8 [39.9; 53.2]%) and in the percentage and absolute number of CD152+surface from 0.65 [0.22; 1.67] to 2.07 [1.11; 3.81]% and from 0.0002 [0.0001; 0.0008]•109 to 0.0007 [0.0004; 0.002]•109, and a moderate decrease in the percentage and absolute content of FoxP3+ICOS+ cells from 5.3 [2.1; 11.3] to 4.07 [1.6;6.6]% and from 0.002 [0.001-0.006]•109 to 0.0015 [0.0006-0.003]•109 (p<0.05 in all cases).

Conclusion. The use of MTX in early RA is accompanied by an increase in the proportion and number of Treg with a high level of activation markers, which may indicate their enhanced suppressor activity that is more pronounced among the patients who have achieved remission/low disease activity during the treatment.

Objective: to estimate changes in the cytokine profile in patients receiving abatacept (ABC).

Subjects and methods. The investigation enrolled 44 patients with rheumatoid arthritis (RA) who had been unsuccessfully treated with disease-modifying antirheumatic drugs and biological agents. A control group included 16 healthy donors. The majority of patients were women who were positive for rheumatoid factor (RF) (80%) and antibodies to cyclic citrullinated peptide (ACCP) (79.5%); the mean age was 49.6±13.9 years; the median disease duration was 2 [1.4; 3] years with high RA activity (mean DAS28, 5.2±0.8). The serum concentrations of interleukin (IL) 1β, IL-6, IL-17AF, tumor necrosis factor-α (TNF-α), VEGF-A, IP-10, and YKL-40 were measured by enzyme immunoassay before and 6 months after ABC therapy. Disease activity was assessed using DAS28 every 3 months. ABC was infused intravenously according to the standard regimen.

Results and discussion. The patients with RA as compared with the control group had significantly elevated levels of IL-6 (2.4 [1.1; 6.4] and 0.7 [0.62; 1.0] pg/ml; p=0.0002), YKL-40 (97 [68.4; 97.9] and 64 [52.4; 107.5] pg/ml; p=0.03), IP-10 (21 [12.9; 49.8] and 14 [9.2; 15.2] pg/ml, respectively; p=0.005). ABC caused a significant decrease in RA activity after 3 months of therapy (p<0.05). Following 6 months, 86% of the patients achieved good and moderate EULAR responses; low RA activity according to DAS28 was recorded in 52%. ABC induced significant decreases in the concentrations of IL-6 to 1.29 [0.9; 2.2] pg/ml (p=0.0006) and IP-10 to 14 [7.5; 28] pg/ml (p=0.007) after 6 months of therapy. A similar trend was observed when assessing changes in the concentration of matrix metalloproteinase 3 (MMP-3), which reduced from 30.1 [13; 82] to 10 [7.4; 55] pg/ml (p=0.0003), and in that of RF, which declined from 218 [9.6; 187] to 159 [9.7; 155] pg/ml (p=0.02). The lower levels of IL-6 (r=0.5) and IP-10 (r=0.32) significantly correlated with a decrease in DAS28 (p<0.05). There was a trend towards a more pronounced reduction in disease activity in patients positive for ACCP and antibodies to modified citrullinated vimentine (AMCV). The percentage of non-responders to therapy in the ACCP- and AMCV-negative groups was nearly twice as high as in those who were positive for these antibodies (27.2 and 16%; 26.7 and 14.8%, respectively), but these differences failed to reach significance. However, after 6-month of follow-up, the percentage of non-respondents in the AMCV-negative group was significantly higher than in the AMCV-positive group (20% and 0%, respectively; p=0.03). The patients who did not respond to ABC therapy had higher baseline levels of IL-6 (p=0.03) and YKL-40 (p=0.02).

Conclusion. ABC therapy results in a substantial reduction in the concentration of the proinflammatory cytokines IL-6 and IP-10, as well as MMP-3 and RF. The lower levels of IL-6 and IP-10 significantly correlated with a decrease in RA activity. There was a tendency towards a more pronounced reduction of disease activity in ACCP- and AMCV-positive patients. The high baseline levels of IL-6 and YKL-40 and the absence of AMCV may suggest that ABC therapy can be ineffective.

Objective: to determine the level of the N-terminal fragment of brain natriuretic peptide progenitor (NT-proBNP) in patients with systemic lupus erythematous (SLE) prior to immunosuppressive therapy and its possible association with inflammatory markers, traditional risk factors (TRFs) for cardiovascular diseases (CVD), and transthoracic echocardiographic (EchoCG) parameters.

Subjects and methods. The investigation enrolled 28 SLE patients fulfilled the 1997 ACR criteria, including 23 (82%) women (median age, 28.5 [25.0; 32.0] years), who had no clinical signs of CVD and received no immunosuppressive therapy. A control group consisted of 27 age-and sex-matched healthy donors. Disease activity was assessed by SLEDAI-2K; irreversible damages were measured using SLICC. The median duration of SLE was 21.0 [5.0; 60.0] months, the scores of SLEDAI-2K and SLICC/DI were 11 [8; 19] and 0 [0; 0], respectively. The investigators estimated the concentration of Creactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), carried out EchoCG, and assessed TRFs. The serum concentration of NT-proBNP was determined by electrochemiluminescence (Roche Diagnostics, Switzerland). The normal range for NT-proBNP was ≤125.0 pg/ml.

Results and discussion. The patients with SLE had elevated levels of NT-proBNP compared with the controls: 160.7 [88.6; 335.4] and 55.2 [36.6; 70.3] pg/ml, respectively (p < 0.001). The patients were divided into two groups: 1) 18 (64%) patients had a NT-proBNP concentration of > 125.0 pg/ml; 2) 10 (36%) patients had no more than this level. As compared with Group 2, Group 1 had the elevated values of IgG anti-cardiolipin (aCL) antibodies (p < 0.01), creatinine (p < 0.05), left ventricular (LV) end-systolic dimension (ESD) (p < 0.05) and decreases in LV ejection fraction (EF) (p < 0.01), glomerular filtration rate (GFR) (p < 0.05), and concentration of anti-Ro antibodies (p < 0.05). In all the patients (n = 5 (18%)) with LV diastolic dysfunction (DD), the NT-proBNP level was much higher than normal; its median was 799.2 [276.6; 1777.0] pg/ml, but no statistically significant differences were found in the frequency of LV DD between the groups (p = 0.066). In the patients with SLE, the NT-proBNP level correlated positively with that of creatinine (r = 0.480; p < 0.01), uric acid (r = 0.427; p < 0.05), IgG aCL (r = 0.710; p < 0.001), anti-double-stranded DNA (anti-dsDNA) antibodies (r = 0.395; p < 0.05), antinuclear antibodies (ANA) (r = 0.256; p < 0.05), LV ESD (r = 0.442; p < 0.05), pulmonary artery systolic pressure (r = 0.486; p < 0.05) and negatively with hemoglobin level (r = -0.493; p < 0.01), C4 complement component (r = -0.475; p < 0.05), GFR (r = -0.58; p < 0.01), and EF (r = -0.505; p < 0.01). The level of NT-proBNP was ascertained to be unassociated with the clinical manifestations of SLE (skin, mucosae, kidneys, nervous system damage, as well as arthritis, serositis, and hematological disorders) and markers of inflammation (CRP, IL-6, TNF-α).

Conclusion. The NT-proBNP concentration in the patients with SLE was significantly higher than in the control group (p < 0.001), more than 60% of the untreated SLE patients had elevated NT-proBNP values (>125.0 pg/ml). The higher level of NT-proBNP is associated with the immunological parameters of SLE activity (elevated values of IgG aCL, anti-dsDNA, and ANA as well as C4 hypocomplementemia) and with the markers that reflect deterioration in renal and myocardial functions. There was no relationship of NT-proBNP levels to the clinical manifestations of SLE and the markers of inflammation (CRP, IL-6, and TNF-α) and TRFs.

Increased arterial stiffness is one of the additional risk factors (RFs) for cardiovascular diseases along with traditional RFs, such as male gender, age, dyslipidemia, hypertension, and smoking. In rheumatoid arthritis (RA), the risk of cardiovascular events, including coronary heart disease (CHD), is significantly higher than that in the general population, which may be associated with the characteristics of the underlying disease or the prevalence of traditional RFs.

Subjects and methods. The results of investigating the arterial stiffness in 56 patients including 46 with RA and 10 with CHD without inflammatory joint disease (a control group) were analyzed. Arterial stiffness was assessed by carotidfemoral pulse wave velocity (cfPWV) in the area from the carotid artery to the femoral one, which was determined by applanation tonometry, as well as by CAVI that was calculated according to the data of volume sphygmography.

Results and discussion. According to the investigation encompassing exercise tests and coronary angiography, the group of patients with RA was divided into two subgroups, depending on the presence or absence of coronary artery disease caused by atherosclerosis. The patients' age was 38 to 77 years (mean age 60.3±7.2 years); the male proportion was 34.8%.

Conclusion. The presence of RA with and without CHD is associated with a significant rise in arterial stiffness compared to isolated CHD (cfPWV, 13.6 and 8.6 m/sec, respectively). The increase in cfPWV and CAVI compared with the age norm was revealed in the majority of RA patients both with and without CHD.

Objective: to carry out linguistic and cultural adaptation and validation of the Kujala questionnaire that is today one of the most popular orthopedic tools used to evaluate the severity of pain in the anterior part of knee joint.

Subjects and methods. In accordance with protocols on this type of investigations, the questionnaire was first translated directly and then back. Furthermore, an intermediate Russian-language version of the Kujala questionnaire was tested in 15 patients, followed by error correction and approval of its final Russian-language version. A study group included 50 patients who complained of obvious pain in the anterior part of knee joint and answered the questionnaire twice (for its test-retest reliability) every two or three days.

Results and discussion. The intraclass correlation coefficient (ICC) equal to 0.948 (95% confidence interval, 0.025–0.967) indicated a high test-retest reliability of the Russian-language version of the Kujala questionnaire. Cronbach's alpha coefficient of 0.956 corresponded to a high level of internal consistency, which also suggested that the proposed version of the questionnaire had a high reliability. The criterion-related validity assessment, by calculating the Spearman correlation coefficient between the results of primary and repeated surveys using the Russian-language version of the Kujala questionnaire, as well as between the Russian- language versions of the Kujala questionnaire and the SF-36, showed their high correlation.

Conclusion. The findings indicate that the Russian-language version of the Kujala questionnaire is a valid and reliable tool for subjective assessment of the severity of pain in the anterior part of knee joint.

Mental disorders (MDs) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) are characteristic of the majority of patients with rheumatoid arthritis (RA); however, the effects of disease-modifying antirheumatic drugs (DMARDs), biological agents (BAs), and their combinations with psychopharmacological drugs (PPDs) on these abnormalities have been insufficiently studied.

Objective: to investigate trends in the incidence of MDs in RA patients receiving different treatment regimens.

Subjects and methods. The investigation included 128 RA patients (13% men and 87% women) who fulfilled the 1987 American College of Rheumatology criteria; their mean age was 47.4±0.9 years; the median duration of RA was 96 [48; 228] months. RA activity was found to be high, moderate, and low in 48, 56, and 24 patients, respectively. DAS28 averaged 5.34±0.17. 80% of the patients received DMARDs. MDs were diagnosed based on ICD-10 coding, by using a semi-structured interview and scales, such as the Hospital Anxiety and Depression Scale, the Hamilton Anxiety Scale, and the Montgomery-Asberg Depression Rating Scale. Clinical and psychological procedures were used to diagnose CI. At the study inclusion stage, ADS disorders were detected in 123 (96.1%) patients; CI was found in 88 (68.7%). Forty-one (32.1%) patients were diagnosed with major depression (an obvious or moderate depressive episode), 53 (41.4%) patients had minor depression (a mild depressive episode and dysthymia), and 29 (22.6%) had anxiety disorders (ADs) (adjustment disorders with anxiety symptoms, as well as generalized anxiety disorder). The dynamics of MDs was estimated in 112 (87.5%) of the 128 patients and in 83 (64.8%) at one- and five-year follow-ups, respectively. The following groups were identified according to the performed therapy: 1) synthetic DMARDs (n = 39); 2) synthetic DMARDs + PPDs (n = 43); 3) BAs + DMARDs (n = 32); 4) BAs + DMARDs + PPDs (n = 9).

Results and discussion. In Group 1, the frequency of major depression increased insignificantly from 25% to 32.2 and 33.3% (p = 0.36) at one- and five-year follow-ups, respectively; that of minor depression decreased from 51% to 48.4 (p = 0.5) and 50% (p = 0.6) respectively; the number of patients with ADs declined significantly from 24% to 3.2 (p = 0.018) and 4.2% (p = 0.021), respectively. The frequency of CI rose from 63.5% to 64.5 and 81.8%, respectively (p = 0.12). In Group 2, the frequency of major depression decreased from 43 to 19% (p = 0.049) at one-year follow-up; and none of the patients was found to have ADS disorders at five-year follow-up (p < 0.001); the frequency of minor depression dropped from 38% to 23.8 and 7.1% at one-year (p = 0.35) and five-year (p = 0.002) follow-ups, respectively; the frequency of ADs fell from 19% to 4.8 (p = 0.044) and 0% (p = 0.012), respectively. The frequency of CI decreased insignificantly from 80.9% to 76.2 (p = 0.39) and 61.5% (p = 0.061), respectively. In Group 3 treated with BAs, the frequency of major depression increased statistically insignificantly from 31.2% to 37.9 (p = 0.39) and 42.8% (p = 0.28) at oneand five-year follow-ups, respectively; the frequency of minor depression rose insignificantly from 37.5% to 48.3 (p = 0.28) and 52.4% (p = 0.21), respectively; and that of ADs dropped from 25 to 0% at one-year (p = 0.003) and five-year (p = 0.011) follow-ups. Moreover, the frequency of CI increased from 75% up to 79.3 (p = 0.46) and 90% (p = 0.16) at one- and five-year follow-ups respectively. In Group 4, the frequency of major depression decreased significantly from 66.7 to 22.2% (p = 0.076) and complete regression (p = 0.004) at one- and five-year follow-ups, respectively; that of minor depression increased slightly from 11.1 to 33.3% (p = 0.28) due to the transformation of major depression into minor one at one- and five-year follow-ups, respectively; the frequency of ADs fell from 22.2% to zero at 5 years; and the incidence of CI declined 66.7 to 57.1% (p = 0.54).

Conclusion. Synthetic DMARDs had no effect on the ADS disorders and CI in patients with RA; BAs promoted the regression of ADs and did not affect the progression of depression and CI. A combination of DMARDs and BAs used at the adequate dose of PPDs for the same period led to the regression of ADS disorders and the reduction in the frequency of CI.

The program for the prevention of acute rheumatic fever (ARF) and recurrent attacks of the disease includes primary and secondary prevention. The basis for the primary prevention of ARF are activities aimed at increasing the level of the body’s innate immunity and adaptive responses to adverse environmental conditions, as well as the timely diagnosis and adequate antimicrobial therapy of group A streptococcus throat infections, such as sore throat and pharyngitis. Secondary prevention aims to prevent recurrent attacks and disease progression in individuals who have experienced ARF and provides regular twenty-four-hour administration of long-acting penicillin (benzathine benzylpenicillin)

Rheumatoid arthritis (RA) is a chronic immunoinflammatory (autoimmune) disease manifested by progressive joint destruction, systemic inflammation of the internal organs, and a wide range of comorbidities associated with chronic inflammation and frequently with adverse drug reactions. However, despite the major advances in the early diagnosis and treatment of RA, which have led to the radical improvement of prognosis in many patients, the problem of pharmacotherapy for RA is far from being solved. This is determined by a lack of sensitive and specific diagnostic and prognostic biomarkers in the early stage of the disease and, most importantly, by the heterogeneity of immunopathogenesis mechanisms in both at the onset of RA and during its progression, which make the personalization of therapy difficult in the patients. Selective block of inflammatory mediators with innovative medicines is frequently associated with primary inefficiency, secondary drug resistance, the development of generalized immunosuppression, the paradoxical activation of an autoimmune process, and the aggravation of comorbidities. At the same time, it is difficult to search for new RA pharmacotherapy targets since the nature of immunopathological disorders in patients can be substantially different from the inflammatory process that takes place when simulating arthritis in laboratory animals. The paper discusses the novel drugs that are used in rheumatology to treat RA or tested in different phases of preclinical or clinical trials, such as tumor necrosis factor-α inhibitors, interleukin-6 (IL-6), IL-17, anti-B cell therapy, bispecific antibodies, blockers of JAK (and other signaling molecules), bioelectronic vagus nerve activation, dendritic cell-based immunotherapy, and other therapies, as well as approaches to secondary prevention of RA in patients with undifferentiated arthritis and clinically suspect arthralgia, who are at high risk for RA. Decoding the mechanisms underlying the pathogenesis of RA and a chronic inflammatory process as a whole has created preconditions for the design of novel medications for the prevention and treatment of this disease, the introduction of which into clinical practice should lead to a radical improvement of prognosis in this disease.

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease characterized by chronic erosive arthritis (synovitis) and a systemic inflammatory lesion of the internal organs, which results in early disability and worse quality of life in patients. The accumulated data on the efficacy, safety, and cost-effectiveness of anti-B cell therapy allow identification of rituximab (RTM) as an extremely important drug of first- or second-line therapy with biological agents after ineffective treatment with tumor necrosis factor-α (TNF-α) inhibitors. In this connection, the choice of a personalized treatment regimen remains relevant in each specific case as before. Clinical experience with RTM suggests that the drug is highly effective in improving both clinical manifestations and quality of life in patients with active RA that is characterized by resistance to disease-modifying antirheumatic drugs and TNF-α inhibitors, as well as in those with early RA. The current literature presents a large amount of data on the role of prior therapy and the impact of the stage of RA when using different RTM doses on its efficiency, some of which will be discussed in this review.

Psoriasis (Ps) is a chronic systemic disease that affects the skin. Investigation could reveal the high prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with Ps compared with the general population, especially in those who have moderate to severe Ps with a high Ps area severity index (PASI). Similar pathogenic processes play a definite role in this relationship. The most likely causes are recognized to be insulin resistance and elevated levels of proinflammatory cytokines. According to recent evidence, the prevalence of NAFLD and metabolic syndrome in patients with Ps is higher than that in the general population. In addition, patients with NAFLD and Ps are at higher risk of severe liver fibrosis than those with NAFLD without Ps. Therapy for this condition certainly needs not only to modify traditional risk factors, but also to reliably suppress inflammation. Obesity and NAFLD have a negative impact on the results of treatment in patients with psoriatic arthritis with biological agents.

The paper reviews the most important works devoted to the study of the impact of individual foods and food components on the risk of gout, its clinical manifestations and the level of uricemia. It considers some mechanisms probably underlying the impact of dietary patterns on the level of uricemia. It is shown that the available data on possible alterations in the diet with their proper application can considerably affect both the incidence of gout and the course of the current disease.

The paper describes a case of infliximab-induced lupus-like syndrome in a female patient with rheumatoid arthritis and discusses the possible causes of this pathology.