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Objective: to investigate in a multicenter study relationship between type 2 diabetes mellitus (DM) and clinical manifestations of osteoarthritis (OA). Material and methods. The study involved 767 patients aged 40–75 years with a confirmed diagnosis of stage I–III knee OA who had signed an informed consent form. The mean age of patients was 57.9±9.6 years, body mass index (BMI) was 30.8±6.4 kg/m2 and median duration of disease was 5 [2; 11] years. An individual record card was filled out for each patient, it contained anthropometric parameters, medical history and clinical examination data, knee pain assessment using a visual analogue scale (VAS), WOMAC, parameters of KOOS questionnaire and patient's global assessment of health. Results and discussion. DM was detected in 17.2% of cases. Patients were categorized into two groups according to the presence or absence of DM. In the presence of DM, more severe clinical manifestations of OA were noted. However, patients with DM were older, had higher BMI values, longer disease duration and were more frequently diagnosed with radiological stage III OA. After stratification by age and disease duration, individuals with DM retained worse pain scores according to VAS compared to patients without DM (median 51.5 [41.5; 70] mm versus 36 [25; 50] mm, p=0.049), total WOMAC index (1047.5 [792; 1260] mm versus 823 [536; 1145] mm; p=0.005) and its components (pain – 200 [160; 254] mm versus 155 [108; 230] mm, p=0.002; stiffness – 90 [50; 115] mm versus 60.5 [35; 100] mm, p=0.03; functional impairment – 765 [550; 918] mm versus 595 [350; 820] mm, p=0.009). Conclusion. Type 2 DM is common in patients with OA (in 17.2% of cases) and is associated with more severe clinical manifestations: greater pain intensity according to VAS and higher WOMAC scores (total index and its components).

NiSpAR is a non-interventional, multicenter study whose aim was to describe a cohort of patients with non-radiological axial spondyloarthritis (nr-axSpA) and approaches to its diagnosis in the Russian Federation.Material and methods. The study involved 20 research centers in different regions of the Russian Federation. The work consisted of two phases: retrospective data collection 12 months before enrolment in the study and prospective observation of patients in whom the diagnosis of nr-axSpA was confirmed (104 weeks).The study included 272 patients who met the inclusion and exclusion criteria (Full Analysis Set, FAS). The mean age of the FAS-population was 38.7±11.0 years. The diagnosis of nr-axSpA was confirmed in 159 (58.5 %) of the 272 patients. Of the remaining 113 (41.5%) participants, 57 (50.4%) did not have the information required to confirm the diagnosis, 34 (30.1%) did not have pelvic radiographs, and 22 (19.5%) did not fulfil the ASAS criteria for nr-axSpA.Results and discussion. The mean age of patients with nr-axSpA was 37.6±10.4 years, more than half of them (52.8%) were women. The median disease duration was 36 [12; 80] months. In half of the patients the disease duration was more than 2 years, in more than one third – less than 2 years. The median CRP and ESR values were 5.0 [2.0; 12.0] mg/l and 11.0 [5.0; 18.0] mm/h, respectively. The BASDAI averaged 3.5±2.0 and was >4 in more than half of the cases (64.2%). The mean ASDAS-CRP value reached 2.6±1.1. Only 1 in 5 participants (20.8%) had low axSpA activity, while in 61.1% it was high (44.7%) or very high (16.4%). An inactive state was found in a small number of patients (9.4%). Twenty two (13.8%) patients had treatment with biologic disease-modifying antirheumatic drugs (bDMARDs) in anamnesis, and 21 (13.2%) patients were still taking them.Conclusion. The results of the retrospective phase of the study show that in real-life clinical practice in the Russian Federation there is a continued positive trend towards improving the diagnosis of nr-axSpA. The median duration of the disease at the time of enrolment in the study was 3 years. The frequency of use of magnetic resonance imaging has increased by more than 1.8 times. At the same time, practitioners still have difficulties in establishing the diagnosis of nr-axSpA and a shortage of bDMARDs for treatment of these patients.

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.

Objective: to evaluate the efficacy and safety of simultaneous intramuscular administration of Traumeel® S and Zeel® T followed by therapy with the tablet medication Zeel® T in patients with knee osteoarthritis (OA) and concomitant cardiovascular diseases. Material and methods. The analysis included 119 patients aged 45–79 years (78.2 % women and 21.8 % men) with confirmed diagnosis of knee OA according to Altman criteria, stage II–III according to Kellgren–Lawrence and confirmed cardiovascular disease. The main indicator of efficacy was the change in pain intensity in the target knee joint according to the “Pain” subscale of the WOMAC questionnaire (A) at the final examination compared to the baseline. Other criteria were the dynamics of each symptom of knee OA according to the WOMAC questionnaire (pain, stiffness, and functional impairment, total score) on each visit, pain intensity in the target joint on a visual analogue scale (VAS), time it takes to travel 15 m, and the patient's overall disease assessment on the VAS. In addition, duration of use and dose of paracetamol (if used) were assessed, as well as quality of life by EuroQol and adverse events (AEs). Treatment safety was also analyzed in patients who had received at least one dose of the study drug. Results and discussion. WOMAC pain intensity decreased by on average of 3.8 points: from 7.6 to 3.8 points (95 % confidence interval, CI from -4.3 to -3.3). Data on changes in knee OA symptoms (pain, stiffness, and functional impairment) for each WOMAC subscale and the total score showed significant improvement at each follow-up visit (p < 0.0001). The VAS pain level decreased by 52%. An improvement in joint function was noted: the time it takes to travel 15 m fell from 19.5 to 16.4 s (p < 0.0001). The EuroQol quality of life score also improved from 57.1 ± 16.2 points at baseline to 71.1 ± 14.8 points on the 84th day of therapy. Thirty (25.2 %) patients had AEs, mainly neurological: headache (7.6 %) and hypoesthesia (1.7 %). No serious AEs were recorded. An association between AEs and study drug use was noted in 4 patients (headache, hypoesthesia, muscle cramps, and injection site pain). Conclusion. The results of the study confirm the efficacy and safety of the use of Traumeel® S and Zeel® T in patients with knee OA who have concomitant cardiovascular disease. During therapy, a significant decrease in pain and other clinical signs of OA (stiffness, limitation of physical activity) was observed, which allows us to recommend this treatment regimen for patients with comorbid pathology, as well as with the risk of developing of AEs during non-steroidal anti-inflammatory drugs therapy.

At the meeting of the Expert Council on May 20, the safety of treatment for patients with osteoarthritis (OA), the most common form of joint disease, was discussed. The first step in the treatment of OA should be the administration of symptomatic delayed-acting agents (SYSADOA) and nonsteroidal anti-inflammatory drugs (NSAIDs). However, given the current understanding of the pathogenesis of inflammation, as well as the fact that it is an active process involving multiple proinflammatory and pro-resolving mediators, it is reasonable to limit the cyclooxygenase-2 suppressive treatment and to include medications with multipurpose effects that contribute to the resolution of inflammation, in particular Zeel® T and Traumeel® S. Traumeel® S affects all stages of inflammation, mostly on the pro-resolving mediators synthesis, and Zeel® T affects chondrogenesis, inflammation, metabolic processes in cartilage tissue and prevents angiogenesis.It was found that it is advisable to use Traumeel® S when it is not possible to prescribe systemic NSAIDs for pain relief. The combination of the proven therapeutic efficacy of Zeel® T and Traumeel® S with a minimal number of adverse events and the absence of interactions with other drugs allows them to be used as an independent treatment regimen for OA.

Rheumatoid arthritis (RA) is the most frequent immunoinflammatory (autoimmune) rheumatic disease characterized by chronic erosive arthritis and systemic damage to internal organs. The data obtained in the course of basic research on deciphering the mechanisms of action of methotrexate (MT) and the materials of numerous randomized placebocontrolled trials, observational studies and national registries have strengthened the position of MT as the “gold standard” of RA pharmacotherapy and a key component of the “Treatment to Target” strategy. This was the basis for the development of new recommendations of the Association of Rheumatologists of Russia (ARR) concerning the use of MT in RA, according to which MT is considered as the drug of “choice” for induction and maintenance of remission in patients with early and advanced RA, including those who need combination therapy of MT with glucocorticoids, standard Disease-Modifying Antirheumatic Drugs (DMARDs), biologics and targeted synthetic DMARDs. Special attention is paid to the safety of MT therapy and the impact of MT on comorbid pathology associated with cardiovascular complications and interstitial lung disease. Implementation of the ARR recommendations into clinical practice will reduce the risk of disability and improve life prognosis in patients with RA.

In recent decades, there has been an increase in the prevalence and medical and social burden of osteoarthritis (OA) and nonspecific back pain in all countries of the world. The First Multidisciplinary Bilateral Russia-Uzbekistan Expert Council presented innovations in the prognosing, personalized prevention and adjuvant therapy of degenerative-dystrophic diseases of the joints and spine, the evidence base for the effectiveness and safety of the use of drugs that modify the course of OA (Disease-modifying osteoarthritis drugs, DMOADs): chondroitin sulfate, glucosamine sulfate, undenatured type II collagen for adjuvant pharmaconutraceutical support – prevention and adjuvant therapy (treatment) of OA and nonspecific lumbosacral pain. The expert counsil resolution presents an optimized algorithm for the management, prevention and adjuvant therapy of OA and non-specific back pain, maintaining the function of healthy joints after intense physical activity with the inclusion of the drug Chondroguard solution for intra-articular and intramuscular administration (INN – chondroitin sulfate) and a new pharmaconutraceutical from the DMOADs group – TRIO trademark Chondroguard® (Chondroguard®TRIO).

Osteoarthritis (OA) is the most common joint disease due to the increasing life expectancy of the world's population. Every 2nd patient over the age of 50 suffers from knee or hip OA, and this is directly related to the increased burden on healthcare. Accumulated data on the comorbid profile of patients with OA dictate the need to identify disease phenotypes in order to provide personalized care. Individual clinical manifestations of OA also require a differential approach: the pain treatment requires consideration of the patient's psycho-emotional profile and the possibility of involving nociceptive pathways in the process. However, due to the ambiguity of existing clinical guidelines, most experts note a number of difficulties in prescribing treatment for patients with OA.The resolution presents an agreed opinion of experts on the algorithms for managing patients with OA, starting from the primary level, with the gradual involvement of related specialists. Some issues of a personalized approach are considered depending on the presence of comorbid pathology and the severity of individual symptoms of the disease. The prospects of the combined use of pharmacological and non-drug methods of treatment are noted; emphasis was placed on the importance of rehabilitation measures at the first level of medical care, provided to patients with OA, long before the development of structural changes.The proposed algorithms for managing patients can be considered as the basis for future recommendations for managing patients with this pathology.

Objective: to evaluate the efficacy and safety of febuxostat (Azuriks®) in the treatment of patients with gout and concomitant diseases.Patients and methods. An observational, open-label, single-centre study of the results of febuxostat use in 85 gout patients with insufficient prior allopurinol efficacy or its intolerance. The median age of patients was 56.2 [49; 59] years, among them 83.5% were men. All patients had comorbid diseases, mainly cardiovascular pathology (76.5%) and chronic kidney disease (60%). The achievement of target values of uric acid (UA) during 4 months of urate-lowering therapy and its safety were assessed.Results and discussion. After 4 months of therapy with febuxostat, 25% of patients reached the target values of UA. Exacerbations at an early stage of the use of urate-lowering therapy were rare and were characterized by a lesser severity of the articular syndrome. Normalization of purine metabolism was accompanied by a decrease in the laboratory activity index (CRP level) to values corresponding to the interictal period of gout. Febuxostat was well tolerated.Conclusion. According to the data obtained, in patients with gout and concomitant diseases, febuxostat allows reaching target UA values in a short time without dose titration, while a high safety profile is noted.

The formation of chronic musculoskeletal pain (MSP) is a multifactorial process, in its pathogenesis mechanism of central sensitization (CS) plays an important role.Objective: to evaluate the effectiveness of etoricoxib at a dose of 60 mg per day in diseases accompanied by moderate/severe chronic MPS, with an additional analysis of the effect of this drug on the manifestations of CS.Patients and methods. An open observational study, 790 patients (71.6% women, mean age 54.5±13.0 years) with osteoarthritis and chronic nonspecific back pain received etoricoxib 60 mg/day for 2 weeks. The dynamics of pain, dysfunction, fatigue, sleep disturbances, general health assessment (GHA) on a numerical rating scale (NRS 0–10), as well as signs of CS according to part A of the CSI questionnaire were assessed.Results and discussion. After 2 weeks, the intensity of pain during movement, at rest and at night decreased on average by 58.8±24.1, 69.7±32.6 and 70.1±32.8% respectively; functional insufficiency by 58.2±22.5%, fatigue by 52.2±25.8%, GHA by 50.0±22.6%, sleep improvement by 54.3±25.8% was observed (p

The effectiveness of combined drugs, consisting of chondroitin and glucosamine (GA) in the treatment of osteoarthritis (OA) is discussed. Due to their high safety and pleiotropic effects, these drugs can be used in patients with OA (primarily with metabolic and inflammatory phenotypes) and comorbid diseases. The effect of oral chondroitin and GA on the intestinal microbiota is described: regulation of the composition, metabolic and immunological activity of intestinal microbiota. The relationship between the regular administration of chondroitin and GA and decrease in overall mortality and mortality from cardiovascular diseases, as well as the decrease of malignancy development risk is marked.

Background. Olokizumab is a new interleukin-6 (IL-6) inhibitor that has demonstrated good efficacy and safety for the treatment of adult patients with moderate to high-grade activity of rheumatoid arthritis in combination with methotrexate with insufficient efficacy of methotrexate monotherapy.Aim of the study was to evaluate the effectiveness of olokizumab in relation to the patient’s reported outcomes (PROs) based on the results obtained in the CREDO 1 phase III study.Material and methods. The study included 428 patients with rheumatoid arthritis who were randomized into 3 groups: group 1 – patients who received 64 mg of olokizumab subcutaneously every 2 weeks (q2w) (n=143); group 2 –patients who received 64 mg of olokizumab every 4 weeks (q4w) (n=142); group 3 – patients who had placebo q2w (n=143). PROs included: Health Assessment Questionnaire-Disability Index (HAQ-DI); Patient Global Assessment of Disease Activity (PtGA-VAS); Subject’s Assessment of Pain (VAS); fatigue according to the FACIT-F scale; quality of life according to the EQ-5D questionnaire; physical and mental components of the SF-36 scale. The effectiveness of olokizumab was evaluated by the dynamics of the average PROs values and the proportion of patients who reported improvement compared to the baseline level of ≥ minimum clinically important differences (MCID) for each PROs by weeks 12 and 24 of follow-up.Results. 396 patients out of 428 included completed the study. When included in the study, patients of different therapeutic groups did not differ in socio-demographic indicators, duration, activity of rheumatoid arthritis, as well as in PROs indicators. Olokizumab therapy, regardless of the dosage regimen of the drug, resulted in a significant improvement in all PROs compared to placebo after 12 weeks, and this improvement sustained until 24 weeks of therapy. The proportion of patients who reached and exceeded MCID at weeks 12 and 24 of follow-up was statistically significantly higher in both olokizumab groups compared to placebo for PtGA, VAS pain, HAQ-DI, FACIT-F. The number of patients who reached or exceeded the MCID on the physical component of the SF-36 scale at week 12 was significantly higher in both olokizumab groups, and at week 24 only in the group 2 compared to the placebo group. The mental component of SF-36 improved in a significantly higher percentage of patients in the group 2 compared to placebo group at weeks 12 and 24, while the group 1 did not significantly differ from placebo group in improving the mental component of SF-36.Conclusions. Olokizumab therapy in patients with moderate to high-grade activity of rheumatoid arthritis is associated with a significant improvement in all PROs. There was no significant difference between the dosage regimens of olokizumab.

Objective: to evaluate the efficacy and safety of glycosaminoglycan-peptide complex (GPC, Rumalon) used in patients with knee osteoarthritis (OA) and comorbidities (hypertension and/or type 2 diabetes mellitus (T2DM).Patients and methods: A 10-month multicenter (13 centers from 10 subjects of the Russian Federation) prospective study included 179 patients with Stages II–III primary tibiofemoral knee OA and comorbidity, a walking pain intensity of ≥40 mm on a visual analogue scale (VAS), and a need for nonsteroidal anti-inflammatory drugs (for at least 30 days in the previous 3 months). The efficiency of treatment was evaluated from the changes in VAS scores for knee pain intensity during walking, the overall WOMAC score and scores of its individual indicators, laboratory parameters, and ultrasound data. All the patients received 2 cycles of GPC treatment with 25 injections, by following the manufacturer's instructions.Results and discussion. Even at 2 months after starting the treatment, there was a statistically significant reduction in pain during walking from 60 (50–69) to 40 (27–53.5) mm on the VAS (p< 0.05), which persisted during the follow-up period. A similar pattern was found when assessing the WOMAC index and its components. The drug demonstrated an anti-inflammatory effect: a decrease in the number of patients with synovitis from 55.7 to 39.2% (p=0.02), the level of high-sensitivity C-reactive protein (hsCRP) from 3.2 (1.3–6.2) to 2.6 (1.2–5.7) mg/l (p< 0.05). GPC was ascertained to have a safety profile.Conclusion. The data of this study confirm the good therapeutic effect and safety of GPC Rumalon in knee OA patients with hypertension and/or T2DM. The drug is shown to have a rapid analgesic and anti-inflammatory effect, as well as a positive influence on all clinical manifestations of OA.

A combination of chondroitin and glucosamine is widely used in clinical practice as both a symptomatic and structure-modifying agent for the treatment of osteoarthritis (OA). The emergence of new drugs based on this combination substantially expands treatment options for OA therapy.Objective: to evaluate the efficacy and safety of Artroflex® that is a combination of chondroitin sulfate 400 mg and glucosamine sulfate 500 mg (CS + GS) to support joint health in patients with knee and/or hip OA.Patients and methods. When implementing an open observational research program, the results of using the CS + GS complex were assessed in 644 OA patients (74.7% women) (mean age, 58.0±14.6 years) who experienced moderate/severe pain and required to continuously take non-steroidal anti-inflammatory drugs (NSAIDs). The CS + GS complex was prescribed in a dose of 2 capsules per day for 3 months. The investigators estimated changes in pain on movement by a 0 to 10 verbal pain scale, general health (GH) by a 0–10 visual analogue scale), the Lequesne index, the need for NSAIDs, and patient satisfaction with treatment and its tolerance.Results and discussion. After 3-month therapy, there were decreases in pain intensity by 49.2±16.8%, GH scores by 45.6±18.1%, the Lequesne index from 9.0 [6.0; 13.0] to 5.0 [3.0; 9.0]; less than half (45.2%) of the patients still needed for NSAIDs. 82.2% of patients were satisfied or completely satisfied with treatment results; 89.6% reported good treatment tolerance.Adverse events (apparently associated with NSAID use) were recorded in 2.2% of cases. There were no serious complications that required CS + GS treatment discontinuation or hospitalization.Conclusion. The findings have indicated that Artroflex® used to support joint health is an effective agent that controls OA symptoms and has a good safety level.

The aim of the study was to develop ways to improve the diagnosis and treatment of systemic sclerosis (SSc)-ILD. Interstitial lung disease (ILD) is a common manifestation of SSc. In the territory of the Siberian Federal District (SFD), the number of patients with the progressive phenotype of SSc-ILD is approximately 750 people. When immunosuppressive therapy is ineffective and pulmonary fibrosis progresses, lung transplantation is indicated. The emergence of new possibilities of pathogenetic therapy currently requires studying the possibilities of their applications in real clinical practice on the territory of the SFD.Discussion. The results of a discussion of diagnostics, therapy, and routing of a rheumatology patient during the interdisciplinary observation of SSc-ILD in the SFD are presented. The reason for this discussion was the new data on the use of nintedanib in this category of patientsConclusion. To improve the efficiency of diagnosis and treatment of patients with SSc in the SFD, it is necessary to implement the principle of a multidisciplinary approach with the obligatory involvement of a pulmonologist and a radiologist (a specialist in CT diagnostics), and, if differential diagnosis is necessary in difficult clinical situations, of a pathomorphologist. An urgent task is the introduction of an algorithm for examining patients with SSc for the timely diagnosis of ILD in the territory of the Siberian Federal District. To improve the quality of medical care in the territory of the SFD for patients with ILD-SSc it is necessary to create a reference center in the city of Novosibirsk with the possibility of initiating anti-fibrosis therapy.

in 3 mL on patients with knee osteoarthritis (OA) in a multicenter prospective study. Materials and methods. 79 outpatients (predominantly females 81.0%) from 5 RF constituent territories with primary tibiofemoral KellgrenLawrence score grade II or III knee OA, 40 mm pain intensity during walking on visual analogue scale (VAS), requiring NSAIDs intake (for at least 30 days during 3 months prior to enrollment) were included into the study after signing the informed consent form. Mean age was 60.38.7 years, mean BMI 29.24.7 kg/m2, disease duration 6 (310) years. Grade II OA was documented in 68.4% of patients, Grade III in 31.6%. The study lasted for 6 months. Efficacy and safety evaluations were made based on VAS pain assessment, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) [WOMAC pain (0500), WOMAC function (01700), WOMAC stiffness (0200)], VAS patients health status, EQ-5D-based assessment of patients quality of life, global physicians and patients efficacy assessment, and daily NSAIDs requirements. Results. Obtained results demonstrate statistically significant VAS pain reduction during walking already in 1 week after intra-articular injection of the combination [respectively, 62 (5572) and 41 (3251) mm, р0.0001]. Moreover, pain continued to subside during all 3 months of follow up [in 1 month 28 (2042), in 3 month 22 (1437) mm]. A significant pan reduction achieved at Mo 3 persisted until Mo 6 20 (1442) mm, without documented pain increase. Similar trends were observed with total WOMAC score [1125 (8991540) at baseline, and 552 (309837) mm by the end of the study, p0.0001], and all WOMAC sub-scores [268 (189312) baseline WOMAC pain, 91 (48171) mm by the end of the study p0.0001; stiffness 101 (59130) and 40 (2061) mm, p0.0001; function 802 (6471095) and 402 (191638) mm, p0.0001, respectively]. Median time to the onset of therapeutic effect was 7 (518) days. Statistically significant improvement of patients quality of life by EQ-5D and general health status was observed during all follow up period [respectively, 0.52 (-0.020.59) and 0.69 (0.590.80), р0.0001; 48 (3060) and 72 (6080) mm, р0.0001]. One injection of the drug resulted in dose reduction or discontinuation of NSAIDs therapy: at baseline 76 patients (96.2%) were taking NSAIDs, in one week 31 (39.2%) patients discontinued NSAIDs, in 1 month 72.2%, in 3 months 73.4%, and by the end of the study at Mo 6 54.4% were not taking NSAIDs. These data were consistent with physicians and patients global assessment of the efficacy of treatment, who stated significant improvement and improvement in the majority of cases, with only few no effect or worsening cases documented in analyzed population. Adverse events, such as worsening of pain and/or swelling of the joint, were documented in 8 patients (10.1%); they resolved spontaneously or following NSAIDs intake. Conclusion. These results suggest that intra-articular injections of hyaluronic acid plus chondroitin sulfate in patients with knee OA are efficient and safe. A single injection of the drug resulted in statistically significant reduction of pain and stiffness, reduction in NSAIDs intake, as well as improvement in patients quality of life and function.

The conclusion of the Expert Council presents the results of discussing the diagnosis and therapy of interstitial lung diseases in systemic scleroderma. The reason for this discussion was the emergence of new data on the use of nintedanib in this category of patients.

The paper presents the results of a double-blind (BCD-085-3/AILAS) phase II clinical trial of the original interleukin 17A (IL17A) inhibitor BCD-085 prescribed at different doses to patients with active ankylosing spondylitis (AS) and those of an extended (BCD-085-3ext/AILAS-II) trial characterizing the efficacy and safety of this drug when used for a year.The objective of the AILAS study is to determine the therapeutically effective and safe dose of BCD-085 in the treatment of active AS. The efficacy, safety, and immunogenicity of BCD-085 during its annual use were additionally evaluated in the extended trial.Subjects and methods. The investigation enrolled 89 patients diagnosed as having active (BASDAI scores >4.0; mean spinal pain scores >4.0) AS that met the 1984 New York classification criteria. After the end of the screening period, the patients were randomized at a ratio of 1:1:1:1 in one of four groups that received 40; 80 or 120 mg of BCD-085 subcutaneously or placebo on day 1 of weeks 0, 1, 2 and then once every two weeks up to week 12. The primary end point was the number of patients who achieved an ASAS20 response at week 16. The investigation evaluated the safety of the drug, by calculating the total incidence of adverse events (AEs) and serious AEs (SAEs) and the number of cases of premature therapy termination because of AEs.Results and discussion. An ASAS20 response at week 16 was achieved in 72.7% of patients receiving 40 mg of BCD-085, in 81.8% of those receiving 80 mg, in 90.9% of those receiving 120 mg, and in 42.9% of cases in the placebo group (p=0.004). The superiority of BCD-085 over placebo was proven for 80- and 120-mg doses. The fastest and most pronounced effect was observed in patients treated with 120 mg of BCD-085. In the extended study, an ASAS20 response at week 52 was recorded in 86.4% of patients. One or more AEs during the first 16 weeks of therapy were reported in 11 (50.0%) patients of the 40-mg group; in 6 (27.3%) of the 80 mg group; in 4 (18.2%) of the 120 mg group and in 7 (31.8%) of the placebo group (p=0.183). The frequency and spectrum of AEs did not significantly differ in patients who received placebo and BCD-085 in different doses. No SAE was recorded.Conclusion. Phase II study yielded data demonstrating the high efficacy and good tolerance of BCD-085 in the treatment of active AS. The best effect and optimal tolerance were demonstrated for a dose of 120 mg.

The paper presents the results of the Osteoarthritis (OA) Expert Council held on September 8, 2019, which was attended by Russian and foreign specialists. The experts considered pharmacological treatment options for OA. The expert meeting resolution states that the treatment of patients with OA should be based on an individual assessment of the patient and on a modern evidence base of therapy efficacy.Treatment of patients with OA is based on the principles of evidence-based medicine that requires an integrated approach and the need of SYSADOAs prescription. Combined drugs with therapeutic dosages of chondroitin sulfate and glucosamine in the early stages of the disease are available as basic agents. The place of paracetamol in the anesthetic therapy algorithm in OA needs to be clarified. It is also noted that when choosing nonsteroidal anti-inflammatory drugs for OA treatment, it is important to take into account individual patient characteristics and the presence of comorbidities.

The current guidelines for prescribing analgesic therapy for osteoarthritis (OA) are based on the latest knowledge about the pathogenesis of this disease and the mechanism of action of analgesics. The leading principle of choosing analgesics is to assess the nature of pain and the patient's condition, adverse drug reactions. This is directly related to nonsteroidal anti-inflammatory drugs (NSAIDs) that are now the most important class of painkillers used in OA. Among the drugs of this class, meloxicam, a representative of the oxicam group, which relatively equally inhibits cyclooxygenase 1 and 2 and also affects the activity of microsomal prostaglandin E2 synthase 1, should be identified. This drug is characterized by a proven efficacy and a favorable safety profile. Nevertheless, the need for multifactorial evaluation of treatment-associated complications should be recognized as a priority when using any NSAIDs.

The paper gives data on the clinical efficiency and safety profile of long-term use of the infliximab (INF) biosimilar BCD-055 versus the reference drug Remicade® (REM) in a population of patients with active ankylosing spondylitis (AS).Subjects and methods. An international multicenter randomized double-blind Phase III clinical trial was conducted in 199 patients who were randomized into two groups in a 2:1 ratio and who received BCD-055 or REM at a dose of 5 mg/kg at 0, 2, and 6 weeks, then every 8 weeks. Efficiency assessment was made at 14, 30 and 54 weeks in patients who received at least one dose of INF [intent-to-treat (ITT)], as well as at 54 weeks in those who completed the study according to the Protocol (PP) (per protocol). The efficiency endpoints were the proportion of patients who had achieved ASAS20/ASAS40 responses; changes in BASDAI, BASMI, BASFI, MASES, and SF-36 scores. Immunogenicity was assessed by the proportion of patients in each group with identified binding and neutralizing antibodies (BAbs and NAbs) against INF. The safety analysis included the overall rate of adverse events (AEs), including those that met the respective criteria for serous AEs (SAEs), and grade 3–4 toxicity, as well as the number of cases of early termination of the study because of AEs and SAEs.Results and discussion. The ITT population included 199 patients and the PP one consisted of 161 people. The groups were not statistically different in the rate of and reasons for patient withdrawal from the study. A comparable number of patients achieved ASAS20/ASAS40 responses at 14, 30, 54 weeks (р ≥ 0.05). At 54 week, the proportion of patients who received BCD-055 and REM therapy and achieved an ASAS20 response was 67.42 and 52.24% in the ITT population (p = 0.053) and 80.91 and 68.63% in the PP population (p = 0.128). The BCD-055 and drug comparison groups achieved an ASAS40 response in 53.03 and 38.81% in the ITT population (p = 0.081) and in 63.64 and 50.98% in the PP one (p = 0.177). The proportion of persons with identified BAbs and NAbs was comparable: 21.26 and 3.15% in the BCD-055 group (p = 0.920) and 20.63 and 6.35% in the group REM (p = 0.443), respectively. It was found that the presence of NAbs did not affect the therapeutic response. Both groups did not differ in the detection rate and profile of AEs and SAEs or in the rate of patient withdrawal due to AEs. Most identified AEs were mild to moderate.Conclusion. The efficacy of the INF biosimilar BCD-055 used long in patients with AS did not significantly differ from that of the original drug REM; the safety profile of both drugs was comparable.

Objective: to investigate the effect of diacerein (Diaflex) on some components of metabolic syndrome (MS) in patients with knee osteoarthritis (OA).Subjects and methods. The multicenter open-label prospective study covered 55 patients aged 45 to 74 years with Kellgren–Lawrence Stage II–III knee OA and MS, with a pain intensity of >40 mm on a visual analogue scale, and with a disease duration of 1 to 30 years. The therapy duration was 6 months: Diaflex 50 mg/day for one month, then 50 mg twice daily for 5 months; the patients were followed up for the succeeding 3 months. During each visit, the efficiency and safety of treatment were evaluated; moreover, blood biochemical values were taken into account at the beginning and at the end of therapy.Results and discussion. There was a statistically significant improvement in WOMAC index (all its components and total value) and quality of life using EQ-5D in the first month of therapy and throughout the follow-up. Analysis based on the OMERACT-OARSI criteria indicated high treatment response rates in 92.5% of the patients at the end of therapy and in 92.2% three months after its completion. The body mass index and levels of low-density lipoproteins, triglycerides, glucose, and uric acid significantly decreased during treatment. Adverse events were detected in a small number (5.5%) of cases.Conclusion. Diaflex is an effective and safe drug in the treatment of knee OA in patients with MS. During therapy, there is a rapid and considerable reduction in pain and stiffness and an improvement in the functional state. In addition, the pleiotropic effects of the drug make it possible not only to effectively reduce weight, but also perhaps to improve the course of MS-associated conditions by the observed corrections of metabolic disturbances.

Glycosaminoglycan-peptide complex (GPC) (Rumalon®) is an injectable slow-release anti-inflammatory agent (SRIA) that has complex anti-inflammatory and metabolic effects. GPC has been successfully used in the treatment of osteoarthritis (OA) for several decades. The agent now returns again to Russian clinical practice. Objective: to evaluate the efficacy and tolerability of GPC in patients with knee OA, in whom other SRIAs have been previously ineffective.Subjects and methods. A study group consisted of 104 patients (92.3% women) (mean age, 63.2±8.5 years; body mass index (BMI), 28.5±5.4 kg/m2) with severe joint pain (≥40 mm on a 100-mm visual analogue scale (VAS)) and/or the need to regularly use nonsteroidal anti-inflammatory drugs (NSAIDs). All the patients received oral SRIAs in the last 6 months and had no improvement. At baseline, VAS pain intensity was 59.4±13.1 mm; the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain was 227.3±90.8; WOMAC stiffness, 97.9±42.1; WOMAC function, 769.2±326.1; total WOMAC scores, 1095.1±426.6. GPC was used by the standard scheme: 25 intramuscular injections every other day per treatment cycle; the results of treatment were assessed at 8 and 12 weeks by VAS and WOMAC pain scores, needs for NSAIDs, satisfaction with treatment (measured on a 1- to 5-pont scale where 1 = no improvement or deterioration and 5 = the best result).Results and discussion. At 8 and 12 weeks, VAS pain scores decreased by 30.1±18.3% and 36.9±16.9%, respectively; the reductions in WOMAC pain scores were 29.8±16.3 and 38.2±23.4%; WOMAC stiffness scores, 29.2±15.4 and 31.6±17.4%; WOMAC function scores, 27.7±14.7 and 30.6±18.4%; and total WOMAC scores, 27.2±13.5 and 33.6±18.0%. The changes in pain intensity and WOMAC scores were statistically significant in both followup periods (p

Objective/introduction. Evaluation of efficacy and safety of diacerein therapy in patients with knee joint osteoarthritis (OA) and metabolic syndrome (MS). Materials and methods. 55 outpatients (50 women and 5 men) with MS and stage 2-3 OA of knee joint according to Kellgren-Lawrence, with intensity of pain syndrome > 40 mm according to visual analogue scale (VAS) from 4 Russian Federation subjects were enrolled in the study. Average age of patients was 59.7 ± 7.3 years , mean BMI is 33 ± 5,49 kg/m2, the duration of the disease is 8 (5-10 years). Duration of the study was 9 months (6 months of therapy: 1 capsule (50 mg) per day for the first month, 2 capsules (100 mg) per day for the next 5 months, and follow-up for 3 months). Evaluation of the efficacy and safety of the treatment was conducted according to generally accepted criteria. All patients were underwent biochemical tests at the beginning and at the end of therapy. Results. The study resulted in a statistically significant reduction in pain when walking according to VAS as early as in 1 month from the beginning of treatment; the further significant improvement was observed during the entire 6-month therapy. Withdrawal of therapy (the observation period was 3 months) didn’t increase the pain syndrome. Evaluation according to Womac index also revealed identical regularity. A statistically significant improvement in the quality of life according to EQ-5D was also identified during the whole period of observation. By the end of the therapy, 92.5% of the patients were OMERACT - OARSI - responders and 64.2% of patients had completely withdrawn from NSAID. Against the background of the therapy, there was a significant decrease in BMI, LDL, TG, glucose, uric acid levels. Conclusion: The data obtained make it possible to recommend diacerein as a basic therapy for OA in patients with MS. On the background of therapy, the patients showed statistically significantly reduction in pain, stiffness, the need for NSAIDs, improved the quality of life and the function of the joints. In addition, the body weight decreases reliably, the lipidogram, carbohydrate and protein metabolism parameters also improved.

This article presents results from two clinical trials of infliximab biosimilar, BCD-055, including comparative data on the pharmacokinetics (PK), efficacy and safety of BCD-055 and innovator infliximab (IFX) in patients with ankylosing spondylitis (AS).Objective: The purpose of phase I clinical study ASART-1 was to evaluate the pharmacokinetic and safety profile of BCD-055 and to prove its equivalence with Remicade®, phase III study ASART-2 was conducted to evaluate the efficacy and tolerability of BCD-055 in comparison with Remicade® in patients with active AS.Patients and methods: Both studies were conducted as international multi-center randomized double-blind studies in direct comparison with innovator IFX. Inclusion and exclusion criteria, main examination methods, and drug regimens were the same in both trials. A total of 199 patients were enrolled in the studies. After the screening, the patients were stratified by CRP and BASDAI score, randomized (1:1 ratio in ASART-1; 2:1 ratio in ASART-2) into 2 arms and received BCD-055 or innovator IFX at a dose 5 mg/kg IV at 0, 2, 6 and then every 8 weeks (up to week 54). The primary endpoint for PK profile evaluation was the area under the concentration-time curve (AUC(0-tau)), maximum serum concentration of infliximab at steady state Cmax,ss. Efficacy was assessed by achieving ASAS20 at week 30, the endpoints for safety profile were the incidence of adverse events and serious adverse events during the maintenance-dosing phase and withdrawals from the study due to the safety reasons.Results: A total of 81 patients (ASART-1 study) were included in PK analysis, 199 patients were in efficacy and safety analysis. AUC(0-tau) value were 25,420,996.25±11,635,015.74 (ng/ml) Cmax,ss for BCD-055 and 26,114,705.71±12,102,376.9 (ng/ml)⋅h for INF innovator (p>0.05). Cmax,ss for BCD-055/Remicade® was 122,752 [99,401–151,553] ng/ml and 119,844 [98,120–132,772] ng/ml, respectively (p>0.05). ASAS20 was achieved at week 30 by 81.30% of the patients in the BCD-055 group, and 67.74% in the INF innovator group (p=0.061). The analysis of secondary endpoints (BASDAI, BASMI, BASFI, MASES, quality of life, chest excursion, and number of pathologically changed joints) showed no difference between the biosimilar and innovator groups. BCD-055 and innovator IFX showed highly similar safety profiles in both studies without cases of unexpected toxicity. The rates of AEs were equivalent for both drugs and were 48.48% and 58.21% of patients in the BCD-055 and Remicade®, respectively.Conclusion: BCD-055 is found to be equivalent in terms of PK, and showed the similarity in efficacy and safety profile compared with innovator IFX in patients with active AS.

The Russian biotechnological company «BIOCAD» has designed a chimeric monoclonal antibody against CD20 (BCD-020, Acellbia®) that is a biosimilar of rituximab (RTM; MabThera®, F. Hoffmann-La Roche Ltd., Switzerland). In recent years, there has been evidence that RTM can be used at lower doses than those given in the standard recommendations and instructions for the use of this drug. This serves as the basis for the BCD-020-4/ALTERRA (ALTErnative Rituximab regimen in Rheumatoid Arthritis) trial, the objective of which was to investigate the efficiency and safety of using Acellbia® (at a dose of 600 mg twice at a 2-week interval) as the first biological agent (BA) for methotrexate (MTX)-resistant active rheumatoid arthritis (RA). The investigation enrolled 159 patients aged 18 to 80 years with active RA. After 24 weeks 65.7 and 29.4% of patients achieved 20% improvement by the American College of Rheumatology (ACR) criteria in the Acellbia® + MTX and placebo (PL) + MTX groups, respectively (p

The European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) treatment algorithm for the management of knee osteoarthritis (OA), published in December 2014, provides practical guidance for the prioritization of interventions. This current paper represents an assessment and endorsement of the algorithm by Russian experts in OA for use in Russian clinical practice, with the aim of providing easy-to-follow advice on how to establish a treatment flow in patients with knee OA, in support of the clinicians’ individualized assessment of the patient. Medications recommended by the ESCEO algorithm are available in Russia. In step 1, background maintenance therapy with symptomatic slow-acting drugs for osteoarthritis (SYSADOA) is advised, for which high-quality evidence is provided only for the formulations of patented crystalline glucosamine sulphate (pCGS) (Rottapharm/Meda) and prescription chondroitin sulfate. Paracetamol may be added for rescue analgesia only, due to limited efficacy and increasing safety signals. Topical non-steroidal anti-inflammatory drugs (NSAIDs) may provide additional symptomatic treatment with the same degree of efficacy as oral NSAIDs but without the systemic safety concerns. To be effective, topical NSAIDs must have high bioavailability, and among NSAIDs molecules like etofenamate have high absorption and bioavailability alongside evidence for accumulation in synovial tissues. Oral NSAIDs maintain a central role in step 2 advanced management of persistent symptoms. However, oral NSAIDs are highly heterogeneous in terms of gastrointestinal and cardiovascular safety profile, and patient stratification with careful treatment selection is advocated to maximize the risk: benefit ratio. Intra-articular hyaluronic acid as a next step provides sustained clinical benefit with effects lasting up to 6 months after a short-course of weekly injections. As a last step before surgery, the slow titration of sustained-release tramadol, a weak opioid, affords sustained analgesia with improved tolerability.

The article considers the results of an international multicenter randomized clinical trial of the efficacy and safety of the brand-name drug rituximab (MabThera), a monoclonal antibody against CD20 antigen of B cells, and its biosimi-lar drug (Acellbia®) (the BIORA study) in patients with rheumatoid arthritis (RA) refractory to therapy with tumor necrosis factor-а inhibitors.Objective: to provide evidence for the therapeutic equivalence of Acellbia® and MabThera® and also to assess their interchangeability.Subjects and methods. The trial enrolled adult patients with active seropositive RA, who were randomized into two groups (1:1): 1) the patients who received Acellbia® 1000 mg intravenously on days 1 and 15; 2) those who had MabThera® in a similar way. When RA activity persisted at 24 weeks, there was re-randomization (1:1) with a partial overlap: Group 1 patients were randomized into group AA (the drug of the second therapy cycle was Acellbia®) or Group AM (that was MabThera®), the similar methodology was followed in Group 2 (Groups MM and MA). Throughout the study, the patients received methotrexate at a stable dose of 7.5—25 mg/week and folic acid at a dose of 5 mg/week. The follow-up lasted 48 weeks.Results and discussion. 24 weeks after treatment initiation, the ACR20 response was observed in 84.1% of the patients in the Acellbia® group (95% CI, 74.75—90.50) and in 87% in the MabThera® group (95% CI, 77.71—92.79%; p = 0.773), which suggests that the drugs are therapeutically equivalent. In the second phase of the study, the efficiency of therapy remained high; there were no differences in Groups AA/MM, AA/AM and MM/MA. In both phases, the safety profile of the drugs was comparable; the immunogenicity of treatment remained low. The findings suggest that the brand-name MabThera® and its biosimilar drug Acellbia® are equivalent. Switching from the biosimilar drug to the brand-name one and vice versa has no negative impact on treatment outcomes.

Abstract. The aim of the investigation was to study the immunological characteristics of RA patients with anaemia. Clinical and laboratory data including the percentage of the main lymphocyte subclasses, phagocyte and DTH-effector activity, serum concentration of immunoglobulins, the percentage of cells producing IFNγ and/or IL-4 and percent of monocytes producing TNF. We revealed some significant clinical, laboratory and immunological differences between RA patients and healthy donors and between patients with and without anaemia. Our data demonstrate RA anemic patients to have more severe disorders than patients without anaemia. We also revealed some significant immunological differences between RA patients and healthy donors and between patients with and without anaemia, including percent of cells producing IFNγ and/or IL-4. Our data permit to conclude that RA patients have many different immunological disturbances, more severe in anaemic patients.

The article contains results concerning combination frequency analysis for a wide number of three- to six-locus constellations of cytokine gene alleles, i.e., IL-1B T-31C, IL-6 G-174C, TNFA G-238A, TNFA G-308A, TNFA C-863A, IL-4 C-590T, IL-10 C-592A. The study was performed in a group of 104 patients with rheumatoid arthritis (RA) who were subject to basic therapy with methotrexate. An association was found between certain individual multi-locus allele combinations, and efficiency of the therapy, as defined by decrease in DAS28 index following 24 week of methotrexate treatment. An association was demonstrated between adverse effects of drugs used, and a "cytokine genotype" of the patients. Analysis of the results was carried out with respect to correlations between the levels of pro- and anti-inflammatory cytokine production and promoter polymorphisms of respective genes. We assume that further clinical research will allow to use our results as pharmacogenetic criteria in order to choose more effective personalized therapies, taking into account the genotypes of RA patients.

Non-steroidal anti-inflammatory drugs (NSAIDs) are most popular medications for the treatment of pain in common musculoskeletal diseases such as osteoarthritis (OA) and non-specific low back pain (LBP). However, the factors affecting the effectiveness of these drugs have not been determined fully. Aim: to identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. Materials and methods. An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). Results and discussion. Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p

Aim. To study the distribution of genotypes in the cytokine genes and their combinations with immunoregulatory activity in patients with type 2 diabetes mellitus (T2DM) and in healthy women. Subjects and methods. 586 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 212 women aged 28-69 years with T2DM complicated and uncomplicated by osteoporosis, were examined. Seven polymorphisms located in the promoter regions of the interleukin (IL) gene: TNF-α at positions С-863А, G-308A, G-238A, IL1B T-31C, IL6 G-174C, IL10 C-592A, VEGFA С-2578А were investigated. Restriction analysis of amplification products was applied. Results. There were high associations of the predisposition and resistance to the development of T2DM with a number of polylocus cytokine genotype combinations having pro- and anti-inflammatory, angiogenic, and immunoregulatory activities. The association of the cytokine genes with T2DM was found to be mediated in nature through a relationship of the genotypes to the high or low production of regulatory cytokines and to different factors of regulation of lipid and carbohydrate metabolisms, inflammation, and bone remodeling. Conclusion. The high odds ratio and high specificity of the detected genetic combinations allow one to hope that they will be clinically used as predictors.

Цель исследования. Комплексный анализ прогностической значимости выявления аллельных вариантов промоторных участков генов цитокинов в качестве генетических факторов риска развития остеопороза при сахарном диабете 2 типа. Материалы и методы. Было обследовано 625 человек. Контрольную группу составили 375 здоровых женщин без признаков остеопороза и сахарного диабета. С целью оценки роли генетических факторов при остеопорозе обследова- но 250 женщин находящихся в постменопаузальном периоде, разделенные на 3 группы: первая группа - 38 пациенток с первичным остеопорозом, вторая - 82 пациентки с остеопорозом на фоне сахарного диабета 2 типа, третья группа - 130 пациенток с сахарным диабетом 2 типа без признаков остеопороза. Группы были сравнимы по возрасту. Ис- следовались восемь полиморфизмов, локализованных в промоторных регионах генов интерлейкинов: TNFA в позициях С-863А, G-308A, G-238A, IL-1B T-31C, IL-4 C-590T, IL-6 G-174C, IL-10 C-592A, VEGFA С-2578А. Анализ исследуемых по- лиморфизмов проводился с использованием метода рестрикционного анализа продуктов амплификации. Результаты. Нами установлено, что наличие остеопороза является дискриминирующим фактором, разделяющим группу пациенток с сахарным диабетом по целому ряду генетических признаков. Группу этих признаков составили комбинации из 3-х, 4-х, 5-ти и 6-ти генотипов генов цитокинов: TNFA, IL-6, IL-1B, VEGF и IL-10. В группах больных сахарным диабетом 2 типа были проанализированы параметры, характеризующие инсулинорезистентность, эндо- телиальную дисфункцию и воспаление. У пациентов страдающих сахарным диабетом и остеопорозом отмечено до- стоверное повышение концентраций С-пептида, GLP-1 и снижение содержания GIP, лептина, PAI-1 и висфатина. В данной работе впервые описана ассоциированность уровней инсулина, резистина, лептина, глюкагона и PAI-1 с генотипами цитокинов при сахарном диабете 2 типа. Заключение. В результате исследования установлена связь развития системного остеопороза у здоровых женщин в постменопаузе и у пациенток с сахарным диабетом 2 типа с наличием определенными комбинациями аллельных вариантов генов цитокинов.