Evgeniy Vasilievich Papichev

Scopus Publications

Analysis of the relationship between the composite body composition and the serum level of fibroblast growth factor 21 in female patients with rheumatoid arthritis

Association of serum chemerin levels with complications and comorbidity in rheumatoid arthritis
E. V. Papichev, Yu. R. Akhverdyan, Yu. V. Polyakova, L. E. Sivordova, and B. V. Zavodovsky
Remedium, Ltd.
Introduction. Rheumatoid arthritis (RA) is a systemic autoimmune disease as well as a typical inflammatory process. Chemerin is a fat tissue cytokine, which specific receptors were discovered on the surface of the innate immune cells. It is of interest to study the association of chemerin with the complications and comorbidity in RA.Aim. To study the association between serum chemerin levels with complications and comorbidity in rheumatoid arthritis.Materials and methods. 88 women with RA were enrolled in our study. ll patients undergone standard clinical and laboratory examination. Serum chemerin, high-sensitive C-reactive protein (hsCRP), anti-citrullinated protein antibodies, insulin and C-peptide levels were determined using ELISA. X-ray absorptiometry was performed. Statistical analysis was performed using conventional methods with a software package Statistica 10.0.Results. Median chemerin concentration was 463.5 [366–576.5] ng/ml. Chemerin concentration correlated with the age (ρ = 0.232; р = 0.030), weight (ρ = 0.254; р = 0.017) and body mass index (BMI) (ρ = 0.212; р = 0.047), but wasn’t associated with the RA classification criteria. Positive correlation between chemerin concentration and number of painful joints (NPJ) (ρ = 0.213; р = 0.046) and hsCRP (ρ = 0.273; р = 0.010) was observed. Patients with type 2 diabetes mellitus (DM2) had higher chemerin concentration (598.0 ng/ml vs 479.5 ng/ml, Z = -2.68; p = 0.007) and patients with cholecystectomy in anamesis had lower (359.0 ng/ml vs 479.0 ng/ml, Z = 2.02; p = 0.043). Chemerin concentration correlated with systolic and diastolic blood pressure (BP) (ρ = -0.41; р < 0.001 and ρ = -0.27; р = 0.028, respectively).Conclusions. Chemerin concentration in women with RA correlates with age, weight, BMI, NPJ and hsCRP. Chemerin concentration in patients with comorbid DM2 was higher and in patients comorbid with cholecystectomy in anamnesis was lower. Chemerin concentration correlates negatively with a systolic and diastolic BP.

Assessment of the quality of life of patients with gonarthrosis treated with a prosthesis of synovial fluid of domestic production
L. E. Sivordova, Yu. V. Polyakova, E. V. Papichev, Yu. R. Akhverdyan, and B. V. Zavodovskii
Remedium, Ltd.
Introduction. Osteoarthritis (OA) is a chronic progressive disease of the joints, accompanied with pain, which limits the mobility of patients. Functional limitations, chronic pain syndrome worsen the quality of life (QoL) in OA of the joints of the lower extremities. QoL significantly depends on the effectiveness and methods of pain treatment, correction of functional disorders.Aim. Evaluation of the dynamics of QoL in patients with gonarthrosis treated with a high-tech synovial fluid prosthesis – sodium hyaluronate, domestic production.Materials and methods. The study group consisted of 50 patients who received intra-articular (IA) injections of domestically produced sodium hyaluronate (OOO Ingal, Russia). Comparison group – 30 patients treated with 2 ml of symptomatic drugs of delayed action (SYSADOA) (bioactive concentrate of small marine fish) administrated IA No. 5. Control group – 100 patients treated with a 1 ml of SYSADOA drugs administrated intramuscularly (IM) No. 20. Study program: 12 months, 6 visits with prospective monitoring of the quality of life of patients according to SF-36 compared with baseline data.Results. At the time of inclusion, patients had a similar level of physical and mental health components, which did not differ statistically significantly (p = 0.369 and p = 0.089). The study group demonstrated the best dynamics of the physical and mental components of health. The therapy was effective in all groups: most patients showed a statistically significant decrease in pain syndrome, an increase in QoL. The groups differed significantly in the speed of achieving the effect of pain relief, the severity of pain reduction and the duration of the effect of treatment.Conclusions. The spectrum of side effects of non-steroidal anti-inflammatory drugs (NSAIDs) does not allow their use for pain relief indefinitely. SYSADOAs become less effective in the progression of OA than in the early stages of the disease. The positive clinical effect of intra-articular injection of sodium hyaluronate solutions occurs faster and lasts longer than when using SYSADOA.

Advantages of zoledronic acid in the therapy of osteoporosis in real clinical practice
L. E. Sivordova, Yu. V. Polyakova, E. V. Papichev, Yu. R. Akhverdyan, and B. V. Zavodovskii
Remedium, Ltd.
Introduction. The development of osteoporosis (OP) increases healthcare costs and often leads to disability of patients. In this regard, the search for ways to improve the effectiveness of OP treatment is very relevant. Today, there is a wide range of drugs for the effective correction of bone metabolism. However, low patient compliance in real clinical practice significantly reduces the effectiveness of therapy.Aim. To study the effect of patient compliance on the effectiveness of Zoledronic acid and Denosumab in OP in real clinical practice.Materials and methods. Study design: a retrospective analysis of outpatient records of 300 patients with OP, who were prescribed Zoledronic acid or Denosumab in 2019, with a prospective analysis of adherence to therapy for 3 years.Results. It was revealed that 12% of patients did not start pathogenetic therapy for OP (control group). 88% (264 patients) started pathogenetic therapy: of these, 22.33% (67 patients) preferred therapy with Denosumab; 65.67% (197 patients) – Zoledronic acid. After 1 year, therapy with Denosumab 19.4%, Zoledronic acid – 19.29% was discontinued. More than 1 month late with the next injection of the drug: Denosumab – 25.37%, Zoledronic acid – 16.24% of patients. Only 55.22% who received Denosumab and 64.47% who received Zoledronic acid fully complied with the recommendations. Most often, a violation of the schedule of drug administration was observed in patients over 75 years of age, alone, with impaired cognitive status. Discontinuation of therapy with Denosumab or violation of the schedule of its administration led to an increase in the level of bone resorption (C-telopeptide type I collagen (CTX-1)). During therapy with Zoledronic acid, there was no increase in CTX-1. In addition, the cost of course treatment with Zoledronic acid is 2–3 times less than with Denosumab.Conclusion. In real clinical practice, zoledronic acid has clinical and pharmacoeconomic advantages, especially in patients with expected low adherence to OP therapy.

Risk factors for osteoporosis in patients with rheumatoid arthritis
Yu. R. Akhverdyan, E. V. Papichev, B. V. Zavodovsky, J. V. Polyakova, and L. E. Seewordova
Institute of Cytology and Genetics, SB RAS
Aim of the study was to investigate risk factors for osteoporosis (OP) in patients with rheumatoid arthritis (RA). Material and methods. We observed 110 patients with a verified diagnosis of RA. RA was diagnosed based on the 2010 EULAR/ACR clinical classification. All patients with RA were divided into 2 groups: with ОP (53 patients) and without ОP signs (57 patients). Bone mineral density (BMD) was assessed by dual-energy X-ray densitometry (DEXA), the diagnosis was made on the basis of WHO recommendations. All patients underwent a standard clinical and laboratory examination, in addition the following parameters were studied: 25-OH vitamin D, C-terminal telopeptide of type I collagen (CTX-1), N-terminal propeptide of procollagen I (P1NP) content in the blood, the ratio of calcium to urine creatinine. Results. We found a statistically significant relationship between the presence of ОP and the following clinical signs: patient weight (р = 0.014), duration of RA course (р = 0.024), and the presence of erosive changes (р = 0.014). In addition, a relationship was found between the presence of OP and lower BMD in the Ward area (Ward) and the greater trochanter area (Troch) (р < 0.0001). It was also shown that taking glucocorticosteroid drugs for more than 3 months significantly increases the risk of developing ОP (р < 0.0001). Conclusions. Identification of risk groups for patients at risk for the development of OP is of great practical importance. The factors given in the article can be adjusted towards normalization in order to reduce the degree of possible risk, which is quite feasible in practice.

Clinical efficiency and safety of innovative synovial fluid prosthesis in the treatment of gonarthritis
L. E. Sivordova, J. V. Polyakova, E. V. Papichev, Y. R. Akhverdyan, and B. V. Zavodovsky
Remedium, Ltd.
Introduction. Scientific discussions about ways to improve the effectiveness and safety of osteoarthritis (OA) therapy do not stop. The article discusses the most controversial issues of the problem and presents the results of a study on the use of sodium hyaluronate in gonarthrosis.Aim. To compare the clinical efficacy, tolerability and safety of the use of synovial fluid substitute of domestic manufacture and symptomatic slow-acting drugs (SYSADOA) in patients with gonarthrosis. Study design. Prospective, comparative, randomized, single center study. The duration of the study was 12 months.Materials and methods. The study included 180 patients with gonarthrosis, randomized into three groups. Study group: 50 patients treated with Ripart® sodium hyaluronate solution intra-articularly. Comparison group: 30 patients treated with SYSADOA, intraarticular. Control group: 100 patients treated with SYSADOA intramuscularly.Results. The most rapid and pronounced decrease in the VAS index was obtained during sodium hyaluronate therapy: by 31% at the 1st week, by 48% by the end of the 2nd week, with a maximum decrease by 49.1% by the 3rd month (p < 0.001). After 12 months, a lower level of the VAS index was observed: 32% lower than before the start of therapy (t = 47.23; p < 0.001). Comparable results were observed in this group in terms of the dynamics of the AUSCAN/WOMAC index. The effectiveness of therapy in the comparison and control groups was lower (p < 0.05). In addition, the use of sodium hyaluronate provided a significant reduction in the need for taking NSAIDs: 20 patients completely stopped taking NSAIDs (40%), 25 (50%) – they began to take NSAIDs less often or reduced the dose of drugs by 2 times, after 12 months they continued taking NSAIDs only 20% of patients in this group (p < 0.05).Сonclusions. Thus, Ripart® demonstrated high efficiency in reducing pain, contributed to a significant reduction in the need for NSAIDs in patients with gonarthrosis, and has a good safety profile.

Menopause and rheumatoid arthritis as factors associated with osteoporosis development
, E.V. Papichev, J.V. Polyakova, , Yu.R. Akhverdyan, , L.E. Sivordova, , B.V. Zavodovsky, and
Krasnoyarsk State Medical University
The aim of the research. To study the role of menopause, glucocorticoids (GCs) intake and characteristics of rheumatoid arthritis (RA) in development of osteoporosis (OP) and osteoporotic fractures. Material and methods. A total of 73 female RA patients in menopause were examined. The control group included 29 female RA patients in premenopause. In addition to standard clinical and laboratory examinations, P1NP, 25(OH)D, CTX-1 were measured, dual-energy x-ray absorptiometry and x-ray of the thoracic and lumbar spine were performed. Statistical analysis was performed using the “Statistica 12.0” software package. Results. Premenopausal patients had lower BMI. Patients in postmenopause had higher rate of OP (42 patients) than the controls (8 patients) (57.5% vs 27.6%, respectively). Among patients in postmenopause, OP was associated with lower BMI (27.6 vs 30.5 kg/m2), higher cumulative dose of GCs (6.9 vs 1.65 g), higher duration of GCs intake (32 vs 18 months), lower RA activity (3.37 vs 3.9 according to DAS28-CRP) and lower CTX-1 level (0.52 vs 0.7 ng/ml). In the same group, osteoporotic fractures were only associated with longer GCs intake (32 vs 24 months). In premenopause patients, OP was associated with longer RA duration (21 vs 6 months), cumulative dose of GCs (13.9 vs 0.45 g), duration of GCs intake (48 vs 3 months), higher level of hs-CRP (46 vs 8 mg/l) and lower P1NP level (51.8 vs 43.8 ng/ml). Osteoporotic fractures in premenopause were associated with RA duration (28 vs 6 months), cumulative dose of GCs (12.5 vs 1.2 g) and lower BMD in all examined areas. Conclusion. The OP rate was higher in postmenopause patients. In both groups, the duration of GCs intake and accumulated dose of GCs were associated with OP. In postmenopause, OP was also associated with lower BMI. In premenopause, OP and osteoporotic fractures were associated with longer RA duration, cumulative dose of GCs and lower BMD in all studied areas.

Рain syndrome in the shoulder joint. Clinical significance of bioactive concentrate of small seafish in real clinical practice
L. E. Sivordova, Yu. V. Polyakova, E. V. Papichev, Yu. R. Akhverdyan, and B. V. Zavodovskii
Remedium, Ltd.
The limitation of the range of motion of the upper limb in combination with chronic pain syndrome and a decrease in the muscle strength of the arms leads to a significant deterioration in the quality of life of patients, often negatively affects their psychoemotional status, and reduces the ability to work. Arthrosis of the shoulder joint and pathology of the periarticular tissues of the shoulder affect up to 21% of the adult population and up to 33% of people over 60 years of age. Disagreements in the etiology, pathogenesis, terminology, approaches to the diagnosis and treatment of pain syndromes in the shoulder joint area do not contribute to the development of a unified concept of therapy for this pathology. The article provides a review of the literature on the epidemiology and pharmacotherapy of osteoarthritis and soft tissue pathology of the shoulder joint with an analysis of two clinical cases. The peculiarity of the first clinical case is the rapid achievement of therapeutic goals for third grade shoulder osteoarthrosis in an elderly patient with high comorbidity. This allows us to draw conclusions about the predominant role of periarticular tissues inflammation in the generation of severe pain syndrome. The second clinical case presents the dynamics of the development of calcifying tendinitis of the right, later of the left shoulder joint in a woman of working age. The use of a bioactive concentrate of small sea fish (BCSSF) (Alflutop®, Biotechnos) made it possible to quickly reduce the severity of the pain syndrome and return to the usual way of life in the first patient, which made it possible to shorten the use of non-steroidal anti-inflammatory drugs. In the second clinical example, BCSSF promoted the stimulation of regenerative processes in the periarticular tissues of the shoulder joint, the restoration of the function of the dominant limb and the ability to work. Thus, BCSSF may be the drug of choice for patients with osteoarthritis of the shoulder joints with a high risk of cardiovascular and gastrointestinal complications, as well as the drug of choice for a faster recovery of function in case of damage to the periarticular apparatus.

Comparative characteristics of the level of highly sensitive C-reactive protein in patients with systemic lupus erythematosus and rheumatoid arthritis
Yu. R. Akhverdyan, B. V. Zavodovsky, Yu. V. Polyakova, L. E. Seewordova, and E. V. Papichev
Institute of Cytology and Genetics, SB RAS
The aim of this work was to study the dependence of the concentration of C-reactive protein in the blood of patients on the severity of systemic lupus erythematosus (SLE). Material and methods. We examined 26 patients with SLE, the comparison group consisted of patients with rheumatoid arthritis (RA) (n = 88). Results. The hsCRP level was significantly higher in patients with a high degree of activity than in patients with minimal and moderate SLE activity (F = 4.409, p = 0.023). In addition, in patients with SLE, a significant direct correlation was found between hsCRP and ESR values (r = 0.409, p = 0.047), antinuclear factor (r = 0.389, p = 0.021), antibodies to double-stranded DNA (r = 0.226, p = 0.033), leukocytes in urine (r = 0.571, p = 0.002), microalbuminuria (r = 0.727, p = 0.017) AsAT (r = 0.428, p = 0.046), and inverse correlation – with the value of blood leukocytes (r = –0.662, p < 0.001). Conclusion. It was found that an increase in the levels of hsCRP in the sera of SLE patients is accompanied by an increase in the degree of disease activity, which indicates a direct correlation between the level of hsCRP and SLE activity. Consequently, the concentration of hsCRP reflects the acute phase response and the intensity of the inflammatory process in SLE.

Study of risk factors for the osteoporosis development in Rheumatoid arthritis in real clinical practice
E. V. Papichev, Yu. R. Akhverdyan, Yu. V. Polyakova, L. E. Sivordova, and B. V. Zavodovskii
Remedium, Ltd.
Introduction. Osteoporosis is a common complication of rheumatoid arthritis. Its development is associated with the mechanisms underlying in the progression of autoimmune inflammatory diseases and therapeutic approaches used for them. The study of risk factors for osteoporosis can contribute to the clarification of its pathogenesis components, as well as the development of new methods for prevention, diagnosis and treatment of this condition.Aim. To study the role of anamnestic, clinical and laboratory factors for secondary osteoporosis in women with rheumatoid arthritis.Materials and methods. 102 women with rheumatoid arthritis were enrolled in our study. Exclusion criterias were type 2 diabetes mellitus, hepatic cirrhosis, hepatocarcinoma and level of alanine aminotransferase ≥ than 3 upper limit ofnormal. The cumulative dose, duration and daily dose of glucocorticoids (GC) were determined by patient intake. All patients undergone standard clinical and immunological examination. Serum fetuin-A, 25-hydroxycalciferol, C-telopeptide of collagen I type, N-terminal propeptide of collagen I type levels were determined using ELISA. X-ray of afflicted joints and dual-energy x-ray absorptiometry were performed. Statistical analysis was performed using conventional methods. Forced data entry was used to perform multiple logistic regression. Hereinafter data is presented as odds ratio (OR) and 95% confirmation intervals (CI).Results. OR for osteoporosis were higher in women of age ≥ 58.5 years (OR 1,07 (1.02–1.12)), body mass index (BMI) ≤ 27 kg/m2 (OR 1.1 (1.01–1.2)), cumulative dose of GC ≥ 7.6 g (OR 1.09 (1.02–1.17), serum fetuin-A levels ≤ 660 μg/ml (OR 1,05 (1,01–1,09) and if the duration of GC intake is more than 3 months (hereinafter if dose of glucocorticoids is ≥ 5 mg for prednisolone daily) (OR 12.3 (4.12–36.5). Adjusted OR for osteoporosis were higher in women of age ≥ 58.5 years old (adjOR 1.08 (1.01–1.16), serum fetuin-A levels ≤ 660 μg/ml (adjOR 1.08 (1.01–1.15) andif the duration of GC intake is ≥ than 3 months (adjOR 12.1 (1.44–102.3).Conclusions. Women with RA of ≥ than 58.5 years old, duration of GCs intake more than 3 months and serum fetuin-A levels ≤ than 660 μg/ml had higher odds for osteoporosis.These are independent factors for osteoporosis in women with rheumatoid arthritis, whichshould be used in patient’s management.

Clinical significance of collchicine in pharmacotherapy of cardiovascular pathology in patients with hyperuricemia in rheumatic diseases
L. E. Sivordova, J. V. Polyakova, E. V. Papichev, Y. R. Akhverdyan, and B. V. Zavodovskii
Remedium, Ltd.
For a long time, there has been scientific debate about the appropriateness of prescribing drugs to lower the level of uric acid in patients without clinical manifestations of gout. Long-term hyperuricemia is known to be the cause of gout and gouty arthritis. However, an increased level of uric acid is often found in a number of other diseases (metabolic syndrome, kidney disease, cardiovascular disease, psoriasis). Clinical evidence suggests that uric acid-lowering therapy slows the progression of cardiovascular disease and chronic kidney disease. And, if in rheumatological practice this issue still remains a subject of discussion, then the cardiological community by 2019 has clearly defined the indications for starting urate-lowering therapy. The Consensus on the Management of Patients with Hyperuricemia and High Cardiovascular Risk strongly recommends that the practitioner prescribe drugs to control hyperuricemia in hypertensive patients. The need to control the level of uric acid is reflected in the relevant sections of the Clinical Guidelines for the Management of Patients with Arterial Hypertension, 2020. This article provides a review of the literature on the etiology, pathophysiology, pharmacotherapy of hyperuricemia in patients with cardiovascular and rheumatic diseases. A separate section is devoted to scientific studies of the effects of colchicine in advanced therapy for CVD and RD. A clinical case of observation of a patient with newly diagnosed psoriatic arthritis, hyperuricemia, high cardiovascular risk is presented. The peculiarity of this clinical case is the onset of the disease after orthopedic surgery on the knee joints, high comorbidity and poor tolerance of standard basic therapy. The use of colchicine stabilized the patient’s condition. Thus, in clinical practice, it is necessary to take into account the role of hyperuricemia in the pathogenesis of inflammation in cardiovascular pathology. Colchicine may be the drug of choice for patients with hyperuricemia at high cardiovascular risk.

Prediction of osteoporosis severity in patients with rheumatoid arthritis via evaluation of the Fetuin-A level
, Yu.R. Akhverdyan, E.V. Papichev, , B.V. Zavodovsky, , Ju.V. Polyakova, , L.E. Polyakova, and
Krasnoyarsk State Medical University
Aim of study. To investigate the level of dependence of osteoporosis (OP) progression severity on the level of fetuin-A (FA) in order to predict the OP progression severity in RA patients. Material and methods. We have examined a total of 110 RA patients (mean age 54.2+11.97). Th e diagnosis was established based on ACR/EULAR criteria 2010. A total of 30 conventionally healthy subjects were enrolled serving as a control group. Evaluation of bone mineral density (BMD) was performed using DXA (Lunar DPX-NT GE densitometer). The FA level was determined through indirect enzyme-linked immunoassay (Human Fetuin-A ELISA test-system). Results. Mean serum FA in healthy subjects amounted to 653.55-972.19μg/ml. We formed 2 groups of RA patients: with blood serum FA levels <653.55μg/ml (23 patients) and with normal FA values: 653.55μg/ml or higher (87 patients). A lowered FA level was revealed in 20 (86.96 %) subjects in the group of OP patients and only in 3 (13.04 %) patients with RA without OP (р<0.001). Osteoporotic bone fractures were diagnosed in 12 (13.79 %) patients in the group with normal FA levels and were absent in 75 (86.21 %) patients (р<0.001). Apart from that, RA patients with lowered FA had reliably lower mean BMD in the area of femoral neck and vertebral column as well as lower BMD total value (р<0.001). In order to determine the diagnostic accuracy of laboratory tests, the characteristic curve (ROC curve) was applied. Th e area under the ROC-curve was 0.663 with the cut-off point matching the FA level of 660.3μg/ml. Th is value corresponds with 84.72 % specifi city and 47.37 % sensitivity. Conclusion. We have revealed reliable correlations between the serum FA level in RA patients, the frequency of OP development, osteoporotic bone fractures and BMD values (p<0.001). Laboratory evaluation of FA for OP progression severity prediction for RA patients has good quality with the specifi city of 84.72 % and the sensitivity of 47.37 %.

Modern facilities of pharmacological correction of hyperuricemia in rheumatic diseases: Management of difficult clinical cases
L. E. Sivordova, Yu. V. Polyakova, E. V. Papichev, Yu. R. Akhverdyan, and B. V. Zavodovskii
Remedium, Ltd.
The article presents clinical cases of management of patients with low compliance with treatment, suffering from rheumatic diseases and disorders of purine metabolism.Cases report 1. The first patient with advanced gout, after taking 100 mg of allopurinol, developed undesirable effects: sore throat, change in voice, cough, and therefore treatment was discontinued. After six months without therapy, the condition worsened and, in self-medication, the patient resumed taking allopurinol at a dose of 300 mg per day, which, as expected, resulted in a resumption of the allergic reaction and a serious exacerbation of gouty arthritis. In order to stop continuous relapses of arthritis, it became necessary to prescribe glucocorticoids. After stabilization of the state, constant administration of febucostat with positive clinical and laboratory dynamics was recommended.Cases report 2. The second patient with rheumatoid arthritis (RA) developed analgesic nephropathy, secondary hyperuricemia, and typical gouty attacks in the background of high activity of the underlying disease, existing kidney pathology and inappropriate use of non-steroidal anti-inflammatory drugs (NSAIDs). Frequent exacerbations of arthritis prompted the patient to finally see a rheumatologist. The adjusted therapy made it possible to reduce RA activity, reach the recommended level of uric acid, and reduce the drug load on the kidneys with almost complete withdrawal of NSAIDs. Thus, in modern conditions, rheumatologists have in reserve all the necessary means for the pharmacological correction of hyperuricemia, even in difficult clinical cases. Febucostat is the drug of choice for correcting uric acid levels in case of intolerance to allopurinol, as well as in the development of secondary gout against the background of renal failure. In addition, it should be noted that the effectiveness of the treatment of rheumatic diseases largely depends on the patient’s compliance. To increase adherence to therapy, regular patient schools are recommended.

Investigation of clinical and laboratory manifestations of rheumatoid arthritis depending on the level of serum fetuin-a

Body composition and serum fetuin-A levels in patients with rheumatoid arthritis
Б.В. Заводовский, Л.Е. Сивордова, Ю.Р. Ахвердян, Ю. В. Полякова, E. Papichev, B. Zavodovsky, L. Sivordova, Y. Akhverdyan, Y. Polyakova and I. Zborovskaya
Institute of Cytology and Genetics, SB RAS
Background. Rheumatoid cachexia is a pathological condition which appears in patients with rheumatoid investigate the prevalence of rheumatoid cachexia and the association of serum fetuin-A level with body composition absorptiometry with Total Body program was performed. The diagnosis of rheumatoid cachexia was based on the next criteria: fat-free mass index less than 10th percentiles with fat mass index above 25th percentiles. Results and discussion. We observed rheumatoid cachexia in 25 patients (22,7 %). According to the literature, such patients have an increased risk of developing metabolic syndrome, arterial hypertension and mortality. Positive significant ( p < 0,05) correlations were observed between serum fetuin-A levels and right and left lower limb, trunk, gynoid region, both lower limbs and total body bone mass. No statistically significant relationships with other indicators were identified. Fetuin-A negative dynamic in patients with rheumatoid arthritis may be accompanied by the loss of bone mass, which requires the improvement of therapeutic approach. Conclusions. Almost a quarter of patients with rheumatoid arthritis have rheumatic cachexia. Positive correlation between serum fetuin-A levels and lower limbs, trunk, gynoid region and total body bone mass was observed.

Assessment of the safety, tolerability and effectiveness of first Russian generic aceclofenac in patients with undifferentiated peripheral inflammatory arthritis
B. V. Zavodovsky, L. E. Sivordova, Yu. V. Polyakova, Yu. R. Akhverdyan, and E. V. Papichev
Consilium Medicum
Aim. To evaluate the effectiveness and tolerability of the drug in patients with undifferentiated peripheral inflammatory arthritis (UPIA). Materials and methods. We observed 60 patients (39 women and 21 men) met G. Hazlewood et al., UPIA criteria, 2011. Patients were divided into 3 groups: with monoarthritis, oligoarthritis and polyarthritis. They took aceclofenac 100 mg twice day for 3 weeks. Results. We noted significant decreasing in pain level according to visual analogue scale: in patients with monoarthritis by 69.3 mm (p0.001); in oligoarthritis group by 47.5 mm (p0.001), in patients with polyarthritis by 30 mm (p0.001). The life quality by the EQ-5D-5L index was improved too in all groups from 0.616 to 0.829 (p0.001). The satisfaction with the therapy was: in monoarthritis patients (80% of patients and 93% of doctors noted good results), in oligoarthritis group (53% and 39% accordingly) and polyarthritis (74% and 64% respectively). We suppose the difference was due to the fact that mono- and oligoarthritis patients suffered from initial forms of seronegative spondylarthropathy, in which the effectiveness of NSAIDs is traditionally higher; polyarthritis patients probably had debut of rheumatoid arthritis. Adverse events of therapy were mild. We noted gastrointestinal tract symptoms (dyspepsia) and increased ALT in 10 patients and increased blood pressure in 1 patient. The symptoms did not require discontinuation of therapy. Сonclusion. Post-registration observational study of first Russian generic aceclofenac (Alental, Vertex, Russia) was conducted. In UPIA patients aceclofenac therapy was most effective in mono- and oligoarthritis patients. The first Russian generic aceclofenac (Alental, Vertex, Russia) has good efficacy, tolerability and safety and can be recommended for arthritis treatment.

Rheumatoid arthritis in real clinical practice: initiation of therapy with biological agents. Results of the «Computer Terminals of Self-Assessment for Patients with Rheumatic Diseases» («TERMINAL-II») project
V. N. Amirdzhanova, E. Yu. Pogozheva, A. E. Karateev, O. V. Antipova, I. B. Vinogradova, A. Yu. Kazankova, R. G. Mukhina, A. G. Vasilyev, O. B. Nesmeyanova, E. A. Bogdanova,et al.
IMA Press, LLC

FETUIN-A AND SECONDARY OSTEOPOROSIS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Evgeniy V. Papichev, Boris V. Zavodovsky, Larisa E. Seewordova, Yuriy R. Akhverdyan, and Yuliya V. Polyakova
ECO-Vector LLC
Aim. To study the level of fetuin-A (FA), bone mineral density (BMD) and certain markers of bone remodeling in patients with rheumatoid arthritis (RA). Materials and Methods. 110 Patients with RA and 30 conventionally healthy patients were examined. In both groups the levels of FA and BMD were determined. In the group of patients with RA the levels of C-telopeptide of type I collagen, N-terminal propeptide of procollagen I, 25-hydroxy-cholecalciferol, total alkaline phosphatase, total calcium of blood were determined. Results. The mean concentration of FA in blood serum of patients with RA was 765.67±120.66 µg/mL, which was below the respective parameter in donors – 812.95±76.21 µg/mL (p=0.0437). In the group of patients with RA with osteoporosis (n=52) the mean level of FA was 733.65±135.84 µg/mL, and in the group without osteoporosis – 794.37±97.7 µg/mL (p=0.0044). The level of FA was also reduced in patients with osteoporotic fractures (n=24) – 694.79±110.47 µg/mL against 785.45±116.43 µg/mL in patients without osteoporotic fractures (n=86; p=0.00091). A positive correlation relationship was found between the level of FA and BMD of L1-L4 (r=0.194; p=0.042), femoral neck (r=0.328; p<0.0001) and proximal femur (r=0.293; p=0.002), and the level of 25-hydroxy-cholecalciferol (r=0.259; p=0.006), and the negative correlation relationship – with C-telopeptide of type I collagen (r=-0.203; p=0.033). Conclusions. Patients with RA with reduced FA level were characterized by a higher detection rate of osteoporosis and of osteoporotic fractures, and by a lower BMD of L2-L4, femoral bone and proximal femur. Besides, a lower level of FA was associated with a lower level of 25-hydroxy-cholecalciferol and with a higher level of C-telopeptide of type I collagen which permits to suggest existence of osteoprotective function in this glycoprotein.

Serum fetuin-A levels in patients with rheumatoid arthritis
E. V. Papichev, B. V. Zavodovsky, L. E. Sivordova, Yu. R. Akhverdyan, and Yu. V. Polyakova
Mediar Press
Rheumatoid arthritis (RA) is the second most common rheumatic disease. In recent decades, there has been an active search for and study of biologically active substances involved in the pathogenesis of RA, which can serve as a starting point in designing new drugs for targeted therapy of this disease. The hepatokine fetuin-A (FA) is one of these substances.Objective: to investigate serum FA levels in patients with RA.Subjects and methods. The investigation enrolled 110 patients with RA. All the patients underwent the following set of studies: general blood test and determination of the serum levels of C-reactive protein (CRP), serum FA, rheumatoid factor, anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage degradation products (CartiLaps), and urine creatinine. A control group consisted of 30 apparently healthy individuals whose serum FA level was determined in order to obtain reference values.Results and discussion. The normal FA level varied from 653.55 to 972.19 μg/ml. All the patients with RA were divided into two groups: 1) 23 patients with a low FA level (<653.55 μg/ml) and 2) 87 patients with a normal FA levels (≥653.55 μg/ml). The groups differed significantly in anti-CCP antibody concentrations, disease activity, radiological stages, functional classes, and the presence of complications. Patients with lower FA levels were noted to have increased CRP concentrations, erythrocyte sedimentation rate, and CartiLaps/urine creatinine ratio. The mean FA concentration was considerably and significantly lower in patients with higher DAS28 scores. Conclusion. Our investigation has revealed that there is a relationship between the levels of FA and the individual clinical manifestations of RA. The lower FA level is associated with higher disease activity and the aggressive phenotype of RA (the presence of anti-CCP antibodies, radiological stages III and IV, extra-articular manifestations and complications).

Fetuin A.Novel hepatokine in rheumatoid arthritis laboratory diagnostics
E. Papichev, B. Zavodovsky, Y. Polyakova, L. Seewordova and Y. Akhverdyan

Fetuin-A (α2-Heremans-Schmid glycoprotein, AHSG) is a glycoprotein mainly secreted by hepar in adults. It was shown, that AHSG is a positive as well as a negative acute-phase protein with pro- and anti-inflammatory effects. We studied serum levels of an AHSG in patients with rheumatoid arthritis (RA) and healthy controls in order to determine its role in the diagnostics of this disease. We measured serum levels of AHSG in 110 patients with RA and 30 healthy controls. To determine RA phenotype we measured rheumatoid factor and anticitrullinated protein antibodies. All patients were examined by the rheumatologist to identify clinical features of RA. Serum CRP and ESR were measured to assess inflammation. Mean level of AHSG in group with RA was 765,67±120,66 (Hereinafter M±σ), which was significantly lower than of healthy controls (812,76,2±76,2 μg/ml; p=0,0437). Insignificant difference of mean levels of AHSG was observed between men and women with RA (p=0,424). The reference ranges for AHSG measured from the healty controls were 653,55-972,19 ug/ml (M±2σ). We studied mean levels of AHSG according to the clinical and immunological manifestations of RA. AHSG levels were significantly lower within patients positive on ACCP, with moderate or high disease activity, with 2nd, 3rd and 4th x-ray stages and functional classes, with erosivity, extra-articular manifestations and complications. The moderate negative correlation was observed between AHSG level and CRP (r=-0,3146; p<0,001), ESR (r=-0,344; p<0,001) and DAS28 (r=-0,4334; p<0,001). In summary, AHSG mean levels were significantly different in patients with RA. It can be used to improve the diagnostics of RA activity, severity, extra-articular manifestations and complications.

Evgeniy Vasilievich Papichev

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