Phosphopenic osteomalacia (PPOM) is a rare variant of paraneoplastic syndrome caused by tumor synthesis of fibroblast growth factor 23 (FGF23). FGF23 secretion leads to a decrease in phosphate reabsorption and calcitriol levels, which leads to the development of severe hypophosphataemia and hypocalcaemia. FGF23 synthesis is predominantly associated with benign mesenchymal tumors, but has also been described in malignant neoplasms. The main clinical manifestations of PPOM are generalized myalgias and myopathy, ostealgia, pathological fractures, etc. The diagnosis of the disease requires a step-by-step investigation using somatostatin receptor-based imaging techniques, as these have the highest sensitivity for the detection of neoplasms causing osteomalacia. Surgical intervention is clearly the treatment of choice. Promising non-surgical methods include treatment with burosumab and somatostatin analogues.

Objective: to characterize patients with difficult-to-treat (D2T) psoriatic arthritis (PsA) and to assess risk factors for its development.

Material and methods. The study included 263 PsA patients treated with biologic disease- modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) and followed up for ≥2 years in the All-Russian Registry of PsA Patients. All patients underwent a standard clinical and laboratory examination, and concomitant diseases were recorded. PsA activity was assessed using DAPSA index and minimal disease activity criteria.

Results and discussion. 152 (57.8%) patients who received 1 bDMARD/tsDMARD for 2 years achieved remission/low disease activity (LDA) according to DAPSA and were categorized as having non-D2T PsA. Other 111 (42.2%) patients switched ≥2 bDMARDs/tsDMARDs within 2 years, 71 (27%) of them achieved remission/LDS, and 40 (15.2%) patients who continued to have high or moderate PsA activity met the D2T criteria. A comparative analysis of 40 patients (20 men and 20 women) with D2T PsA and 152 patients (78 men and 74 women) with PsA who did not fulfil the D2T criteria was performed. It was found that patients with D2T PsA had a significantly longer duration of PsA (p=0.017), more frequent polyarthritis (p=0.014), dactylitis (p=0.004), enthesitis (p=0.001), BSA >10% (p=0.008), onycholysis (p=0.001), HAQ >0.5 (p=0.039), depression (p=0.007) and elevated blood uric acid levels (p=0.023).

Conclusion. In real-life clinical practice, the D2T variant of PsA is reported in 15% of cases. Treatment-resistant PsA patients are characterized by a longer duration of PsA, more widespread severe psoriasis with onycholysis and are more likely to have polyarthritis, dactylitis, enthesitis and functional disorders at the time of bDMARD prescription, as well as concomitant diseases, especially depression and hyperuricaemia.

Objective: to compare the frequency of comorbid diseases in axial psoriatic arthritis (axSpA) and in other variants (OV) of axial spondyloarthritis (axSpA).

Material and methods. We studied 60 patients, 30 with axPsA (15 men and 15 women, mean age – 49.1±10.4 years, disease duration – 12.6±6.9 years) and 30 with OV axSpA (16 men and 14 women, mean age – 42.9±9.7 years, disease duration – 16.30±8.3 years). All patients underwent a standard rheumatological examination. The diagnosis of comorbid diseases was confirmed using ICD-10 codes. The Cumulative Illness Rating Scale (CIRS), Charlson comorbidity index (CCI) and the weighted version of Functional Comorbidity Index (w-FCI) were used to assess comorbidity.

Results and discussion. Comparative analysis of the two groups revealed that axPsA patients were older than OV axSpA patients (p <0.05). Occurrence of back pain before the age of 40 was observed in 60% of axPsA cases, compared to 86.7% in OV axSpA (p<0.05). The limitation of spinal and hip mobility was less severe in axPSA than in OV axSpA. The median side flexion was 12.3 [10; 15] and 9.5 [8; 11] cm, the Schober test was 4.2 [3; 5] and 3.0 [2; 4] cm and intermalleolar distance was 95.9 [86; 102] and 83.0 [75; 100] cm, respectively (p<0.05). Patients with axPsA were more likely to have peripheral arthritis compared to patients with OV axSpA: 27 (90%) and 11 (36.7%) cases, respectively (p<0.05) and higher laboratory indices of activity: median ESR, 31.9 [10; 38] and 20.4 [5; 14] mm/h, and CRP, 20.5 [2.8; 20.7] and 13.6 [0.9; 12.0] mg/L, respectively (p<0.05). In the axPsA and OV axSpA groups, circulatory system diseases were found in 50 and 50% of patients, metabolic disorders in 76.6 and 76.6%, and gastrointestinal diseases in 46.7 and 70 %. Obesity was more common in axPsA than in OV axSpA – in 40 and 16.7% of patients, respectively (p<0.05).

Conclusion. A high frequency of comorbidities, mainly cardiovascular and metabolic diseases, was found in both groups. These data should be considered in the choice of therapy and optimization of existing treatment algorithms.

The progressive course of systemic lupus erythematosus (SLE) with high activity and severe internal organs involvement requires the prescription of expensive biologic disease-modifying antirheumatic drugs (bDMARDs), rituximab (RTM) and belimumab (BLM), whose comparative clinical and economic efficacy has not been adequately studied.

Objective: to evaluate the clinical and economic efficacy of RTM and BLM therapy in patients with SLE.

Material and methods. The study included 50 SLE patients who were divided into two groups and received RTM (group 1, n=25) or BLM (group 2, n=25) therapy for 12 months. The clinical and economic analysis was performed with the cost-effectiveness method using the cost-per-responder (CPR) model. A clinically significant improvement in SLEDAI-2K (Systemic Lupus Erythematosus Disease Activity Index modified 2K; Δ ≥4) was considered a response to therapy. Direct and indirect costs were considered in the analysis.

Results and discussion. Against a background of therapy, there was a decrease in SLE activity with a decrease in median SLEDAI-2K in group 1 from 12 [10.5; 18] to 8 [4; 10] and in group 2 from 10 [8; 14.5] to 4 [2; 4] (p< 0.001 in both cases). A clinically significant improvement was observed in 56% of patients in group 1 and 72% of patients in group 2. The peculiarities of the BLM dosing regimen caused higher (1.7 times) total costs than in the case of RTM. According to the CPR value, RTM showed a greater benefit (1.3 times) than BLM (954 thousand rubles versus 1.25 million rubles). The incremental cost-effectiveness ratio (ICER) was 1.4 million rubles, which does not exceed the threshold of willingness to pay for a domestic patient.

Conclusion. When comparing BLM and RTM therapy for SLE patients in real-life clinical practice, greater clinical and economic efficiency was demonstrated for RTM. BLM therapy was found to be “cost-effective”.

Objective: to investigate feasibility of using ultrasonography (US) to evaluate structural changes of salivary glands (SG) in patients with Sjögren's disease (SD).

Material and methods. The study included 159 patients who were examined in V.A. Nasonova Research Institute of Rheumatology from 2016 to 2022 who met V.A. Nasonova Research Institute of Rheumatology 2001, and/or ACR 2012, and/or ACR/EULAR 2016 criteria for SD, and who had not previously received immunosuppressive therapy. All patients underwent a comprehensive classical examination (ophthalmological, dental, immunological) to diagnose SD. Disease activity was determined using ESSDAI index. US of the parotid gland (PG) and submandibular SGs was performed using a GE LOGIQ 9 device, and the images obtained were scored according to the OMERACT SGUS scoring system (SGUS SS).

Results and discussion. All SGUS SS scores statistically significantly correlated (p<0.05) with mouth sicca symptoms, enlargement of PG, ESSDAI activity index, presence of lymphohistiocytic infiltrate and focus score in labial SG biopsy, and parenchymatous parotitis according to sialography. No significant correlation was found with the results of sialometry. There was a significant correlation between the changes detected by US and sialography (r=0.422; p=0.001). Considering the data obtained, the consistency of the results of the different examination methods was analyzed. Bland-Altman diagrams were created to reflect the dependence of the differences between the results of US and sialography. At various stages of the comparison, not all data points were within the standardized range. In addition, 5% of the parameters were not within the interval of two standard deviations. The Bland-Altman analysis revealed a systematic discrepancy indicating a low degree of agreement between the two methods for determining structural changes in SG. According to the ROC analysis, sensitivity of ultrasound was 94% and specificity 51%. The area under the curve (AUC) was 0.787 (95% confidence interval 0.700–0.875).

Conclusion. SG US and sialography are not interchangeable, but complement each other in the assessment of SG structure. SG US is a safer and non-invasive method of SG examination that does not require contrast agent administration and is likely to play an important role in the dynamic monitoring of patients during the therapy. However, sialography is a more accurate method of diagnostics and assessment of the extent of SG lesions.

Several studies have shown that systemic rheumatoid inflammation may cause induction and accelerated progression of atherosclerotic vascular lesions, which in turn may lead to more frequent development of cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) compared to the general population.

Objective. To evaluate the presence, nature and role of conventional and RA-specific risk factors for the development of CVD in patients with active RA in real-life clinical practice.

Material and methods. Data from 967 patients with confirmed active RA were analyzed. Biologic disease-modifying antirheumatic drugs (DMARDs) or targeted DMARDs were prescribed/switched due to the ineffectiveness of previous therapy. Patients were divided into two groups: with and without CVD. In addition, comparable age subgroups of elderly (60–74 years) and middle-aged (45–59 years) patients were formed in each group. In all patients, clinical and laboratory parameters of RA activity, presence of extra-articular manifestations, the severity and progression of RA and characteristics of pharmacotherapy were analyzed. In addition, concomitant diseases and several traditional risk factors for the development of CVD were analyzed in all RA patients.

Results and discussion. In patients with similar RA activity and duration, there is a parallel, tatistically significant accumulation of traditional CVD risk factors with increasing age-related CVD. The incidence of arterial hypertension, diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, thyroid pathology, anemic syndrome, dyslipidemia, hyperuricemia and obesity was significantly higher in the group of elderly RA patients with CVD than in the group of middle-aged patients.

Conclusion. It seems appropriate to identify a specific variant of RA that is closely associated with atherosclerosis.

Objective: to investigate the efficacy and safety of olokizumab (OKZ) in patients with rheumatoid arthritis (RA) over a 12-month period after switching from interleukin (IL)-6 receptor inhibitors (iIL6R) for non-medical reasons.

Material and methods. A retrospective cohort study conducted in 11 centers in the Russian Federation included 110 patients with confirmed diagnosis of RA according to 2010 ACR/EULAR criteria. In all patients in early 2022 (due to problems with drug supply during the coronavirus pandemic) iIL6R were switched for non-medical reasons to OKZ at a dose of 64 mg once every 2 weeks or once every 4 weeks in accordance with the instructions for the medical use of OKZ.

Data on clinical efficacy, safety and changes in the dosing regimen of the drugs over an observation period of one year are presented. We assessed the dynamics of the clinical indicators: number of painful and swollen joints, pain on a visual analogue scale and DAS28-ESR/CRP indices. Routine laboratory tests included assessment of red and white blood cells count, ESR, hemoglobin, CRP, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin and cholesterol. Adverse events (AEs) were recorded in accordance with standard practice.

Results and discussion. After 6 months of therapy, the proportion of patients who achieved remission/low disease activity according to DAS28-ESR and DAS28-CRP decreased to 70.1% and 72.9%, respectively, and the proportion of patients with moderate and high activity according to DAS28-ESR increased to 26.1% and 3.7%, respectively, and according to DAS28-CRP to 21.5% and 5.6 %, respectively. After 12 months, remission/low disease activity according to DAS28-ESR and DAS28-CRP was achieved in 81.4% and 83.5% of patients, respectively, and 18.6% and 16.5% of patients had moderate activity.

In the OKZ monotherapy group, after 6 months of treatment 22 (71.0%) patients were in remission/low disease activity according to DAS28-ESR and 23 (74.2%) patients according to DAS28-CRP. After one year of observation, remission/low disease activity according to DAS28-ESR and DAS28-CRP had 24 (88.9%) and 23 (85.2%) patients, respectively.

In the combined therapy group of OKZ + disease-modifying antirheumatic drugs (DMARDs), remission/low disease activity according to DAS28-ESR was observed in 53 (70.7%) patients and according to DAS28-CRP – in 55 (73.3%) patients by the 6th month of therapy. After 12 months, in this group 55 (78.6%) patients showed remission/low disease activity according to DAS28-ESR and according to DAS28-CRP – 58 (82.9 %) patients.

After 6 months, 107 (97.3 %) out of 110 patients included in the study continued treatment. In 1 (0.9%) case OKZ was discontinued due to insufficient effect, in 2 cases contact with the patients was lost. After 12 months, therapy was continued in 97 (88.2%) patients. In 5 (4.5%) cases treatment was discontinued due to insufficient efficacy, in 2 (1.8%) cases – due to increased AST/ALT levels, in another 2 (1.8 %) cases – for non-medical reasons, and in 1 case contact with the patient was lost.

Conclusion. OKZ, a direct IL-6 inhibitor, provided effective control over RA symptoms after switching from iIL6R, which allowed to achieve the treatment goal of maintaining remission/low disease activity over 1 year in more than 80% of patients. OKZ has demonstrated a broad spectrum of capabilities in real-world clinical practice, even when used as monotherapy. In terms of safety profile, OKZ was comparable to other IL6 inhibitors.

Objective: to evaluate the efficacy and safety of the biosimilar etanercept (ETC, Altebrel) in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA) in clinical practice.

Material and methods. The study included 20 patients with a confirmed diagnosis of RA and 8 with SpA: 5 with axial SpA with radiological signs of sacroiliitis (r-axSpA), 3 with peripheral psoriatic arthritis (PsA). The mean age of the patients with RA was 47.7±12.3 years, and the mean age of SpA patients was 40.4±15.9 years. Patients with RA had moderate or high disease activity: mean DAS28-ESR index 5.2±1.0, median CDAI – 22.5 [15.5; 35.0], SDAI – 31.9 [24.4; 38.6], CRP level – 11 [0.9; 32.5] mg/L. Patients with r-axSpA had high activity and functional impairment, the median BASDAI was 5.5 [3.5; 8.0], BASFI – 6 [4; 6], CRP level – 17.5 [12.5; 27] mg/L. In PsA, the average DAS28 was 6.25±0.71. All patients were prescribed Altebrel at a dose of 50 mg subcutaneously weekly against a background of disease-modifying antirheumatic drugs. Patients were examined at baseline and then after 3 and 6 months of treatment.

Results and discussion. During treatment with the biosimilar ETC, all patients with RA showed a decrease in inflammatory activity markers: after 3 and 6 months of therapy, the mean DAS28-ESR value decreased to 3.5±1.2 and 2.3±0.7 (p <0.001) the median SDAI value to 19.6 [6.9; 32.5] and 8.4 [4.7; 15.6] (p<0.001), CDAI value to 9.5 [4; 13.0] and 4.5 [3.0; 7.5] (p <0.001), the CRP level – to 5.0 [0.7; 21.9] and 5.0 [2.0; 10.9] mg/L (p<0.001), respectively. Patients with SpA showed a decrease in disease activity and an improvement in functional status: the median BASDAI decreased to 1.0 [0; 2.5] and 0 [0; 1.5], BASFI to 0 [0; 1] and 0 [0; 0], CRP level to 4.5 [2.5; 6.5] and 2.0 [2.0; 2.5] mg/L, respectively. In patients with PsA, DAS28 decreased on average to 2.92±0.12 after 3 months, and after 6 months the values were 1.74 and 2.29 in 2 patients.

All patients completed the study and no adverse events were observed during treatment. According to EULAR criteria, a good response was achieved in 40% of patients with RA after 3 months, and in 80% after 6 months, and a satisfactory response in 20%. Patients with r-axSpA showed statistically significant positive dynamics of BASDAI and BASFI indices as well as normalization of laboratory activity parameters.

Conclusion. The results of the study demonstrate the high efficacy of Altebrel in rheumatic diseases, including RA and SpA.

Chronic post-traumatic pain (CPTP) is diagnosed when pain persists for ≥3 months after injury. This is a serious condition that significantly limits patients' quality of life and ability to work and is one of the predictors of the development of post-traumatic osteoarthritis.

Objective. To investigate the clinical features of CPTP after knee injury.

Material and methods. The study group comprised 103 patients (mean age 39.4±12.5 years, 51.5% women). All patients had a knee injury with diagnosed involvement of the anterior cruciate ligament and/or meniscus and suffered from pain ≥1 month after the injury ≥4 points on the numerical rating scale (NRS, 0–10). Patients were assessed after 3 and 6 months. Pain intensity during movement, at rest and at night and functional impairment were assessed using NRS. KOOS, EQ-5D, PainDETECT, CSI, Pain Catastrophizing, HADS, FIRST and FACIT questionnaires.

Results and discussion. After 3 months, the number of patients with CPTP was 33 (32.0%). After 6 months, these patients had significantly more severe symptoms than patients with knee injuries without CPTP (control group, n=70). In the CPTP and control groups, the median pain during movement was 5.0 [4.0; 6.0] and 1.0 [0.0; 1.0] respectively, p12 was found in 24.2 and 2.9% of cases, p <0.001 ; pain at rest – 2.0 [2.0; 3.0] and 0.0 [0.0; 1.0], p <0.001 <0.001;; pain at night – 2.0 [1.0; 3.0] and 0.0 [0.0; 0.0], p <0.001; KOOS score – 4.0 [1.0; 5.5] and 2.0 [1.0; 3.5], p <0.001; quality of life according to EQ-5D – 0.65 [0.52; 0.73] and 0.89 [0.69; 1.0], p <0.001; according to EQ-5D scale – 64.0 [50.0; 70.0] and 80.0 [70.0; 90.0], p <0.001 ; a PainDETECT score of >12 was found in 24.2 and 2.9% of cases, p< 0.0037; according to HADS, depression ≥11 – in 21.2 and 2.9%, p< 0.001, according to HADS, anxiety ≥11 – in 24.2 and 4.3%, p=0.0038; CSI ≥40 – in 9.0 and 0%, p=0.03; pain catastrophizing ≥30 – in 12.1 and 0%, p=0.005; FIRST ≥5 – in 6.1 and 0%, p=0.358; FACIT <30 – in 15.2 and 2.9%, p=0.004. After 6 months, statistically significant differences were found between the CPTP group and the control group in all sections of KOOS questionnaire (p <0.001 for all parameters).

Conclusion. Three months after knee injury, 32.0% of patients developed CPTP. All had moderate/severe pain with impaired function and reduced quality of life, one in five patients had symptoms of neuropathic pain, signs of depression and anxiety. Patients with CPTP showed significant changes in all sections of KOOS questionnaire.

Objective: to investigate in a multicentre single-stage study the relationships between hyperuricemia (HU) and clinical, instrumental and laboratory parameters of osteoarthritis (OA).

Material and methods. The study included 200 patients aged 40 to 75 years with a definite diagnosis of knee (KN) OA that met ACR criteria, with stage I–III OA by Kellgren–Lawrence. The mean age of the patients was 55.9±10.3 years and the body mass index (BMI) was 29.4±6.2 kg/m2. An individual chart was completed for each patient, including anthropometric parameters, medical history and clinical examination data, visual analogue scale (VAS) assessment of KN pain, WOMAC, patient's general health assessment (GHA) and information on comorbidities. All patients underwent standard radiography and magnetic resonance imaging (MRI) of the KN (WORMS), dual-energy X-ray absorptiometry of the lumbar spine and femoral neck, and laboratory examination.

Results and discussion. HU was diagnosed in 57 (28.5) patients when the serum uric acid (UA) level was above 360 μmol/L. Patients were divided into two groups according to the presence or absence of HU. The age of the patients in the two groups was comparable, but they differed significantly in terms of disease duration, BMI, waist and hip circumference, which were greater in the HU group (p <0.05). Statistically significant differences were also found in the assessment of the severity of OA course: there were higher pain indices according to VAS, WOMAC total score and its components (pain and functional impairment, FI), GHA in the HU group. On MRI, osteitis was more common in the medial aspect of the tibia (odds ratio 5.75; 95% confidence interval 1.29–25.6; p=0.03). Patients with HU had higher concentrations of CRP, COMP, leptin, insulin, triglycerides and creatinine (p <0.05 for all values).

Spearman correlation analysis confirmed the association between HU and duration and radiological stage of OA, the presence of osteitis in the medial aspect of tibia detected by MRI, pain according to VAS and WOMAC, FI according to WOMAC and GHA (p<0.05).

Conclusion. At high UA levels, pain values according to VAS and WOMAC are higher, GHA is worse, and CRP and COMP levels are elevated. MRI shows more frequent osteitis in the medial aspect of the tibia in patients with HU. Deciphering the mechanisms that determine the relationship between HU and OA is important for the development of new methods for the prevention and treatment of these diseases.

Objective: to find approaches to improve diagnostics of the debut of rheumatic manifestations, associated with COVID-19.

Material and methods. Data from 1000 patients from the COVID-19 registry were included in the prospective cohort study. In all patients, the diagnosis of COVID-19 was confirmed by polymerase chain reaction. Of these patients, 380 (41.8% men and 58.2% women, mean age 47.0±2.5 years) had rheumatic manifestations. Patients were examined using routine clinical methods. Immunological markers of rheumatic diseases were determined, including antibodies against cyclic citrullinated peptide, rheumatoid factor, antiphospholipid antibodies and antinuclear factor (ANF), and an immunoblot for antinuclear antibodies was performed if ANF titer was >1:160.

Results and discussion. Patients had the following rheumatic manifestations: arthralgias (in 342), myalgias (in 23), skin rashes (in 15). ANF titers >1:160 were found in 57.6% of patients. No reliable data indicating the development of an antiphospholipid syndrome were found in the study group. Lupus anticoagulant was detected in 5.7% of cases, antibodies against β2-glycoprotein in 5.7%, antibodies against cardiolipin in 3.8%. High ANF titers were found in 63.9% of patients with arthralgia. Gender-specific differences were found when analyzing the correlation between ANF titers and rheumatic manifestations: in men, high ANF tires were associated with myalgias, and in women with arthralgias. The presence of rheumatic manifestations depended directly on the severity of the disease. A correlation between arthralgia and leucopenia was also found – leucocyte count < 3,9 ‧109 /L was a predictor of arthralgias. The sensitivity and specificity of the model were 99.3 and 91.2%, respectively.

Conclusion. The results suggest that COVID-19 can provoke the development of immunological abnormalities that may subsequently lead to the development of an autoimmune diseases (AID). The optimal approach to prevention and early detection of AID in patients with coronavirus infection caused by SARS-CoV-2 is to monitor laboratory parameters – leukocyte count and CRP level. If rheumatic manifestations are present, the use of immunological and imaging examinations is also recommended.

Objective: to analyze the extent of analgesic effect and to determine predictors of inadequate response to local therapy with non-steroidal antiinflammatory drugs (NSAIDs) in a prospective, comparative, randomized trial of the efficacy and safety of Artoxan® gel 1% versus Diclofenac gel 1% in patients with knee OA.

Material and methods. The study included 60 patients with a definite diagnosis of stage II–III Kеllgren–Lawrence knee OA who fulfilled ACR criteria and were observed on an outpatient basis in V.A. Nasonova Research Institute of Rheumatology. Patients were 40–80 years old (mean 62.50±8.04 years), body mass index (BMI) 24.9±4.67 kg/m² , median OA duration 5.7 [3;15] years. According to the randomization scheme, the patients were divided into two groups. In the 1st group (n=30), local therapy with 1% Artoxan gel was applied to the target area of the knee twice daily for 14 days. Patients in the 2nd group (n=30) were prescribed local therapy with the comparator drug, 1% Diclofenac gel with a similar application regimen. Patients in both groups were comparable in terms of the main parameters.

Results and discussion. Patients in both groups showed a significant decrease in pain intensity in the target joint during walking according to the visual analogue scale (VAS) after two weeks of treatment (p <0.05). A decrease in pain (to mild or moderate) in the target joint to <40 mm according to VAS after 7 days of therapy reported 43.3% of patients in the 1st group, and 63.3% of patients after 14 days of therapy (p=0.09). In the 2nd group, 43.3 % of patients also reported a reduction in pain in the target joint to <40 mm according to VAS after 7 days of therapy, and after 14 days it was observed in 56.7% of cases (p=0.22). Although the differences between the groups did not reach statistical significance, a reduction in pain to <40 mm according to VAS and a high BMI (r= -0.28; p=0.029).

Conclusion. The results of the study demonstrate a significant analgesic effect of local NSAIDs in knee OA. In most patients, pain was <40 mm according to VAS after 2 weeks of local NSAID therapy. At the same time, there was a tendency towards a higher frequency of pain reduction to <40 mm according to VAS in the group receiving local therapy with 1% Artoxan gel. It was concluded that excessive body weight and high BMI may be predictors of inadequate analgesic effect in patients with knee OA.

Rituximab (RTM) is a chimeric (murine and human) monoclonal antibody against B-lymphocytes (CD20). RTM is widely used in hematology for lymphoproliferative diseases and in rheumatology for rheumatoid arthritis, Sjögren's disease, some types of vasculitis and systemic connective tissue diseases. The administration of RTM is associated with a depletion of B-cells mediated by the regulation of apoptosis and cytotoxic effects via complement-dependent and antibody-dependent mechanisms. Considering the pathogenesis of autoimmune damage in Graves' disease (GD), an autoimmune thyroid disease associated with thyrotoxicosis, the use of RTM could be effective in this pathology. We present three patients with a combination of diffuse toxic goiter and rheumatic pathology treated with RTM; different outcomes of GD were observed.

Glucocorticoids (GC) and immunosuppressants (IS) are traditional treatments for vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA), often resulting in the development of infections, diabetes mellitus and other adverse events (AEs). The development of a steroid-sparing strategy using biologic disease-modifying antirheumatic drugs (bDMARDs, including rituximab, etc.) and synthetic targeted drugs (avacopan) has radically improved the course of the disease. Currently, there are increasing number of basic and clinical trials of numerous bDMARDs that effectively reduce the number of AEs associated with GC and IS. The steroid-sparing therapeutic strategy not only shows considerable efficacy, but also opens up new perspectives for the treatment of patients with ANCA-associated systemic vasculitis.

The cornerstone of the treatment of gout and hyperuricemia (HU) is the use of urate-lowering drugs, primarily xanthine oxidase inhibitors. Allopurinol, which has been used to treat gout for six decades, is the first line urate-lowering therapy (ULT). However, the principles of ULT prescription, and allopurinol in particular have changed several times. Allopurinol remains the most widely used and highly effective drug in the world for lowering serum uric acid levels, and its prescription in routine clinical practice must fulfil several criteria.
This article outlines the key principles of allopurinol therapy, including indications for use, treatment goals, dosing regimens, evaluation of efficacy, and use in elderly patients and patients with impaired renal function. Adherence to these principles will help prevent treatment failures
in gout and HU.

Impressive successes have been achieved in the fight against viral hepatitis B (HBV), but victory over this infection has not yet been achieved. According to various estimates, there are 6–12.5 times more patients with resolved HBV who are carriers of the virus than carriers of the "Australian" surface antigen HBsAg. The basis for the prevention of HBV is passive and active immunization of the population, but the data on the safety and immunogenicity of this vaccine in patients with rheumatic diseases are contradictory. This review examines the safety and immunogenicity of vaccination against hepatitis B virus (HBV) in patients with immune-inflammatory rheumatic diseases. Vaccination against HBV is indicated for patients at risk of infection and should be carried out before starting antirheumatic therapy, as immunogenicity and efficacy are significantly higher in this case. The necessity of a detailed, targeted medical history collection to clarify the risk of HBV infection before prescribing antirheumatic therapy and clarification of the immune status (presence of HBsAg, antibodies against HBc and HBs) before vaccination is emphasized.

Chronic pain is the main manifestation of rheumatic diseases (RD), it determines the main complaints and worsens the quality of life of patients. The problem of effective control of chronic pain in rheumatology remains a current issue despite the successes in the development of new drugs for pathogenetic therapy, especially in immunoinflammatory RD. For example, 40-50% of patients with rheumatoid arthritis (RA), even those receiving biologic disease-modifying antirheumatic drugs and Janus kinase inhibitors, require analgesics. According to several population studies, about 50% of patients with the most common RD, osteoarthritis (OA) are forced to take various analgesics on a regular basis.

The most popular class of analgesics with proven efficacy in RA, spondyloarthritis (SpA) and OA are non-steroidal anti-inflammatory drugs (NSAIDs). As has been shown in several meta-analyses, NSAIDs are superior to placebo and paracetamol in their therapeutic effect, are not inferior to opioids and are better tolerated overall. However, the use of NSAIDs can be associated with the development of dangerous adverse events (AEs), which requires careful monitoring of the patient's condition, considering comorbid diseases and risk factors. It is very important to choose a drug with a balanced ratio of efficacy and low risk of gastrointestinal and cardiovascular AEs. One such drug is celecoxib, whose therapeutic potential and relative safety have been confirmed in RA, SpA and OA. A differentiated approach to celecoxib prescription makes it possible to achieve a maximum therapeutic result with a minimum risk of AEs. For severe pain, treatment starts with a dose of 400 mg/day, followed by a switch to a maintenance dose of 200 mg/day.

Hyperuricemia (HU) and gout are independent risk factors for chronic kidney disease (CKD). Worldwide, the increasing prevalence of CKD leads to a deterioration in the quality and duration of life of patients and an increase in mortality. If HU plays a significant role in the development of renal failure, then lowering high uric acid (UA) levels should theoretically contribute to the improvement of kidney function. The main method of lowering UA levels is administration of a urate-lowering therapy – xanthine oxidase (XO) inhibitors. The nephroprotective effect of one of the XO inhibitors, febuxostat has been demonstrated in animal models.

The article analyzes the currently available data on the use of febuxostat in patients with HU and gout and different levels of renal function impairment and discusses the possible mechanisms of the drug's nephroprotective effect.

Chronic pain is the main manifestation of musculoskeletal diseases (MSDs), leading to deterioration of quality of life and loss of ability to work. The importance of this problem is determined by the widespread prevalence of MSDs, osteoarthritis (OA), acute and chronic non-specific back pain (NBP), periarticular soft tissues lesions. Introduction of effective methods of treatment of musculoskeletal pain (MSP) into medical practice is one of the fundamental tasks of modern medicine.

The pathogenesis of MSP includes mechanisms such as injury, inflammation, peripheral sensitization, biomechanical disorders, dysfunction of the nociceptive system and psychoemotional disorders. Painful muscle tension plays an important role in the development of MSP, especially in NBP. Given the complex pathogenesis of MSP, its treatment is based on the combined use of drugs with different mechanisms of action and nonpharmacological methods. Non-steroidal anti-inflammatory drugs (NSAIDs) have a central place in this context. However, they can cause serious adverse reactions (ARs), so when choosing NSAIDs, it is necessary to consider comorbid pathology and risk factors. One of the most acceptable NSAIDs with a pronounced analgesic effect and low incidence of ARs is aceclofenac, which is available in various dosage forms (tablets, sachets, topical cream for external use). This medication is characterized by proven efficacy and good tolerability.

Centrally acting muscle relaxants (CM) play an important role in the treatment of MSP. They eliminate muscle spasm, enhance the effect of analgesics and reduce the need for NSAIDs. The effect of CM has been demonstrated in spasticity and NBP. However, the use of many drugs of this group can be associated with serious ARs, which limits their use.

Tolperisone has the best combination of efficacy and favorable safety profile among CM. Its positive effect in the complex treatment of NBP has been confirmed in several well-organized, placebo-controlled trials. There are also studies demonstrating the efficacy of tolperisone in OA. An important advantage of this drug is virtually no sedative effect, and no negative impact on hemodynamics and on the ability to perform concentration-intensive work. Emergence of a new form of tolperisone – extended-release tablets (Mydocalm® Long 450 mg) – increases patient compliance with CM therapy and facilitates the physician's work.