Efficacy and Safety of Levilimab in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: 56-Week Results of Phase III Randomized Double-Blind Placebo-Controlled Trial SOLAR.

. Previously, 24-week results of phase III double-blind, placebo-controlled randomized clinical study (SOLAR) of levilimab in subjects with active rheumatoid arthritis (RA) proved a superiority of levilimab over placebo. Here, we present 1-year efficacy and safety data of the SOLAR study. OBJECTIVES: . To evaluate the efficacy and safety of levilimab in combination with methotrexate (MTX) in subjects with MTX resistant active RA. MATERIALS AND METHODS: : The study was conducted at 21 clinical sites in Russia and Belarus. All randomized subjects have completed the study between November 2019 and October 2021. Adult subjects (154) aged ≥18 years with confirmed diagnosis of RA1 were randomly assigned (2 : 1) to receive either levilimab (162 mg, SC, QW) + MTX (n = 102) or placebo + MTX (n = 52). After W24 of the study all subjects continued to  receive open label levilimab. Subjects who have achieved DAS28-CRP ≤ 2.6 at W24 were switched to maintenance (Q2W) regimen of levilimab at W28 (LVL QW/Q2W and PBO/LVL Q2W arms). Those with DAS28-CRP > 2.6 at W28 continued with QW regimen (LVL QW and PBO/LVL QW arm). The PBO/LVL Q2W arm contained only one subject, thus not included in the analysis. The efficacy analysis was performed in a population of all randomized subjects. Those with missing data due to study discontinuation or rescue therapy prescription were considered non-responders. Otherwise, the analysis was performed on complete cases. Safety was assessed through monitoring of adverse events (AEs) in a population of those, who received at least on dose of LVL (n = 152). RESULTS: : Better response to treatment was observed in LVL QW/Q2W as it composed of those who reach DAS28-CRP ≤ 2.6 at W24. At this time point 15/27 (55.6%) of them achieved ACR70; 23/27 (85.2%) achieved DAS28-CRP remission (<2.6) and 7/27 (25.9%) achieved ACR/EULAR2011 remission of RA. After switching to LVL Q2W, rates of ACR70 and DAS28-CRP<2.6 did not significantly changed until W52: 17/27 (63.0%) and 21/27 (77.8%), respectively, yet the proportion of subject with ACR/EULAR 2011 remission further increased and reached 12/27 (44.4%). LVL QW arm was diminished by subjects who achieved high response to treatment at W24 and composed LVL QW/Q2W arm. Thus, ACR70, and remissions rate in this arm was close to zero at W24. However, continuation of LVL QW in those who not achieved DAS28-CRP ≤ 2.6 at W24 induced ACR70 response in 37/75 (36.0%), DAS28-CRP remission in 35/75 (46.7%) and ACR/EULAR 2011 remission in 8/75 (10.7%) at W52. The most common adverse events (reported in ≥5% of subjects) were blood cholesterol increase (30.3%), ALT increase (23.0%), lymphocyte count decrease (17.1%), ANC decrease (16.4%), blood triglycerides increase (13.8%), bilirubin increase (11.2%), AST increase (9.9%), WBC decrease (9.9%), IGRA with Mycobacterium tuberculosis antigen positive (7.2%), and injection site reactions (5.9%). No deaths occurred. CONCLUSIONS: : Open label period confirmed the lasting efficacy and safety of levilimab in combination with MTX in subjects with MTX resistant active RA and suggested the possibility of switching to levilimab maintenance regimen (once every 2 weeks) (Q2W) in those who achieved remission of RA at week 24.

The Prevalence and Factors Associated with Coronary Heart Disease in Patients with Gout.

Gout is associated with increased risk of cardiovascular disease (CVD) morbidity and mortality. Therefore, an association between coronary heart disease (CHD) and gout deserves careful examination. AIM: . The aim of this study was to determine the prevalence of CHD and factors associated with CHD in patients (pts) with gout. MATERIALS AND METHODS: . The study involved 286 male patients with gout, age 51.2 [42.8; 59.4] years (ys), disease duration 6.2 [3.8; 12.1] ys. All patients underwent standard clinical examination screening traditional risk factors (TRFs) of CVDs. We estimated the adjusted odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: . CHD was found in 111 out of the 286 pts (38.8%), MI had a history in 29.7%. Compared to individuals with CHD, participants without CHD were older (56.7[52.1; 61.1] vs 46.2[40.6; 53.4] ys), had longer duration of gout (9.3[4.7; 15.1] vs 5.6[3.3; 9.7] ys) (for all p < 0.05). Abdominal obesity (OR, 3.6; 95% CI, 1.2-10.9), family history of CHD (OR, 2.2; 95% CI, 1.3-3.7), disease duration of gout more 10 ys (OR, 2.8; 95% CI, 1.6-4.7), age of gout onset < 35 ys (OR, 5.5; 95% CI, 2.6-11.7), intraosseous tophi (OR, 3.03; 95% CI, 1.8-5.01), nephrolithiasis (OR, 1.7; 95% CI, 1.04-3.04), renal failure (OR, 5.6; 95% CI, 2.7-11.4), serum total cholesterol (TC), (OR, 1.6; 95% CI, 1.0-2.8), serum creatinine (OR, 2.5; 95% CI, 1.2-5.1), increased the risk for CHD in patients with a gout. CONCLUSIONS: . The prevalence of CHD was 38.8% among individuals with gout (one-third of patients had a history of MI 29.7%). Our study showed that both TRFs of CVD and the severity of gout and a history of renal failure contribute to the development of CHD in patients with gout.

Clinical Features of ACPA-Negative and ACPA-Positive Variants of Rheumatoid Arthritis.

The aim of the study was to investigate the features of the clinical picture of the disease in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis. MATERIALS AND METHODS: : The study included patients with a reliable diagnosis of rheumatoid arthritis (RA) according to the criteria of ACR/EULAR 2010. Depending on the ACPA values, two groups of patients were recruited: ACPA-positive and ACPA-negative, comparable in gender, age, duration of the disease, and therapy. The nature of the onset and course of the disease and the activity of RA were evaluated (according to the DAS28, SDAI, CDAI indices). RESULTS AND DISCUSSION: : The study involved 79 patients with ACPA-negative variant of RA and 79 ACPA-positive patients. The age of patients (Me [IR] (in years)) with the ACPA(-) variant was 52 [39; 62]; with the ACPA(+) variant, 54 [42; 62]; the duration of the disease (in months) was 59 [23; 122] and 48 [17; 84], respectively. In ACPA(+) patients, a higher disease activity was determined (by the indices DAS 28crp, DAS28esr, SDAI, CDAI), higher values of C-reactive protein and erythrocyte sedimentation rate, and a greater number of painful and swollen joints (p < 0.05). According to the localization of the involved joints, arthritis of the proximal interphalangeal, metacarpal, wrist and shoulder joints was more often determined in ACPA(+) patients. Systemic manifestations of RA at the time of examination and in the anamnesis were statistically significantly more common in ACPA(+) (32.9%) than in ACPA(-) (17.7%) patients. Of the systemic manifestations, rheumatoid nodules were more common in ACPA(+) patients, whereas a tendency to a higher frequency of neuropathy, sclerites, and episcleritis was revealed in ACPA(-) patients. CONCLUSIONS: . In patients with ACPA(-) subtype, clinical signs of joint damage and the inflammatory component are less pronounced compared to ACPA(+). However, the mixed picture of manifestation, the less "bright" course of the disease, the absence of characteristic immunological biomarkers necessitate long-term and careful monitoring of this group of patients. At the same time, the subjective severity of the disease and dysfunction due to ankylosing joints do not differ from the ACPA(+) variant of RA.

Anti-Carbamylated Protein Antibodies in ACPA-Negative and ACPA-Positive Patients with Rheumatoid Arthritis.

The objective of this study was to assess the level of antibodies to carbamylated proteins and analyze the clinical and immunological associations in patients with ACPA-negative and ACPA-positive variants of rheumatoid arthritis. MATERIALS AND METHODS: . The study involved 150 patients with a reliable diagnosis of rheumatoid arthritis and 25 patients as healthy controls. Depending on ACPA values, two groups of patients were recruited: ACPA-positive (n = 75) and ACPA-negative (n = 75). RA activity was assessed by the DAS28 index. Determination of antibodies to carbamylated proteins was performed by enzyme-linked immunosorbent assay (BlueGene Biotech, China). Quantitative determination of ACPA in serum was performed by enzyme immunoassay using a commercial reagent kit (AxisShield, UK; upper limit of normal 5.0 U/mL; Orgentec, Germany; upper limit of normal 20.0 U/mL). RESULTS AND DISCUSSION: . Median anti-CarP in patients with RA was 126.2 [100.83; 157.41] ng/mL and was statistically significantly higher (p < 0.001) than in healthy controls (88.89 [70.53; 107.75] ng/mL). Among all patients with RA, 50 (33.3%) were anti-Carp-positive (22 (29.3%) in the ACPA(+) group and 28 (37.3%) in the ACPA(-) group), and one (2%) volunteer from healthy controls was anti-CarP(+) (p = 0.002). In ROC analysis performed to assess the diagnostic significance of anti-CarP for RA for all patients with RA, the area under the curve was 0.783 ± 0.047 with 95% CI: 0.691-0.874 (p < 0.001), with a cut-off point of 143 ng/mL, specificity 96%, sensitivity 36.7%. In the ACPA(+) RA group, the erosion count was statistically significantly higher (p = 0.044) in anti-CarP(+) patients than in anti-CarP(-) patients. A weak direct correlation between anti-CarP and DAS28 was found in the ACPA(-) RA group. CONCLUSIONS: . We studied the predictive value of anti-CarP as an auxiliary biomarker in ACPA(+) and ACPA(-) subtypes of RA. ACPA(+) anti-CarP(+) patients have a more "erosive" subtype of the disease than ACPA(+) anti-CarP(-) patients. In ACPA(-) patients, anti-CarP helps to identify a more erosive subtype of the disease, and among ACPA(-) patients it helps to reduce the proportion of seronegative patients. Further studies are required to determine the optimal standards for the laboratory diagnosis of anti-CarP and to clarify the diagnostic potential of these ABs as part of the differential diagnosis of arthritis in other rheumatic diseases.

Efficacy of Olokizumab against Comorbid Depressive Disorder in Patients with Rheumatoid Arthritis: Preliminary Results of the Study.

Interleukin (IL) 6 plays an important role in the pathogenesis of depression comorbid with rheumatoid arthritis (RA), and IL-6 inhibitors used to treat patients with RA may have an antidepressant effect. The objective of the study was to evaluate the effectiveness of Russian iIL-6 olokizumab (OKZ) in reducing symptoms of depression in patients with moderate/high RA activity. To date, 49 RA patients have been included, of which 43 (87.7%) are women, with an average age of 47.8 ± 12.8 years; with a predominant high activity of RA according to DAS28 (CRP) indices (89.8%), SDAI (79.6%) and CDAI (75.5%) and inefficacy of stable 12-week therapy with сDMARDs. In all patients, a psychiatrist, in accordance with ICD-10, diagnosed depression (chronic or recurrent) of varying severity during a semi-structured interview. At week 0, all patients were randomized by the method of sequential numbers in a ratio of 1 : 1 : 1 to one of the three study groups: group 1-cDMARDs + OKZ 64 mg subcutaneously once every 4 weeks (n = 18); group 2-cDMARDs + OKZ 64 mg subcutaneously once every 4 weeks + psychopharmacotherapy (PPT) (n = 26); group 3-cDMARDs + PPT (n = 5). The duration of the study is 24 weeks. The dynamics of depression severity was assessed on the PHQ-9, MADRS scales; anxiety, on HAM-A; experimental psychological projective techniques were also used. After 12 and 24 weeks of therapy, there was a significant decrease in the severity of depression and anxiety in all groups of patients. However, the difference between the final and initial values of all scales was statistically significantly greater (p <0.05) in the groups of patients receiving PPT: cDMARDs + OKZ + PPT (ΔPHQ-9 24-0 = -6.75 ± 3.91; ΔMADRS 24-0 = -22.5 ± 4.83; ΔHAM-A 24-0 = -14.6 ± 5.37) and cDMARDs + PPT (ΔPHQ-9 24-0 = -15.5 ± 3.53; ΔMADRS 24-0 = -25.0 ± 1.41; ΔHAM-A 24-0 = -18.5 ± 3.53), compared with the cDMARDs + OKZ group (ΔPHQ-9 24-0 = -4.00 ± 3.89; ΔMADRS 24-0 = -5.75 ± 8.29; ΔHAM-A 24-0 = -8.50 ± 8.21). According to a semi-structured interview with a psychiatrist and design experimental psychological techniques, the proportion of patients without depression after 24 weeks of therapy was significantly higher in the groups of patients receiving PPT: 90% in the group of cDMARDs + OKZ + PPT and 100%-cDMARDs + PPT, as opposed to 25% in the group of cDMARDs + OKZ. OKZ therapy contributed to the normalization of night sleep but did not lead to a decrease in the frequency and severity of cognitive disorders (CDs). OKZ has an antidepressant effect, leads to a decrease in the frequency of sleep disorders. However, a complete regression of depression symptoms when OKZ is prescribed without PPT is possible only in 25% of RA patients, mainly in the patients with mild depression. A combination of OKZ and PPT is optimal for the complete regression of depression and anxiety and a decrease in the frequency and severity of CDs.

The Use of "Acellbia"-A Biosimilar of Rituximab in Systemic Sclerosis.

The possibilities of modern therapy for systemic sclerosis (SSc) remains limited, since most of the used drugs do not have a disease-modifying effect. This encourages the study of new approaches that potentially affect the fundamental pathological processes underlying the disease. One example is anti-B-cell therapy, in particular rituximab (RTX). Until now RTX does not have a registration for the treatment of SSc, but there is a large positive experience of its use, which is reflected in recent meta-analyses and clinical recommendations. Complicated and expensive methods for obtaining genetically engineered biological drugs (biologics) have contributed to the emergence of more accessible biosimilars, one of which is the RTX biosimilar, Acellbia (Biocad, Russian Federation). The ''biosimilar'' versions of RTX might reduce the cost of therapy and increase patients accessibility to this treatment option. The RTX biosimilar Acellbia (ACB) has received approval in Russian Federation in 2014 for all indications held by reference RTX (including rheumatoid arthritis and ANCA-associated vasculitis).

Clinical Significance of Antibodies to DFS70 in Immunoinflammatory Rheumatic Diseases.

The relevance of the problem of immunoinflammatory rheumatic diseases (IIRD) for modern medicine is determined by their high prevalence in the population, the difficulty of early diagnosis, the rapid development of disability and poor life prognosis. Recent data on the significance of anti-DFS70 have opened up new possibilities for optimizing the step-by-step diagnosis of IIRD. The detection of these antibodies can help in the interpretation of a positive result for antinuclear antibodies (ANA) by indirect immunofluorescence assay on HEp-2 cells (IIFA-HEp-2) in the absence of autoantibodies specific for IIRD. Detection of anti-DFS70 in antinuclear factor (ANF) seropositive patients without clinical and/or serological markers characteristic of a certain disease from the IIRD group can be considered as a potential marker that excludes this group of diseases.

[Clinical and instrumental characteristics of psoriatic arthritis in men and women. Data from a cohort observational study].

AIM: To study and compare the clinical and imaging characteristics of psoriatic arthritis (PsA) in men and women. MATERIALS AND METHODS: The study included 956 PsA patients observed in the Russian register, 411 (43%) men and 545 (57%) women. The average age of men/women was 46.0±16.50/50.7±17.20 years (p<0.001), the duration of PsA was 9.9±6.4/10.3±7.6 years (p>0.05), the age at the time of PsA establishment was 37.1±12.30/41.8±13.5 years (p<0.001). Rheumatological examination, X-ray of the pelvis, hands, feet were performed, the LEI, plantar fascia tenderness, body surface area (BSA), body mass index (BMI), CRP, HLA-B27 were determined. Patients filled out assessment scales of pain (Pain), disease activity (patient global assessment of disease activity - PGA), questionnaires HAQ-DI. The indices of Disease Activity in PSoriatic Arthritis (DAPSA), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), criteria of minimal disease activity (MDA) were evaluated. RESULTS: The following differences in the course of PsA in men/women were revealed: X-ray sacroiliitis was detected in 175 (42.6%)/153 (28.1%); p<0.001; the presence of erosions of the joints of the hands and feet - 138 (33.6%)/170 (31.2%); p=0.435; LEI≥3 - 34 (11.4%)/78 (20.9%); p=0.001; Pain - at 48.5±22.60/51.5±22.80 mm VAS; p=0.043; PGA - 50.2±23.07/54.0±21.91 mm VAS; p=0.010; moderate and severe functional disorders (HAQ-DI) were more often observed in women (p=0.002 and p<0.001, respectively); the average value of DAPSA is 26.4±16.8/31.9±22.58; p<0.001; average BASDAI value: 2.7±2.83/1.8±2.78; p<0.001; MDA was achieved in 13 (3.2%)/22 (4.1%); p=0.486; BSA>10% - 54 (13.1%)/102 (18.7%); p=0.021; comorbid diseases - 154 (37%)/277 (51%); p<0.001. At the time of inclusion in the register, the proportion of patients receiving biologic disease-modifying anti-rheumatic drugs was higher in the group of men. CONCLUSION: Our data, based on a large cohort study, demonstrate that PsA debuts in women at a later age than in men, the course of the disease is characterized by higher activity of peripheral arthritis, more pronounced functional disorders and a high prevalence of comorbid diseases. This creates a heavier burden of PsA in women and indicates that gender is an important characteristic of the patient that should be used to predict the course, therapeutic response and progression of the disease.

[NETosis in lupus nephritis].

AIM: To evaluate the levels of MPO-DNA complex in patients with systemic lupus erythematosus (SLE) and its association with the presence of lupus nephritis (LN). MATERIALS AND METHODS: The study included 77 patients with SLE, of whom 30 had SLE without anti phospholipid syndrome (APS), 47 had SLE with APS, and 20 were healthy individuals serving as the control group. The MPO-DNA complex in the serum was investigated using ELISA. RESULTS: The levels of MPO-DNA complex in serum were significantly higher in patients with SLE compared to healthy controls (p=0.001). Among the patients with SLE, 30 (39%) had elevated levels of MPO-DNA complex. The presence of elevated MPO-DNA complex was significantly associated with the presence of a history of LN (p=0.009). Moreover, among the patients included in the study, 20 had active LN, and patients with elevated MPO-DNA complex levels were more likely to have active LN than patients without elevated MPO-DNA complex concentrations [12 (40%) of 30 vs 8 (17%) of 47, χ2=5.029; p=0.034]. An association was found between elevated levels of MPO-DNA complex and the presence of proteinuria, hematuria, cellular hematic/granular casts and aseptic leukocyturia. A direct correlation of MPO-DNA complex with SLEDAI-R was found in patients with active LN (rs=0.497; p=0.026). CONCLUSION: Elevated levels of MPO-DNA complex were detected in 39% of patients with SLE. These patients had a higher prevalence of LN in their medical history and at the time of inclusion in the study. The correlation between MPO-DNA complex levels and the activity of LN according to SLEDAI-R indicates the potential role of MPO-DNA complex as a biomarker for assessing the activity of renal damage in SLE.

[Uric acid, cognitive disorders, neurodegeneration].

This article examines the role of uric acid (UA) in cognitive changes and neurodegeneration, focusing on its functions as an antioxidant and prooxidant. Research suggests that changes in serum UA levels may be associated with the development or delay of cognitive impairment, especially in the context of neurodegenerative diseases such as Alzheimer's disease. It was revealed that there is a relationship between the level of UA and the dynamics of cognitive functions, indicating the potential neuroprotective properties of UA. Particular attention is paid to the balance between the antioxidant and prooxidant properties of UA, which may play a key role in protecting neurons from damage. However, research results are not clear-cut, highlighting the need for further research to more fully understand the role of UA in cognitive processes. Determining the optimal serum UA level may be an important step in developing strategies for the prevention and treatment of cognitive impairment associated with neurodegeneration. Overall, these studies advance the understanding of the mechanisms underlying the interaction between uric acid metabolism and brain health.

[The effect of hypothyroidism on cardiovascular events and type 2 diabetes mellitus developing in rheumatoid arthritis].

AIM: To compare the frequency of cardiovascular events (CVE), to assess the risk of cardiovascular death using the mSCORE and the development of type 2 diabetes mellitus (DM) using the FINDRISC in patients with rheumatoid arthritis (RA) with and without hypothyroidism. MATERIALS AND METHODS: The study included 149 patients (125 women, 24 men) with RA (median age - 57 [52; 61] years). In all patients, traditional factors of cardiovascular risk and glucose metabolism disorders (age, smoking status, total blood cholesterol, blood pressure, overweight, abdominal obesity - AO, heredity burdened by diabetes, insufficient physical activity, the lack of the necessary amount of berries, fruits and vegetables in the daily diet, history of hyperglycemia episodes), the 10-year risk of death from cardiovascular causes according to the mSCORE and the risk of developing type 2 DM according to the FINDRISС were assessed, a history of CVE (myocardial infarctions, and its revascularization, stroke) was recorded. RESULTS: Hypothyroidism was diagnosed in 17.4% of RA patients. Patients with hypothyroidism (group 1) were more likely to have AO and less likely to consume unsufficient dietary fiber than patients with euthyroidism (group 2). Moderate, high and very high risk of development according to the mSCORE and FINDRISC was detected in 61.5% of hypothyroid patients and 48.8% euthyroid patients, according to mSCORE alone - in 30.8 and 44.7%, according to FINDRISC - in 0 and 2.4%, respectively (p>0.05 in all cases); 11.5% of patients in group 1 and 6.5% in group 2 suffered from CVE (OR 1.875, 95% CI 0.462-7.607; p=0.63). CONCLUSION: It is necessary to evaluate the thyroid gland function, especially in patients with AO due to the high frequency of hypothyroidism in RA. Hypothyroidism did not have an independent effect on the severe CVЕ rates, as well as risk assessment according to the score and FINDRISC in RA patients. Theses, with and without hypothyroidism, were predominantly in the moderate, high, very high risk groups according to both scales.

[Autoimmunity in rheumatology: A review].

Autoimmunity and autoinflammation, co-potentiating pathological processes, are considered within the "immune-inflammatory" continuum (continuity with a variety of elements), reflecting the close relationship between the innate and acquired immune responses. Autoimmunity is the leading pathogenetic mechanism for a specific type of human chronic inflammatory disorders - autoimmune diseases, affecting more than 10% of people in the general population. Advances in molecular biology, pharmacogenetics, and bioinformatics provided the background for individualizing therapy for systemic autoimmune rheumatic diseases within personalized medicine. Studying the immunopathogenesis mechanisms, improving diagnostics, interpreting the molecular taxonomy, and developing approaches to the prevention and personalized therapy of systemic autoimmune rheumatic diseases are the priority issues of modern medicine.

[Systemic lupus erythematosus and antiphospholipid syndrome: past, present, future].

Immune-inflammatory (autoimmune and autoinflammatory) rheumatic diseases are widespread severe chronic inflammatory diseases and also "models" for studying the fundamental mechanisms of pathogenesis and approach to pharmacotherapy of other diseases associated with autoimmunity and/or autoinflammation. Uncontrolled inflammation leading to hypercoagulation forms the basis of "thromboinflammation", which is considered a universal pathogenetic mechanism of organ involvement in immune-inflammatory rheumatic diseases, as well as in COVID-19 and atherosclerotic vascular lesions (atherothrombosis). Thrombo-inflammatory mechanisms play a crucial role in systemic lupus erythematosus and antiphospholipid syndrome. Russian rheumatology, under the leadership of academician Valentina Alexandrovna Nasonova, greatly contributed to the research of these disorders. This article addresses the current view about the overlapping pathogenetic mechanisms of thrombosis in systemic lupus erythematosus and antiphospholipid syndrome, the relevance of these studies during the COVID-19 pandemic, and the prospects for antithrombotic and anti-inflammatory therapy.

[Subclinical atherosclerosis of the carotid arteries in patients with rheumatoid arthritis with low cardiovascular risk].

AIM: To evaluate the detection rate of subclinical carotid atherosclerosis in rheumatoid arthritis (RA) patients with low cardiovascular risk (CVR). MATERIALS AND METHODS: The study included 182 RA patients with low CVR (mSCORE<1%) and no established cardiovascular diseases and a control group comprising 100 people. Atherosclerotic lesion of the carotid arteries was assessed using Doppler ultrasound of the carotid arteries and was determined by the detection of atherosclerotic plaque (ASP) - the local increase in the thickness of the intima-media complex (IMT) >1.5 mm. RESULTS: Carotid ASP were observed more frequently in RA patients with low CVR than in the control group (17% versus 8%; p=0.02). The frequency of ASP in RA patients with low CVR did not depend on the disease's stage or activity and ongoing therapy. In RA, the detection of subclinical atherosclerosis was associated with traditional risk factors: carotid ASP were detected 4 times more often in men than in women (48% versus 12%, p<0.01); carotid IMT correlated with age (R=0.46), body mass index (R=0.17), LDL-C level (R=0.20), systolic blood pressure (R=0.17); p<0.05 in all cases. According to a multivariate model, in RA, the risk of developing ASP increased in the presence of dyslipidemia (odds ratio - OR 2.97; 95% confidence interval - CI 1.36-6.49; p=0.006) and arterial hypertension (OR 2.16; 95% CI 1.03-4.54; p=0.04). In RA patients with carotid ASP, sCD40L level was associated with carotid IMT (R=0.32; p=0.04) and cholesterol concentration (R=0.39; p=0.01). CONCLUSION: Subclinical atherosclerotic lesions of the carotid arteries were observed in 24% of RA patients with low cardiovascular risk and were detected almost 2 times more often than in the control group. In RA patients with low CVR, the risk of developing carotid ASP increased by 2-3 times with concomitant hypertension and dyslipidemia. The carotid IMT was associated with traditional risk factors - age, gender, lipid levels and blood pressure indicators, in cases of detection of ASP - with an immunoinflammatory marker - sCD40L.

[Comparative assessment of sensitivity and specificity of three variants of classification criteria for systemic lupus erythematosus in a cohort of Russian patients].

BACKGROUND: The clinical and serologic heterogeneity of systemic lupus erythematosus (SLE) presents challenges for diagnosis, particularly in the earliest stages of the disease when there are insufficient signs to make a reliable diagnosis. AIM: To make a comparative assessment of sensitivity and specificity of various classification criteria of SLE on a cohort of patients of Nasonova Research Institute of Rheumatology. MATERIALS AND METHODS: A total of 252 patients were included in the study; 152 (60%) of 252 patients had reliable SLE (mean age 36 [29.5-46] years, duration of disease 9 [3.4-19] years). Of 252 patients, 26 (11%) had PAPS (mean age 36.5 [31-42] years, duration of disease 4.6 [1-10.4] years). Systemic sclerosis was diagnosed in 74/252 (29%) patients, (mean age 51.5 [42-59] years, duration of disease 9 [5-16] years). The quality of the classification function of the criteria was assessed by ROC analysis. RESULTS: SLE was diagnosed in 131 (86%) of 152 patients using the American College of Rheumatology - ACR)-1997 criteria, in 145 (95%) using the The Systemic Lupus International Collaborating Clinics (SLICC) 2012 criteria, and in 144 (94.7%) using the European League Against Rheumatism (EULAR)/ACR 2019 criteria. ANF positivity was the least statistically significant of all signs in relation to the diagnosis of SLE. The area under the curve (AUC) for ANF≥1/160 titers was AUC 0.654 for the ACR-97 criteria, AUC 0.616 for the SLICC-12 SLE criteria, and AUC 0.609 for the 2019 EULAR/ACR criteria. ROC analysis of the relationship between the number of criteria/points and a reliable diagnosis of SLE revealed a high diagnostic accuracy - the AUC for all SLE criteria was greater than 0.940. In the ROC analysis of patients with SLE and PAFS, indicating the number of diagnostic criteria, sensitivity was 86% for ACR-1997, 95% for SLICC-2012, 95% for EULAR/ACR 2019, and specificity was 100, 62 and 62%, respectively. CONCLUSION: The classification criteria SLICC-2012 and EULAR/ACR 2019 are more sensitive for the diagnosis of SLE in the Russian population, and the criteria ACR-1997 are more specific. All three variants of the SLE classification criteria have sufficient sensitivity and specificity for their use in real clinical practice.

[A new integral enthesial-comorbididity index of psoriatic arthritis activity].

AIM: To develop an integral index of psoriatic arthritis (PsA) activity. MATERIALS AND METHODS: 117 patients with PsA (M/F - 63/54) were included. Patients' age 44±11 years, psoriasis (Ps) duration - 213±153 months, PsA duration - 73.4±78.5 months. Patients underwent standard clinical examination of PsA activity: tender (out of 68) and swollen (out of 66) joint counts (TJC, SJC), LEI, tenderness of the plantar fascia (PF), skin lesion severity (BSA), presence of nail Ps, body mass index (BMI), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), DAPSA, FACIT-F. Parametric and nonparametric statistic methods, correlation and ROC analysis were used. RESULTS: Mean DAPSA was 38±21, TJC - 14.2±10.6, SJC - 10.6±8.3, ESR - 30.5±29.5 mm/h, CRP - 23.3±29 mg/l, LEI - 1.2±1.5, FACIT-F - 32±11, BMI - 27.4±6.2 kg/m2. The following significant positive correlations were revealed: between DAPSA and BMI, patients' age, ESR, PsA and Ps duration, TJC, SJC, LEI, presence of PF enthesitis, skin lesion severity, presence of nail Ps. A negative correlation between FACIT-F and male sex was found. Based on the predictive model of parameters, the Entesial-Comorbid Index of PsA (ECIPsA) was created: 3.81×LEI+13.72×PF+0.54×Age-0.25×FACIT-F+7.36×BSA+7.94×PsA duration+5.5×Nail Ps+0.32×BMI-3.52, namely LEI - Leeds Enthesial Index; PF - pain in the PF; patient's age; FACIT-F - fatigue scale; BSA<3%=0, ≥3%=1; PsA duration≤2 years=0, >2 years=1; presence of nail Ps=1, absence=0; ECIPsA≥28 corresponds with high PsA activity according to DAPSA≥28. ROC analysis of sensitivity and specificity of the prognostic model demonstrated high correctness of the index: the area under the ROC curve was 0.768, 95% confidence interval (0.624-0.913). CONCLUSION: The new PsA activity index corresponds to the existing ones and takes into consideration the clinical heterogeneity and comorbidity of the disease.

[Hypogonadism syndrome in men with inflammatory joint diseases: A review].

Most rheumatic diseases are characterized by sexual dimorphism both in prevalence and in the characteristics of the clinical course. Increased production of pro-inflammatory cytokines that accompanies inflammatory joint diseases may be accompanied by a decrease in the level of male sex hormones, and vice versa, the presence of hypogonadism in men increases the risk of developing certain rheumatic diseases. The review presents data on the relationship between testosterone deficiency and major inflammatory joint diseases, as well as the effect of testosterone replacement therapy on their manifestations.

Different Clinical Relevance of Anti-Citrullinated Protein Antibodies in RA Patients.

The objective of the study was to find a potential relationship between ACPAs and disease activity, bone destruction, and ACPA responses to various therapeutic regimens. The study included 232 patients with rheumatoid arthritis (RA); 90 patients had early RA, and 142 patients had an advanced stage of the disease. 77 (85.6%) patients with early RA were highly positive for anti-CCP, and 29 (70.7%) patients were highly positive for anti-MCV. A positive correlation was found between anti-MCV and DAS28 (r = 0.4; p = 0.04). As for advanced RA, 78 (80.4%) patients were high-positive for anti-CCP, and 70 (79.5%) were high-positive for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r = 0.4; p = 0.02), as well as CDAI (r = 0.4; p = 0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0-122.0)) were found in pts highl-positive for anti-MCV (n = 79), compared to low-positive/negative (n = 27) patients (57.0 (31.0-88.0); p < 0.05). Anti-MCV levels dropped significantly in pts on rituximab and tocilizumab therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment. Anti-MCV levels correlated with inflammatory activity and development of bone destruction and decreased in pts on treatment. Anti-CCP was less responsive and showed minor changes during treatment; therefore, its thorough monitoring was not feasible.

Are the Goals of Therapy Achievable in Patients with Rheumatoid Arthritis Receiving Upadacitinib in Real Clinical Practice?

The aim of the study was to evaluate the effectiveness of UPA in RA patients in real clinical practice after 3 and 6 months of therapy. The study included 63 RA patients with high activity of the disease. Activity was assessed according to the DAS28(ESR), DAS28(CRP), SDAI, CDAI; functional ability to HAQ; quality of life to the EQ-5D; disease activity according to the patient's RAPID-3 index; the level of depression and anxiety to the HADS scale. The effectiveness of therapy was evaluated after 3 (n = 45) and 6 (n = 31) months of UPA therapy. Remission or low activity of the disease by 3 months of therapy was achieved by most patients: remission of 69.8% of patients, low activity of the disease-16.3% of patients. Moderate or high activity persisted in 13.9% of patients. By the 6th month of UPA therapy, the number of remissions reached 90%, low activity 3.3%, moderate activity persisted in 6.7% of patients, high activity of the disease was not in any patient. 20% improvement in function was achieved in 71.8% of patients by the 3rd month of therapy and in 77.8% by the 6th month of treatment; the difference in average HAQ values by the 3rd month of therapy was 0.38 points, by the 6th month-0.58 points. After 3 months of follow-up, 31.1% of patients continued taking GC, by 6 months-24.2%. The dose of GC was reduced from an average of 7.23 to 5.6 mg/s. The percentage of patients requiring NSAIDs decreased from 95.2 to 35.6% and 33.3%, respectively. DMARDs continued to be received by 75.6% of patients by 3 months and 69.7% by 6 months of follow-up. Achieving remission or low activity of the disease in patients with RA receiving UPA in real clinical practice is possible in most patients. A rapid decrease in inflammatory activity is accompanied by a significant improvement in the functional state and quality of life of patients. UPA therapy reduces the need for the use of NSAIDs and reduces the dose of GC in a third of patients.

Contributing Factors of Diabetes Mellitus among Patients with Gout (Results of the Long-Term Prospective Study).

It is assumed that the risk of developing type 2 diabetes mellitus (T2DM) in patients with gout is influenced by both generally accepted risk factors and factors related to gout. The aim of the study was to evaluate the impact of various risk factors for T2DM in patients with gout. A total of 444 patients (49 women, 395 men) ≥18 years old with gout and without DM were included. The duration of observation was 5.66 [2.69; 7.64] years. To identify the factors associated with the risk of developing T2DM, multivariate logistic regression was used, which included sex; T2DM in relatives; insufficient physical activity; unbalanced diet; age  ≥ 45 years; ≥4 attacks per year; presence of tophi; BMI ≥30 kg/m2; allopurinol, febuxostat, glucocorticoids, diuretics, metformin, colchicine; GFR < 60 mL/min/1.73 m2; serum uric acid level (sUA) ≥ 420 µmol/L and  ≥ 480 µmol/L. T2DM developed in 108 (24.3%) patients. According to the multivariate model, the presence of ≥4 attacks of arthritis per year increased the risk of T2DM (OR = 5.23; 95% CI: 2.98-9.19; p = 0.0001); presence of tophi (OR = 2.61; 95% CI: 1.50-4.54; p = 0.001); sUA ≥ 480 µmol/L (OR = 2.26; 95% CI: 1.02-5.00; p = 0.144); diuretics (OR = 2.35; 95% CI: 1.19-4.64; p = 0.014). Febuxostat (OR = 0.31; 95% CI: 0.11-0.84; p = 0.022) and metformin (OR = 0.49; 95% CI: 0.21-1.16; p = 0.107) reduced the risk of developing T2DM. Risk of T2DM in patients with gout is associated with high incidence of arthritis attacks, MK ≥ 480 µmol/L, hypertension, diuretic use, and febuxostat and metformin reduces risk.