The key element in the pathogenesis of systemic autoimmune rheumatic diseases is the breakdown of immunological tolerance and the formation of a pool of autoreactive cells. This leads to uncontrolled activation of the effector arm of cellular (T-lymphocytes) and humoral (B-lymphocytes and plasma cells) immunity, proliferation of autoreactive clones, and the formation and persistence of immunological memory cells. In this process, T-cells, B-cells, and plasma cells of immunological memory, in interaction with a complex of pathogenic signals from the microenvironment, ensure the stability and adaptability of the developing inflammatory process.

In modern clinical practice, the prevailing approach to prescribing medications is the "therapeutic pyramid" strategy, which involves gradual escalation of treatment until remission is achieved. This approach does not address the mechanisms of immunological tolerance and, as a result, requires lifelong therapy and is associated with numerous adverse effects.

The term “depletion-restitution therapy” is proposed (from English “depletion” – exhaustion; and Latin “restitutio ad integrum” – restoration to the original state, complete recovery) to describe an alternative approach. This approach is characterized by methods based on massive, shortterm cytotoxic impact, leading to profound reduction of pathogenic autoreactive cellular clones, followed by repopulation with "naive" cellular elements. Consequently, this restores tolerance mechanisms and enables the formation of ultra-long, drug-free remissions.

Currently, the principles of depletion-restitution therapy have already been integrated into oncology, hematology, and neurology. Among the most promising potential targets for such therapy in rheumatology are the effectors of the humoral immune system: B-cells, plasmablasts, and plasma cells. At the present stage, the most promising methods for implementing this approach are CAR-T cells and therapeutic bispecific monoclonal antibodies.

Primary systemic vasculitides are well-defined nosological entities, but several diseases can mimic their clinical, laboratory, radiological and histological features. The first part of the article provides an overview of the mimickers of large and medium vessel vasculitis, which include infections and non-genetic vasculopathies. It is extremely important to make a diagnosis before starting therapy in order to avoid severe and even catastrophic consequences when treating patients with these complex diseases.

During dynamic follow-up of patients with idiopathic inflammatory myopathy (IIM), changes in disease activity and damage caused are assessed using several generally recognized instruments. In parallel, objective methods of visualization are used, in particular magnetic resonance imaging (MRI) of the muscles. Currently, the relationship between the results of MRI and clinical and laboratory parameters in dynamics is not well studied.

Objective: to evaluate the main signs of muscle involvement using MRI in dynamics and to compare them with clinical and laboratory parameters, activity indices and damage in patients with IIM.

Material and methods. The study included 32 patients with diseases from the group of IIM that met the EULAR/ACR 2017 classification criteria. All patients underwent MRI of the hip and calf muscles twice on the Philips Multiva 1.5 Tesla (Philips, The Netherlands) employing T1, T2, and STIR-T2 sequences, signs of oedema and fatty remodeling were assessed on a 4-point semiquantitative scale. The median time between examinations was 15.5 [9; 24] months. A standard clinical examination, including a manual muscle test (MMT-8), was performed at the initial and the second examinations of the patients. Disease activity was determined using the MITAX index and irreversible changes were assessed using the MDI damage index.

Results and discussion. During follow-up a statistically significant decrease in total oedema score and an increase in total fatty remodeling score in the thighs and calves was observed (p<0.05). The decrease in oedema total score in the thighs was associated with an increase in muscle strength according to the results of the MMT-8 (p=0.03), a decrease in creatine phosphokinase level (CPK; p=0.005) and activity index (p=0.003). The increase in the total thigh fatty replacement score was associated with a decrease in muscle strength according to the MMT-8 (p=0.01) and an increase in irreversible muscle changes according to the damage index (p=0.002). A decrease in total calves oedema score was associated with a decrease in CPK level (p=0.002) and activity index (p<0.001). A change in the total calves fatty replacement score was not associated with statistically significant changes in clinical and laboratory parameters of the disease.

Conclusion. Changes in the main signs of muscle involvement, oedema and fatty replacement, according to MRI showed a clear parallelism with the dynamics of clinical and laboratory indicators, which confirms the sensitivity of this method to changes in both the activity and severity of the disease. Thus, MRI of muscles in patients with muscle weakness makes it possible to distinguish the signs of inflammation from the manifestations of irreversible damage, which is of great importance for determining treatment tactics and prognosis.

Antiphospholipid antibodies (aPL) are a sign of acquired thrombophilia and are associated with recurrent thrombosis and obstetric pathology. According 2006 classification criteria, serological markers of antiphospholipid syndrome (APS) include lupus anticoagulant, moderate and high levels of antibodies to cardiolipin (aСL) and â2-glycoprotein 1 (anti- â2-GP1) IgG and IgM. The task of standardizing aPL values remains unresolved, leading to variability in results.

Objective: to evaluate the comparability of IgG/IgM aCL and IgG/IgM anti- â2-GP1 measurement results using enzyme-linked immunosorbent assay (ELISA) and chemiluminescence (CLU) tests.

Material and methods. Peripheral blood from 192 patients (147 women and 45 men) was analyzed, 55 patients (29%) had primary APS, 12 (6%) had probable APS, 61 (32%) had systemic lupus erythematosus (SLE) and APS, and 64 (33%) had SLE without APS. IgG/IgM aCL and IgG/IgM anti- â2-GP1 were determined in all participants by ELISA. By CLU method IgG/IgM aCL were analyzed in 192 patients and IgG/IgM anti- â2-GP1 in 191 patients.

Results and discussion. The evaluation of the comparability of the results of ELISA and CLU revealed considerable discrepancies in the positive tests. Thus, in 16% of cases, a discrepancy was found in the levels of IgG aCL and IgM aCL by both methods (n=30 and n=31, respectively), in 18% in the level of IgG anti- â2-GP1 (n=34) and in 15% in the level of IgM anti- â2-GP1 (n=28).These discrepancies were to a greater extent associated with a more frequent detection of aPL in CLU when their values were negative in ELISA , indicating the greater information capacity of the CLU method.

However, a small number of patients were positive for aPL in ELISA but negative in CLU: 5 with IgG aCL, 4 with IgM aCL, 6 with IgG anti-â2-GP1, and 2 with IgM anti- â2-GP1 .

Conclusion. CLU is shown to be a more informative method for determining IgG aCL and IgG anti- â2-GP1 than ELISA (p<0.05).

Objective: To study the efficacy and safety of olokizumab (OKZ) in patients with rheumatoid arthritis (RA) in real-life clinical practice.

Material and methods. The observational program was conducted in 73 centers across Russia from Dec 1, 2022 to Jan 31, 2025. It was based on a retrospective analysis of real clinical practice data. Information on patients was collected and analyzed at baseline and after 1, 6, and 12 months of treatment.

Results and discussion. A total of 1,576 patients (81.7% women) with RA, aged 55.0 [44.0; 63.0] years and with RA duration of 100.0 [50.0; 156.0] months, were included in the program. After 6 and 12 months of OKZ therapy, the treatment target (remission/low activity) was achieved in 63.3% and 79.8% of patients by DAS28-CRP, and in 55.4% and 75.5% by CDAI respectively. Gender, age, seropositivity, and use of biologic disease-modifying antirheumatic drugs did not significantly affect the achievement of the treatment goal. During the observation period, a significant proportion of patients were able to discontinue glucocorticoids (GCs): 51.1% of patients received GCs initially, after 6 months, 27.6% of patients still received GCs, and after 12 months, 17.0%. During the observation, OKZ treatment was discontinued in 148 (9.5%) patients: in 50 (3.2%) patients due to insufficient efficacy, in 63 (4.0%) patients due to adverse events, and in 35 (2.2%) patients due to other reasons.

 Conclusion. IL-6 inhibition with OKZ is both effective and safe for achieving RA therapy goals in real-world clinical settings.

State-of-the-art management of ANCA-associated vasculitis (AAV) has significantly improved patient survival, but is associated with an increased risk of infectious complications, that currently are one of the leading causes of hospitalization and mortality in patients with AAV.

Objective: to assess the incidence and structure of comorbid infections in patients with AAV.

Material and methods. In this prospective cohort study, we enrolled 130 patients over 18 years of age diagnosed with AAV, including 87 patients with granulomatosis with polyangiitis, 32 with microscopic polyangiitis and 11 with eosinophilic granulomatosis with polyangiitis. In all patients primary medical records were analyzed, BVAS and VDI indices were calculated. Dynamic follow-up was performed monthly for 12 months. The primary endpoint in the study was an episode of infection registered at the next contact with the patient, secondary endpoints were severe infections.

Results and discussion. During the 12 months of follow-up in 130 patients 281 cases of various infectious diseases were reported (238 episodes of infections per 100 patient-years, 95% CI 209–270), with patients most commonly reporting episodes of upper respiratory tract infections. Among all infections, there were 23 cases (19.5 episodes per 100 patient-years, 95% CI 12.2–30.9) of severe infections in 14 patients and 3 deaths due to infectious complications.

Conclusions. The results of our study demonstrate a high incidence of infectious diseases including severe infections in patients with AAV and emphasize the relevance of infectious complications as a factor associated with adverse outcomes in patients with AAV.

Rheumatoid arthritis (RA) is an incurable but potentially controllable disease. The main goal of treatment is to achieve remission or low disease activity. Among difficult-to-treat patients, three groups are distinguished: patients whose treatment does not comply with the principle of “treat to target” (T2T) due to insufficient activity of the doctor, or due to non-compliance with the treatment regimen by the patient; cases where the central mechanisms of pain are not recognized; patients with “truly refractory RA.”

Objective: to evaluate the implementation of the T2T strategy in the real-world clinical practice of rheumatologists, and the physicians' understanding of the mechanisms of the development of a difficult-to-treat RA.

Material and methods. The study included three stages: 1) assessment of the duration of counting of DAS-28 index by doctors; 2) anonymous online survey of 43 rheumatologists from Yekaterinburg and the Sverdlovsk region; 3) assessment of patients' comprehension of the indicator “General activity of the disease”. The results of the study are presented in the form of descriptive statistics.

Results and discussion. The average counting time of the DAS28 is 1 min 16 s, but only 42% of rheumatologists calculated it correctly. The problem of physicians' insufficient attention to the subjective component of the DAS28 index and possible central sensitization as a cause of pain was revealed. Assessment of health is difficult and ambiguous for the patients.

Conclusion. The implementation of the T2T strategy in the treatment of patients with RA cannot be considered optimal today. Often the DAS28 index is used in a purely mechanical way without considering central sensitization, which can lead to overdiagnosis of the high inflammatory activity of RA as well as to unjustified changes in therapy.

Objective: to investigate the frequency of testosterone level lowering in men with systemic lupus erythematosus (SLE), and features of the SLE course, immunosuppressive therapy and metabolic disorders.

Material and methods. The cross-sectional continuous study included 38 men with SLE who were undergoing inpatient treatment in V.A. Nasonova Research Institute of Rheumatology. Patients' total testosterone level was determined, after which they were divided into groups with normal (>12 nmol/l) and reduced testosterone level. The patient groups were compared using the main indicators used in clinical rheumatological practice to assess the stage, activity and other medical and demographic characteristics of SLE, as well as purine and carbohydrate metabolism. Correlations between total testosterone level and some clinical and laboratory indicators were assessed.

Results and discussion. The frequency of testosterone deficiency in the studied group was 13.2%. Significant correlations of total testosterone level with prednisone dose (r=-0.56; p²; p=0.021) and dose of prednisone (15,0 [12,5; 20,0] vs 10,0 [5,0; 10,0] and also rarely took hydroxychloroquine compared to those with normal testosterone levels. In addition, in the clinical picture of SLE, there were less joint involvement, more frequent arterial hypertension and an increase in blood leukocytes level. In addition, a higher daily proteinuria value was found in patients with hypogonadism.

Conclusion. The relationship between testosterone level and prednisone dose in men with SLE has been demonstrated. Testosterone level and the presence of hypogonadism were not associated with the course and activity of SLE, but testosterone deficiency was associated with the presence of cardiometabolic disturbances as well as more pronounced proteinuria and less frequent joint involvement.

Objective: to investigate the frequency and characteristics of comorbid diseases in patients with late-stage ankylosing spondylitis (AS).

Material and methods. The study includes 40 men aged 33–67 with late-stage AS (main group) and 40 patients with a cardiovascular conditions (control group). We analyzed clinical characteristics of AS in patients of the main group. In addition, echocardiography (EcoCG) and ultrasound of brachiocephalic arteries (BCA) were done in patients of both groups to assess patients' cardiovascular condition.

Results and discussion. The mean age of the patients was 49.90±9.44 years, and the mean duration of the disease was 24.07±9.72 years. 85% of patients suffered from arterial hypertension (AH), mainly grade 1 and 2 (37.5% each). Body mass index >25 kg/m² was found in 55.0% (n=22) of patients, predominantly grade 1 and 2 (30.0%, n=12). Hypercholesterolemia was found in 62.5% of patients and an increase in lowdensity lipoprotein cholesterol in 57.5%. The incidence of diabetes mellitus (DM) was 10%. DM type 2 and LADA were found in a ratio of 1:1 (5.0% each). The differences in results of EcoCG and BCA ultrasound in the main and control group were not statistically significant.

Conclusion. AH and metabolic disorders occupy the leading place among cardiovascular diseases (CVD) in patients with stable spinal deformity, which can be considered as an additional risk factor for CVD. The data obtained indicate the need to assess cardiovascular risks at an early stage of AS to prevent CVD.

Genetic polymorphisms in ABCG2 gene (V12M; rs2231137 and Q141K; rs2231142) in patients with gout may determine the efficacy of colchicine for the prevention of arthritis attacks during the initiation of urate-lowering therapy. These data can be used in the development of a personalized approach for the treatment of patients with gout.

Objective: to evaluate the efficacy of colchicine in patients with gout with different missense genetic variants of the ABCG2 gene (V12M; rs2231137 and Q141K; rs2231142).

Material and methods. The study included 96 patients with gout who were randomized into the following groups: combined therapy with colchicine (Colchicine LIRKA) 0.5 mg/day and febuxostat 80 mg/day; colchicine (Colchicine LIRKA) 1.0 mg/day and febuxostat 80 mg/day; monotherapy with febuxostat 80 mg/day. The dosage adjustment of febuxostat and the assessment of the tolerability of the therapy were carried out in accordance with the Russian recommendations for the treatment of gout.

Genotyping of the ABCG2 gene polymorphisms (V12M; rs2231137 and Q141K; rs2231142) was performed in all patients. Patients were observed for 6 months; we compared the frequency of arthritis attacks and the intensity of pain according to the visual analogue scale (VAS) for different genotypes of the polymorphism 421C>A of the ABCG2 gene (rs2231142) and for the polymorphism V12M of the ABCG2 gene (rs2231137).

Results and discussion. 64% of patients had an CC genotype, 31% had the CA genotype and 5% had the AA genotype of polymorphism 421C>A of the ABCG2 gene (rs2231142). No significant differences in the frequency of arthritis flares (mean 0.3±0.7 and 0.6±1.0; p=0.2) and pain intensity during arthritis according to VAS (56.8±17.2 and 57.3±22.9 mm, respectively; p=0.9) were observed in carriers of the CC and CA/AA genotypes during the 6-month observation period. In the presence of the V12M polymorphism of the ABCG2 gene (rs2231137) 89% of patients had CC genotype and 11% had CT genotype. In carriers of the CC and CT genotypes, the frequency of arthritis flare-ups (median 0.4±0.9 and 0.7±0.8; p=0.3) and the intensity of pain according to VAS (56.8±19.7 and 67.5±18.5 mm, respectively, p=0.3) did not differ significantly.

Conclusion. Colchicine reduces the risk of arthritis flare-ups development. However, the hypothesis of a correlation between the inefficacy of the drug and the presence of different ABCG2 genotypes (V12M; rs2231137 and Q141K; rs2231142) was not confirmed.

Pain control is the most important task in the complex treatment of osteoarthritis (OA). One of the promising methods to increase the efficacy of analgesics in OA may be the combined use of nonsteroidal antiinflammatory drugs (NSAIDs) with a complex of vitamins B1, B6 and B12 (СVB).

Objective: to evaluate the efficacy of combination of NSAIDs + CVB compared to monotherapy with NSAIDs in the treatment of knee OA using a meta-analysis of randomized controlled trials (RCTs).

Material and methods. We selected articles during the period 1981–2024 years using electronic databases PubMed (English-language sources), eLIBRARY.ru (Russian-language sources) and Yandex search engine. The search yielded a total of 55 publications on this topic. RCTs investigating the efficacy of CVB in patients with OA were presented in 5 articles, of which only 3 had a unified design that included a comparison of the therapeutic effect of the combination of NSAIDs + CVB and NSAIDs monotherapy. These papers were included in the meta-analysis, in which the dynamics of pain intensity on the visual analogue scale (VAS) and the WOMAC index were evaluated. A weighted mean difference (WMD) and the heterogeneity of the data (index I²) were calculated.

Results and discussion. The meta-analysis included 3 RCTs (n = 298) with a duration of 3 to 8 weeks. The groups analyzed were homogeneous regarding the initial values of pain and the WOMAC index: the I² index was 0%. The analysis of these parameters after treatment showed a slight heterogeneity: the I² index for pain – 20%, for the WOMAC index – 39%. Initially there were no statistically significant difference between the main group (NSAID + CVB) and the control group (NSAIDs) in terms of pain level (by VAS): WMD=0.20 (95% CI, -0.05; 0.45). After treatment, the difference between the main and control groups in the dynamics of pain (by VAS) was statistically significant: WMD=-0.81 (95% CI -1.11; -0.50). Significant differences between the main and control groups in the baseline indicators and the dynamics of the WOMAC index were not found. No serious adverse reactions were detected in 3 RCTs.

Conclusion. According to the meta-analysis of 3 RCTs, the combination of NSAIDs + CVB in OA reduces the severity of pain more effectively than NSAIDs monotherapy.

Febuxostat (FS) is the drug of choice in impaired renal function, but the dosage regimen and the actual efficacy of the maximum allowable doses required to achieve the target uric acid (UA) level in patients with impaired renal function have not been adequately studied.

Objective: to compare the dosage of FS required to achieve the target level of UA in blood serum in patients with gout with normal or near normal (glomerular filtration rate (GFR) >60 ml/min/1.73 m²) and moderately impaired (GFR 30–60 ml/min/1.73 m²) renal function.

Material and methods. The study included 159 patients with gout who were not receiving urate-lowering medication and had serum UA levels above 360 μmol/l. The patients were divided into two groups: with GFR >60 ml/min/1.73 m² (n=123) and GFR 30–60 ml/min/1.73 m² (n=36). All patients were prescribed FS at a dose of 80 mg/day. If the target serum level of UA was not reached, the dose of the drug was increased to 120 mg/day. The observation period was at least 6 months (26 weeks).

Before the start and after the end of the observation period, complete blood count (CBC), serum levels of glucose, creatinine, UA, transaminases and creatine phosphokinase were assessed. GFR was calculated according to CKD-EPI formula. In two groups of patients, changes in UA serum levels, the probability of reaching the target UA level in the blood (<360 μmol/l) against the background of FS therapy and the dose of the drug required for this were analyzed.

Results and discussion. Data from 152 patients who completed the study were analyzed: 34 of 36 patients with GFR 30–60 ml/min/1.73 m² and 118 of 123 with GFR >60 ml/min/1.73 m². During the observation period, 129 (84.9%) of 152 patients reached the target level of serum UA: 101 (85.6%) of 118 patients with GFR >60 ml/min/1.73 m² and 28 (82.4%) of 34 with GFR 30–60 ml/min/1.73 m² (p=0.6). In the GFR >60 ml/min/1.73 m² group in 68 (67.3%) patients FS dose of 80 mg/day was enough to achieve the target level of UA and in 33 (32.7%) the dose of 120 mg/day was requires, and for the GFR 30–60 ml/min/1.73 m² group such doses were required in 13 (46.4%) and 15 (53.6%) patients, respectively (p=0.04). The dose of the prescribed drug after the adjustment until the target level of UA was reached was statistically lower in patients with GFR >60 ml/min/1.73 m² (93.1±18.9 mg/day) than in the group of patients with GFR 30–60 ml/min/1.73 m² (101.4±20.3 mg/day), p=0.04.

Conclusion. The efficacy of FS does not decline in patients with gout and moderate decline in renal function. In more than 80% of cases it is possible to achieve the target level of UA in these patients, but it is associated with the need to use the maximum daily doses of the drug.

We describe a patient with psoriatic arthritis (PSA) and palmoplantar psoriasis, resistant to standard therapy, who observed a significant decrease in disease activity on the background of upadacitinib at a dose of 15 mg/day. Remission was achieved by the 3rd month of treatment. No adverse phenomena were observed within 6 months of treatment.

Coxitis is one of the clinical manifestations of ankylosing spondylitis (AS). It is considered an unfavorable prognostic factor and plays a key role in patients' disability. As the disease progresses, total hip arthroplasty (THA) is indicated. It helps to improve functional status and quality of life, as confirmed by both short-term and long-term observations. However, there are still a number of issues related to THA that are being discussed: types of anesthesia care, choice of surgical access, positioning of acetabular component in ankylosis, the feasibility of tenotomy in unresolved hip contracture, the possibility of simultaneous surgery on both sides, the sequence of interventions in spinal ankylosis resolution in patients with AS. All these supports the need for further study of this problem.

Severe comorbid infections (SCI) are infections that develop against the background of the underlying disease and require hospitalization and/or intravenous administration of antibacterial drugs. In the structure of comorbid infections in patients with inflammatory joint diseases (IJD), the number of SCI does not exceed 4%. However, they are the direct cause of death in these patients. Various factors, including sociodemographic factors, as well as factors directly related to the IJD itself, including therapy, contribute to the development of SCI. This article discusses the incidence, structure and risk factors in patients with IJD.

The article summarizes modern data on the parvovirus (PV) B19 infection and associated conditions in rheumatological practice. Special attention is paid to the features of the structure and replication of the virus in infected cells of macroorganism, which contributes to a better understanding of the pathogenesis of the disease. The sequence of immune response formation during infection with PV B19 is considered. The issues of epidemiology of PV B19 infection, with outbreaks recorded approximately every 3 years, areraised. The possibility of a hemocontact route of transmission of PV B19 with IV drugs is emphasized. The course of PV B19 infection in immunosuppressed patients is described. The features of the clinical picture are presented and it is pointed out that the differential diagnosis of arthritis associated with PV B19 and rheumatoid arthritis is very difficult in the absence of the relevant epidemiological anamnesis.

Osteoarthritis (OA) is the most common disease of the musculoskeletal system. Protein complex, the NLRP3 inflammasome plays the key role in the pathogenesis of OA. It consists of three components: the sensor – NLRP3, the adaptor – ASC and the effector – caspase. Activation of the NLRP3 inflammasome promotes the synthesis of pro-inflammatory cytokines, interleukin (IL) 1 β and IL18, and the formation of gasdermin pores, which – combined – leads to cell death, pyroptosis. Despite successes in understanding the processes of OA development, there are no therapeutic methods that can completely stop or slow the progression of the disease. In addition, the use of some medications, particularly nonsteroidal anti-inflammatory drugs (NSAIDs), is associated with a clinically significant increase in the risk of NSAID-induced pathology by 50– 100%.

Due to increased life expectancy and the frequency of concomitant diseases, the treatment strategy for OA had to be changed, leading to the emergence of phenotypes of the disease characterized by low-intensity systemic inflammation.

We present a review of modern data reflecting the involvement of components of innate immunity in the development and progression of OA, as well as possible ways to correct disturbances taking these aspects into consideration.