Cytomegalovirus (CMV) infection is a common viral anthroponotic infection characterized by a variety of clinical and laboratory symptoms. There is a growing body of data on the association between CMV and the development of immune-mediated inflammatory rheumatic diseases (IIRD). The presence of immunopathological disorders caused both by the disease itself and using drugs with immunosuppressive effect determines the relatively high prevalence of comorbid active CMV in patients with IIRD. The commonality of the clinical picture of CMV infection and individual IIRDs often leads to problems in the diagnosis and differentiation between these diseases. The lack of recommendations for the rational use of antiviral drugs for therapeutic and prophylactic purposes in IIRD calls for further research.

Objective: The aim of the NiSaXPA study is to evaluate the quality of diagnosing, socio-demographic characteristics and treatment tactics of patients with axial psoriatic arthritis (axPsA) in real-world clinical practice in the Russian Federation.

Material and methods. The study involved 600 patients from 21 clinical centers in the Russian Federation.

Results and discussion. The diagnosis of axPsA was confirmed in 357 (59.5%) of 600 patients according to the centralized expert assessment. All 357 patients with axial lesions met criteria of the clinical guidelines for the treatment of patients with PsA. Of these, 201 (69%) patients had radiologically significant sacroiliitis (SI) according to Kellgren and 103 (59.2%) had active SI according to magnetic resonance imaging. The presence of syndesmophytes was confirmed in 119 (43.9%) patients. Inflammatory back pain was observed in approximately 80% of patients, most commonly in the lumbar and cervical spine. "Silent" sacroiliitis were found in 1.1–3.5 % of cases. 26.8% of patients were positive for HLA-B27. In the 6 months prior to the study, high PsA activity was present in 21.6% of patients according to the rheumatologist's assessment, while high activity according to the BASDAI index was found in 71.9 % of patients, and moderate and high activity according to the DAPSA index – in 82.7%. On the 24th week of observation, the number of patients with low activity according to BASDAI doubled and reached 66.3 %, while low activity and remission according to the DAPSA index amounted to 52.5% and 8.1% of patients, respectively. In most cases (about 27%), patients with axial manifestations were prescribed interleukin (IL) 17A inhibitors, about 14% of patients received tumor necrosis factor-α inhibitors, and about 4% received IL23 inhibitors.

Conclusion. In 40.5% of patients, axial skeletal involvement in PsA was over-diagnosed due to misinterpretation of clinical and imaging data. The vast majority of patients (77%) were treated with synthetic disease-modifying antirheumatic drugs, mainly methotrexate, which do not affect the activity of spondylitis. Biologic disease-modifying antirheumatic drugs (bDMARDs) were taken by 46.5% of patients. Switching therapy to bDMARDs led to a significant reduction in disease activity.

In order to improve the quality of medical care, the Russian clinical guidelines for the treatment of patients with PsA and the algorithms for the diagnosis of axial involvement need to be comprehensively implemented.

Objective. To report long-term safety and tolerability of olokizumab (OKZ) in combination with methotrexate (MTX) in subjects with active rheumatoid arthritis (RA), using pooled data from three randomised clinical trials (RCT) followed by open-label extension (OLE) study.

Methods. Cumulative data from three phase 3 core trials and their OLE were analysed. Safety variables assessed included treatment-emergent adverse events (AEs), serious AEs (SAEs), AEs of special interest and laboratory results. Efficacy assessments included ACR20/50/70 responses, Disease Activity Score 28 (C-reactive protein) <3.2, CDAI remission and low disease activity (LDA), SDAI remission and LDA, HAQ-DI decrease of 0.22 unit and Boolean 2.0 remission.

Results. A total of 2304 patients received OKZ in combination with MTX either once every 2 weeks or once every 4 weeks. Event rates per 100 patient-years in OKZ every 2 weeks and OKZ every 4 weeks, respectively, were 9.57 and 9.13 for SAEs; 2.95 and 2.34 for serious infections; 0.09 and 0.05 for gastrointestinal perforations; 0.58 and 0.83 for major adverse cardiovascular events; and 0.45 and 0.50 for malignancies. No increase in the rate of any AE was observed over 106 weeks of treatment. The evaluation of laboratory variables demonstrated the expected changes, like neutropenia, elevation of liver enzymes and blood lipids. Clinical response rates remained stable during the OLE.

Conclusion. The long-term safety and tolerability of OKZ in combination with MTX remained stable. The efficacy of OKZ was maintained through week 106. These findings support OKZ as a treatment option for patients with active RA.

The article discusses the results of a comparative phase III clinical trial of the efficacy and safety of the biosimilar Complarate (CPR; JSC Generium, Russia) and the reference drug Actemra (ACT; F. Hoffmann-La Roche Ltd., Switzerland) to assess their equivalence in patients with rheumatoid arthritis, RA (NCT06475508 clinicaltrials.gov).

Materials and methods. Male and female patients aged 18–75 years with RA with moderate to high disease activity and insufficient response to methotrexate (MTX) monotherapy and/or poor tolerability of MTX and/or insufficient response or intolerance to other standard DMARDs in combination with or without MTX were enrolled in the study. 464 (89.4%) patients were randomized in a 2:1 ratio into two groups. The study and the reference drug were administered as an intravenous infusion at a dose of 8 mg/kg once every 4 weeks. The primary endpoint was the proportion of patients with an ACR20 after 24 weeks of therapy.

Results and discussion. The proportion of responders in CPR group was 91.2%, and in ACT group – 90.7% (p = 0.866). The difference between the groups was 0.5% (95% CI: -5,2%−6,1%), which is fully within the declared boundaries of recognition of therapeutic equivalence. Comparability of the biosimilar CPR and the reference drug ACT is also confirmed by the results of secondary efficacy endpoints: the proportion of patients with ACR50/70, dynamics of the DAS28, SDAI, CDAI, the functional activity of patients (HAQ), laboratory parameters of inflammatory activity (ESR and CRP). Comparability of the study and the reference drugs is also demonstrated by the results of the safety analysis.

Conclusion. Based on the results of the clinical study, it has been proven that CPR (JSC Generium, Russia) is a biological analogue of ACT (F. Hoffmann-La Roche Ltd., Switzerland).

Identification of the non-radiological stage of axial spondyloarthritis (nr-axSpA) has contributed to the improvement of diagnostics and the expansion of therapeutic approaches in the early stages of the disease. However, there is still an unmet need for effective treatment of patients with active nr-axSpA.

Objective: to evaluate the dynamics of nr-axSpA in patients in the Kaliningrad region and to identify additional factors influencing the radiological progression of the disease.

Material and methods. A total of 68 patients with nr-axSpA were examined at baseline and during 3 year follow-up, most of them were women (62%). The median age of the participants was 27.5 [23.0; 33.3] years. The duration of diagnosis was 1 [1; 2] years. HLA-B27 antigen positivity was present in 40% of cases. Patients at baseline and during follow-up underwent a standard clinical and laboratory examination, pelvic radiography and magnetic resonance imaging of the sacroiliac joints. In addition, cytokine levels (visfatin, PPM1A, MIF, serum calprotectin) and the concentration of IgCD74 antibodies were determined.

Results and discussion. After 3 years of follow-up, the diagnosis still met the criteria for nr-axSpA in 30 (44.1%) of the 68 patients, in 16 (23.5%) it transformed into radiographic axSpA (r-axSpA), in 7 (10.3%) – to axial psoriatic arthritis, in 13 (19.1%) the clinical picture no longer met the criteria for nr-axSpA, 2 (3%) patients dropped out of the study. When analyzing the values of visfatin, PPM1A, MIF and serum calprotectin, no differences were found between nr-axSpA and r-axSpA, while the average concentrations of IgCD74 antibodies were slightly higher in patients with nr-axSpA (7.4 and 5.0 ng/ml respectively). It was shown that the probability of radiological progression from nr-axSpA to r-axSpA increased 3.308-fold with a one-unit increase in the ASDAS (Ankylosing Spondylitis Disease Activity Score) index.

Conclusion. The median duration of nr-axSpA diagnostics in the Kaliningrad region was 1 year. In terms of dynamics, after 3 years of observation, 44.1% of patients still met the criteria for nr-axSpA, and radiological progression to r-axSpA was observed in 23.5% of cases. High values of the ASDAS index and its increase by 1 unit increased the speed of radiological progression of nr-axSpA by 3.308 times. The difficulties in the early diagnosis of axSpA in practice necessitate the establishment of reference centers to obtain expert opinions on issues of differential diagnosis and treatment choices in patients with nr-axSpA and ankylosing spondylitis.

Literature data suggest that HLA alleles may be associated with the development of Sjögren's syndrome (SS) and the production of autoantibodies against the Ro/SSA and La/SSB antigens. However, such studies have not been conducted in Russia.

Objective: to study the association between alleles of the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and the risk of developing SS and the production of autoantibodies.

Material and methods. The study included 80 patients with SS or Sjögren's disease (SD). All patients met the ACR/EULAR criteria, 2016. AntiRo/SSA and anti-La/SSB autoantibodies were detected in 67 patients (83.8%), 37 patients had the combination anti-Ro/SSA/anti-La/SSB, 30 patients had only anti-Ro/SSA, and 13 patients did not have these antibodies. The control group consisted of 160 healthy blood donors without autoimmune diseases and without a family history of autoimmune diseases, who were comparable in gender and age to the patient group. High-throughput sequencing of the alleles of the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes was performed on the Illumina MiSeq platform using the MiSeq Reagent Kit v3. To amplify the exons of the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes, 56 specially designed primers containing Illumina adapters at the 5’ ends for subsequent indexing were used. Statistical data processing, including comparison of the frequencies of HLA alleles in the group of patients with SS/SD and in the control group, was performed in the Python software environment using the Numpy, Pandas and scikit-learn libraries.

Results and discussion. In the group of patients compared to the control group we observed an increase in frequency for the alleles HLA-A*01:01:01 (OR=3.28, 95% CI [1.90–5.67], p <0.001), B*08:01:01 (OR=5.41, 95% CI [3.00–9.82], p<0.001), C*07:01:01 (OR=5.12, 95% CI [2.57– 10.19], p<0.001). In addition, all 2-, 3- and 4-allele combinations were significantly more frequent in the patient group compared to the controls. The most significant combinations of alleles as risk markers for the development of SS were the 2-allele haplotype B*08:01:01-DRB1*03:01:01 (OR=6.65, 95% CI [3.37–13.14], p<0.001) and the 4-allele haplotype A*01:01- B*08:01-C*07:01-DRB1*03:01 (OR=6.05, 95% CI [2.71–13.51], p <0.001). The most significant correlation between the production of two autoantibodies anti-Ro/SSA/anti-La/SSB was found for the haplotypes B*08:01:01-DRB1*03:01:01 (OR=9.50, 95% CI [4.16–21.70], p<0.001) and A*01:01:01-B*08:01:01-C*07:01:01-DRB1*03:01:01 (OR=7.20, 95% CI [2.81–18.43], p <0.001). In the group of 30 patients who only produced anti-Ro/SSA, the association with the above-mentioned haplotypes was less pronounced, although it remained high. Small sample of patients without anti-Ro/SSA and anti-La/SSB (13 patients), did not allow to determine statistically significant associations with HLA alleles/haplotypes.

Conclusion. A statistically significant association was found between several HLA alleles/haplotypes belonging to ancestral haplotype 8.1 (AH 8.1) as markers of susceptibility to SS and the production of Ro/SSA and La/SSB autoantibodies.

Objective: to assess the level of serum calprotectin (CLP) in Behcet's disease (BD).

Material and methods. The study included 90 patients with BD (35 women and 55 men) and 30 healthy controls (22 women and 8 men). The mean age of the BD patients was 32 [26; 37] years, that of the control subjects was 30 [25; 37] years. Serum CLP levels were measured with an enzyme immunoassay using a reagent kit from Bulhmann Laboratories AG (Switzerland). Results and discussion. CLP levels were statistically significantly higher in patients with BD compared to healthy controls (median 4.08 [2.81; 7.25] vs. 2.86 [2.15; 3.92] μg/ml; p=0.003). Elevated serum CLP levels were found in 23 (26%) of the 90 patients with BD. Patients with high CLP levels were more likely to have active uveitis (odds ratio, OR 4.741; p=0.011), pustulosis (OR 3.41; p=0.044), arthritis (OR 13.89; p=0.014) and high BD activity (OR 3.195; p=0.029). A direct correlation was found between CLP level and BDCAF activity index (rs=0.415, p<0.0001), CRP (rs=0.466, p <0.0001) and ESR (rs=0.357, p=0.001).

Conclusion. Serum CLP levels are elevated in patients with BD and are associated with high disease activity, active uveitis, pustulosis and arthritis.

Objective: a comparative evaluation of the effect of the interleukin-17A inhibitor (iIL) netakimab (NTK) and methotrexate (MTX) on laboratory markers of endothelial dysfunction in patients with psoriatic arthritis (PsA) in comparison with the dynamics of clinical efficacy indicators during 6 months of therapy.

Material and methods. We performed a dynamic observation of 66 patients with PsA who were prescribed MTX and NTK for the first time. Thirty of them (group 1) received MTX 15 mg/week in the form of subcutaneous (s/c) injections in combination with folic acid 5 mg/week orally; 36 patients (group 2) received NTK as s/c injections at a dose of 120 mg at weeks 0, 1 and 2, and then once every 2 weeks until week 14, from week 14 – once every 4 weeks. The control group consisted of 20 substantially healthy individuals without skin diseases, rheumatic immune-inflammatory diseases of the musculoskeletal system and clinically significant diseases of the cardiovascular system. The clinical data were analyzed before, 3 and 6 months after the start of treatment. In all patients, the concentration of vascular endothelial growth factor (VEGF), endothelin 1 (En-1) and nitric oxide (NO) was analyzed before the start of treatment and at the end of the third month of treatment.

Results and discussion. The concentration of laboratory markers for endothelial dysfunction was increased in patients with PsA compared to the control group: the median value of VEGF was 19.8 [4.5; 49.4] and 5.2 [0.5; 9.8] pg/ml (p=0.004), En-1 – 286.4 [154; 439] and 96.5 [32; 188] pg/ml (p=0.002), NO – 4.3 [2.1; 12.5] and 2.2 [0.2; 5.0] pg/ml (p=0.02), respectively. By the end of the 3rd month of therapy, a decrease in the concentration of indicators of endothelial dysfunction was observed. The dynamics of VEGF and En-1 concentrations was more pronounced in patients receiving NTK during the first 3 months of treatment than in patients receiving MTX treatment. The median decrease in VEGF concentration was 10.2 [8.4; 13.7] and 7.0 [5.6; 11.7] pg/ml (p=0.043), in En-1 – 184.6 [167; 202] and 112.7 [97; 136] pg/ml (p=0.008), respectively. A more significant decrease in LEI, PASI and NAPSI was achieved when NTK was used for 3 and 6 months compared to MTX therapy.

Conclusion. The work demonstrated the ability of NTK, iIL17A, to reduce the initially elevated levels of laboratory markers of endothelial dysfunction.

Interest to the topic of coronavirus infection remains unabated. At the same time, there is insufficient information in the literature on the clinical course of COVID-19 in systemic sclerosis (SSc), a systemic autoimmune disease associated with high mortality.

Objective: to identify the characteristics of coronavirus disease in SSc and risk factors for severe COVID-19 and death.

Material and methods. A retrospective analysis of data from patients with SSc was performed. The analyzed cohort included patients from the registry of the Systemic Sclerosis Laboratory of V.A. Nasonova Research Institute of Rheumatology. Information about the history of novel coronavirus infection was obtained by telephone interview 10 months after the outbreak of the pandemic. COVID-19 was diagnosed if there was a positive oral cavity/nasopharynx PCR swab, if antibodies to SARS-CoV-2 were present and/or characteristic symptoms and computed tomography (CT) changes in the lungs were present.

Results and discussion. COVID-19 was diagnosed in 57 (52%) patients with SSc. Their median age was 58 [31; 79] years. The majority were women (n=48, 84%) with a limited form of SSc (n=37, 65%). Fifteen (26%) patients had diffuse, 4 (7%) had overlapping (SSc-polymyositis and SSc-rheumatoid arthritis) and 1 (2%) had visceral SSc. Almost 2/3 (74%) of patients with COVID-19 had SSc associated with interstitial lung disease (ILD), with 40% of them having >20% lung parenchymal involvement.

All patients received low-dose prednisone therapy, 95% received immunosuppressive therapy and in half of the cases mycophenolate mofetil; rituximab was used in 40% of patients.

Chest CT scan was performed in 51 (89%) patients. Pneumonia caused by the new coronavirus infection was detected in 46 (90%) of them: CT1 (up to 25% lung involvement) – in 10 (20%), CT2 (25–50% involvement) – in 21 (41%) and CT3 (50–75% involvement) – in 15 (29%); in 5 (10%) cases no changes were detected on CT.

Mild and moderate course of the viral infection was observed in 19 (33%) and 18 (32%) patients respectively, severe infection – in 20 (35%), including fatal cases in 12 (21%).

Conclusion. Patients with SSc infected with SARS-CoV-2 are at risk of severe coronavirus infection, often due to the association of the underlying disease with ILD and the use of immunosuppressive therapy, including biologic disease-modifying antirheumatic drugs. In case of COVID-19 development the high incidence of cardiovascular and pulmonary comorbidities that characterize SSc may contribute to a decrease in the efficacy of therapy for both the underlying disease and coronavirus infection, generally worsening the prognosis in these patients.

With the advent of more effective conservative methods of treating rheumatoid arthritis (RA), patients with severe hand deformities are being treated less and less by orthopaedic surgeons. However, when significant changes occur in the hand joints, surgery is the only method to restore their function. The previously widespread arthrodesis procedures are gradually giving way to modern soft tissue joint-preserving surgeries that prevent the development of severe deformities and preserve hand function.

Objective: to compare the functional outcomes of extensor carpi ulnaris and extensor carpi radialis longus transposition surgery (ECU+ECRL) and wrist joint arthrodesis in patients with RA.

Material and methods. The study included 58 patients with a confirmed diagnosis of RA. Most patients (93%) were women with a disease duration of 4 to 6 years, the mean age was 46.3±14.6 years. All patients were seropositive for rheumatoid factors, most had radiological stages III and IV of RA according to Steinbrocker, radiological stage IV according to Larsen. Most of the patients had moderate disease activity. From 2021 to 2023, 21 patients underwent ECU + ECRL surgery and 37 patients underwent arthrodesis of the wrist joint. The groups were comparable in terms of key clinical characteristics. The average follow-up time after surgery was 6 months.

Results and discussion. The mean DASH score in the transposition group (ECU + ECRL) was 38.3±10.12, while in the arthrodesis group it was 47.45±16.92 (p <0.05). In the late postoperative period (after 6 months), all patients showed a positive dynamics according to the visual analogue scale, which was comparable in both groups: in the ECU + ECRL group – 2.66±1.49 cm, in the arthrodesis group – 3.0±1.6 cm. The range of motion of the wrist was significantly greater in the ECU + ECRL group than in the arthrodesis group (p <0.05). At the follow-up examination in the postoperative period, a significant improvement in quality of life according to the EQ-5D was found in both the ECU+ECRL group (0.686) and the arthrodesis group (0.625), p<0.05.

Conclusion. X-shaped extensor tendon plastic surgery for wrist joint stabilization should be considered a promising technique that can reduce pain and improve patients' functional status and quality of life.

We present a clinical case of the development of subtotal pneumofibrosis associated with the progression of systemic sclerosis in a patient previously infected with COVID-19. Investigating the possible relationship between these conditions is important both for understanding the current therapeutic algorithm and for further aetiopathogenetic studies on the nature of rheumatic diseases.

Vasculitis associated with antineutrophil cytoplasmic antibodies (AAV) is a potentially dangerous autoimmune disease characterized by necrotizing inflammation of small blood vessels. In the pathogenesis of AAV, both innate and adaptive immunity are closely linked to neutrophil function. The study of the pathogenetic mechanisms of neutrophil activation in AAV may serve as a prerequisite for the development of more accurate and modern methods of laboratory diagnostics as well as new treatment approaches targeting neutrophils. The review presents an analysis of studies addressing the issue of neutrophil activation in AAV.

The article discusses the use of bioanalogues (BAs) in the treatment of rheumatoid arthritis using the example of the comparable efficacy, tolerability and immunogenicity of the original biologic disease-modifying antirheumatic drug (bDMARD) etanercept (ETC) and its BA GP-2015. We discuss the maintenance of the improvement achieved when switching from the original ETC to BA. Recommendations of international experts and preliminary recommendations of the Association of Rheumatologists of Russia on the use of BA are given. The frequency of development and negative consequences of the nocebo effect when switching patients to BA are described. Data from randomized controlled trials and clinical practice on the safety of switching patients from original biologics to BA are presented. The economic benefits of introducing BA into the clinical practice of rheumatologists in Europe and Russian Federation are considered.

Avascular osteonecrosis (AON) is a common condition that can occur at any age, but more often in young and able-bodied people. The disease leads to rapid destruction and collapse of the subchondral bone with subsequent formation of secondary osteoarthritis of the affected joint. The review presents modern methods of instrumental diagnostics of AON. Particular attention is paid to the detection of stage I AON. An approach to early diagnosis of AON is discussed that may change the misconception of viewing bone tissue edema as a sign characteristic only of AON and may improve differential diagnosis of the disease from other conditions and treatment outcomes.

The interdisciplinary council of leading experts has presented recommendations for the effective and safe use of non-steroidal anti-inflammatory drugs in osteoarthritis and non-specific back pain in general outpatient practice.

Despite the successes of conventional medicine, the search for optimal remedies for the treatment of osteoarthritis does not lose its relevance. Currently, new combination products are entering the market, combining well-studied pharmaceutical ingredients such as glucosamine and chondroitin sulfate with well-known and promising new nutraceutical components. Pharmaconutraceutical Theraflex Ultra refers to such drugs, and the possibilities of its effect on the symptoms and quality of life of patients are of great interest. To study the effect of Theraflex Ultra on clinical symptoms in comparison with the well-known drug Theraflex, an open randomized comparative observational study was organized at the V.A. Nasonova Research Institute of Rheumatology. Currently, intermediate results have been obtained after 1 month of using Theraflex Ultra, which demonstrate pronounced benefit and relief of symptoms, improvement of quality of life.

On September 7, 2024, as part of the scientific program of the VII Eurasian Congress of Rheumatologists in Kyrgyzstan, a symposium "Trio for the preservation of joint health" was held with the support of "Heel RUS" LLC, at which doctors from Russia, Kyrgyzstan, Uzbekistan, Kazakhstan and other countries discussed modern views on the diagnosis and treatment of osteoarthritis (OA). Rehabilitation techniques for OA were also presented.