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Evaluation of the effect of new drugs should be carried out in randomized controlled trials (RCTs), and observational studies (OSs) are carried out to confirm and refine the results obtained in RCTs, for example, to study the effectiveness of drugs in large groups of patients who were not included in RCTs or had comorbidities or older age.Objective: to evaluate the effectiveness of Alflutop (AF) via OS of patients with osteoarthritis (OA) of the knee and/or hip joints and/or low back pain (LBP) with or without comorbid diseases.Material and methods. A multicenter prospective cohort OS was conducted in 163 clinical centers in 58 cities of the Russian Federation and included 22,525 patients with OA and LBP who received AF as a part of a planned treatment prescribed by a doctor, or self-prescribed and purchased in a pharmacy. Pain, satisfaction with therapy, health assessment, need for non-steroidal anti-inflammatory drugs (NSAIDs), and quality of life were recorded using the EQ-5D questionnaire.Results and discussion. After one treatment course with AF, improvement was detected in 98% of cases, there was a rapid positive trend with a significant decrease in pain, the median time to clinical effect was 8 [5; 10] days. Assessment of general health status and satisfaction with therapy improved significantly. In 94.5% of patients, the daily requirement for NSAIDs decreased.Conclusion. The first results from the OS confirm the symptomatic effect of AF.

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.

This review is focused on the issue of terminology in patients with multiple coexisting diseases in modern clinical practice. We articulate that multimorbidity is one of the leading problems in the field of public healthcare and that the treatment of these patients demands an integral approach derived from the combined nature of the pathology . It was shown that multiple coexisting diseases have a negative effect both on the course of osteoarthritis (OA) and its concomitant ailments, including higher risk of polypharmacy and death. Extra attention is paid to slow-acting symptomatic drugs, which often have positive pleiotropic effects towards both the OA and the concomitant diseases. In particular, there is more and more research showing evidence of the beneficial effects of chondroitin sulfate both on the OA treatment effectiveness as well as on the terms of cardiometabolic prognosis, mitigation of glucose metabolism deficiency and mortality.

About 10–40% of patients with osteoarthritis (OA) are not satisfied with the results of total arthroplasty (TA) of large joints. At the same time, the most common complication associated with the ineffectiveness of TA is postoperative pain (PP).Objective: to identify genes whose expression in the peripheral blood before TA is associated with an increased risk of PP developing. Patients and methods. Before TA, the blood of 50 patients with late-stage knee OA was examined; the control group consisted of 26 healthy individuals. The level of pain was assessed using the visual analog scale (VAS), the BPI short questionnaire, and the WOMAC index; the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of PP was determined 3 and 6 months after TA. The levels of matrix metalloproteinase protein (MMP) 9 and tissue inhibitor of metalloproteinase (TIMP) 1 were quantified by ELISA. Total RNA isolated from blood was used to determine the expression of caspase 3, MMP9, TIMP1, cathepsins K and S, tumor necrosis factor (TNF) α, interleukin (IL) 1β, and cyclooxygenase 2 genes using a quantitative real-time reverse transcriptase polymerase chain reaction.Results and discussion. PP according to VAS ≥30 mm was noted in 17 patients. Before TA, these patients had significantly increased expression of cathepsins K and S, caspase 3, TIMP1, IL1β, and TNFα genes compared to other patients with OA. ROC analysis revealed a statistically significant relationship between the expression of these genes and the likelihood of developing pain after TA.Conclusion. High expression of genes associated with degradation of the extracellular matrix (catepsins S and K, TIMP1), inflammation (IL1β, TNFα), and apoptosis (caspase 3) can serve as an important biomarker for the development of PP in patients with knee OA. To confirm the value of preoperative gene expression testing in predicting the onset of PP, further studies involving large cohorts of patients are needed.

The review systematizes modern data indicating effective pain control and a significant improvement in the functional activity of patients suffering from osteoarthritis (OA) using pharmaceutical substances of chondroitin sulfate (CS) and glucosamine (GA). The effect of a combination of CS and GA on subclinical inflammation (low-grade inflammation) in the joints, slowing down the progression of OA, reducing cardiovascular risk, metabolic disorders, etc. are discussed. There are promising reports of a possible decrease in overall mortality and mortality from cardiovascular diseases during long-term therapy with symptomatic delayed-acting drugs (SYSADOA). A wide range of pleiotropic effects of CS and HA allows us to classify these drugs as geroprotectors and recommend their use not only in OA, but also in various comorbid conditions.

Modern therapy of osteoarthritis (OA) consists of four sequential stages and includes non-pharmacological, pharmacological and surgical methods of treatment, and also assumes the possibility of collaborative management of the patient by doctors of different specialties, which allows to optimize the processes of diagnosis and treatment. The article presents simple and convenient algorithms, including diagnostic criteria, options for providing medical care, as well as situations (so-called red flags) that require referral of a patient to a specialist, primarily a rheumatologist. It has been demonstrated that the early use of the well-proven SYSADOA in any localization of OA, in particular the combined drugs of chondroitin sulfate and glucosamine, can increase the effectiveness of treatment, reduce possible functional disorders, and minimize the adverse effects of analgesic therapy.

Standard radiography in direct projection is the “gold standard” in the diagnosis of hand osteoarthritis (HOA). However, the currently clinically most severe “erosive” or “inflammatory” phenotype of HOA is characterized by the presence of inflammatory symptoms such as bone marrow lession (BML), synovitis and tenosinovitis, which are not visible on the radiograph by the nature of the study due to the low optical density. In addition, X-ray examination is planar and has no possibility of multiplanar visualization. This dictated the need to search for a more informative visualization technique in HOA.Aim – to compare the sensitivity and specificity of standard radiography and magnetic resonance imaging (MRI) techniques in determining the symptoms of osteoarthritis (OA) of the distal interphalangeal (DIP), proximal interphalangeal (PIP) and metacarpophalangeal (MCP) joints of the right hand; to determine the indications for the appointment of MRI in patients with HOA.Materials and methods. The study included 64 women with clinically verified diagnosis of HOA according to ask criteria. For the first time, X-rays of the joints of the right hand in the anterior-posterior projection and MRI were performed for each of them. Each patient completed the AUSCAN questionnaire. X-rays were described according to the Kellgren and Lawrence systems, magnetic resonance imaging was analyzed according to the modified OHOA system. The sensitivity and specificity of the methods were compared based on the detection of 4 symptoms detected by radiography and MRI: joint space narrowing (JSN), osteophytes (OP), erosions and subluxations. The average age of the patients was 65.28±6.82 years, the age of onset was 48.81±7.73 years, the duration of the disease was 15.0 (10.0–19.5) years.Results. Both methods showed approximately equal identification JSN symptom in DIP and PIP, 95% definition JSN in MCP. OP were detected in 88% of patients in DIP according to radiography and in 95% – using MRI (p>0.05). In PIP OP were observed in 70% of patients on radiographs and in 86% on magnetic resonance imaging, in MCP – in 45% and 66% of cases, respectively. Erosion in DIP were found in 41% of patients according to MRI and 34% as a result of X-ray examination, in PIP – in 27% and 13% of cases, in MCP – in 60% and 8% of cases, respectively. Subluxations were determined in DIP 23% on radiographs in 31% of cases by MRI, in PIP – in 8% and 6% (p>0.05), in MCP subluxations almost never met – in 3% of cases by conventional radiography.Conclusions. MRI in HOA can be used in the detection of erosive process, differential diagnosis with other diseases of the joints, determination of inflammatory changes in the hands and assessment of their severity, but has no significant advantages over standard radiography in determining the symptoms of degenerative-dystrophic nature (JSN and OP). Subluxations of the MCP joints are not typical for the HOA.

Currently chondroitin sulfate (CS) is the most studied drug from the group of «chondroprotectors». The article shows the role of CS in the treatment of osteoarthritis (OA): mechanism of action, clinical efficacy and safety in patients with OA with comorbidity. Evidence for the effectiveness and safety of the use of CS has been analyzed. The place of this drug in Russian and international clinical guidelines for the management of patients with OA is discussed.In domestic practice, the parenteral form of CS is often used in patients with OA. The parenteral form of CS for intramuscular and intra-articular administration (Chondroguard®) has a number of advantages, including the rapid onset of the effect. This enables reducing the dose in a short time or completely abandon the use of non-steroidal anti-inflammatory drugs (NSAIDs), which is extremely important for patients with OA with comorbidity. Chondroguard®can be recommended for initial use in exacerbations of chronic joint and back pain in OA, including in patients with relative and absolute contraindications for NSAID therapy.

Osteoarthritis (OA) is the most common pathology of the musculoskeletal system and is a serious medical and social problem. OA is of particular importance in elderly and senile people due to the high frequency of comorbid pathology. Pain relief is a priority in the formation of individual therapeutic programs for patients with OA, starting from their first request for medical assistance. At the same time, due to the ambiguity of existing clinical recommendations, most experts note a number of difficulties in prescribing treatment for patients with OA.The article presents a consensus position of experts regarding a complex approach to the choice of therapy in patients with OA at the initial visit to the doctor. The article discusses: current clinical guidelines for the management of patients with OA; most common problems in the management of patients with OA in real clinical practice; goals of treatment strategies for OA taking into account the risk factors for its progression; an algorithm of pain relief during initial treatment in patients with OA; prevention of OA exacerbations with the use of basic structure-modifying drugs; recommendations for the choice of non-steroidal anti-inflammatory drugs.According to experts, a rational approach to the treatment of OA is based on the combined use of non-drug and pharmacological methods with constant monitoring of therapy regimens and side effects. These recommendations can be considered disease-modifying strategies that in many cases allow improving functional status and achieving long-term remission in patients with OA.

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 systematic analysis of 37 post-genomic osteoarthritis (OA) studies (genomics, transcriptomics, proteomics, metabolomics) allowed to isolate 483 genes and corresponding proteins, their levels and activity disturbances are involved in the pathogenesis of the disease. These proteins can be conditionally subdivided into three groups: 1) structural proteins of connective tissue (CT); 2) proteins that support the activity of CT growth factors; 3) proteins that promote CT remodeling and degradation, as well as proteins associated with the regulation of inflammation (cellular response to tumor necrosis factor α, interleukin 1, bacterial lipopolysaccharides, NF-κB activation, etc.). It is important to note the epigenetic effects (DNA hypomethylation) associated with the pathogenesis of OA, which indicates the need for the use of vitamins group B in the therapy. Chondroprotectors (symptomatic slow-acting drugs) – chondroitin sulfate (CS) and glucosamine sulfate (GS), – in addition to reducing inflammation through inhibition of NF-κB and lipopolysaccharide receptors (Toll-receptors), also contribute to an increase in the expression of genes for structural CT proteins, CT growth factors and modulate the activity of CT remodeling and degradation proteins. These effects of CS/GS allowed to describe the complex mechanisms of the pathogenetic action of CS/GS in the treatment of OA.

Osteoarthritis (OA) is the most common joint disease. Searching for new treatment methods and regimens for OA is relevant.Objective: to evaluate the efficiency and safety of therapy with a symptomatic sustained-release drug (Alflutop) in combination with intra-articular hyaluronic acid (HA) injection versus monotherapy with HA in patients with knee OA in routine clinical practice.Patients and methods. A post-registration open-labeled prospective comparative randomized study was conducted to assess the results of treatment in 76 patients (31 men and 45 women; mean age, 49.3±8.5 years; body mass index, 28.4±0.8 kg/m2 ) in two clinical centers in Yekaterinburg and Perm. The patients were randomized into two equal groups, were homogeneous in terms of gender, the frequency of comorbidities, and vital signs (blood pressure, heart rate, and respiratory rate).Group 1 patients received Alflutop as 1-ml daily intramuscular injections (a total of 20 injections) + 2 ml of 1% intraarticular (IA) HA solution injections three times at 1-week intervals; Group 2 patients were given 2 ml of 1% intraarticular HA solution injections three times at 1-week intervals. As an additional therapy, the use of meloxicam 7.5–15 mg/day was permitted, and, if non-steroidal anti-inflammatory drugs were contraindicated, paracetamol 1–3 g/day might be used.Results and discussion. During treatment, both groups of patients showed improvement (compared to the baseline levels). At the same time, evaluating the intergroup values revealed clear differences: a more pronounced decrease in all WOMAC indicators in Group 1 patients: pain scores, 2 [1; 3] vs. 4 [2; 5] in Group 2 (pConclusion. The patients receiving the combination therapy with Alflutop + HA had the best treatment results in all the parameters assessed.

The paper provides a review of the data available in the literature on the relationship of pain to the risk of OA progression. Network analyses and numerous studies, including those conducted at the V.A. Nasonova Research Institute of Rheumatology, have confirmed that pain syndrome is one of the significant predictors of knee OA progression. The major class of medications for OA pain includes nonsteroidal anti-inflammatory drugs. The paper gives data on the efficacy of meloxicam in OA patients, which is widely used in both Russia and other countries of the world. Meloxicam is characterized by a good safety profile in the gastrointestinal tract, cardiovascular and renal systems. It is the drug of choice in patients with musculoskeletal diseases, in particular OA. Good results in severe pain syndrome have been shown by a step-by-step regimen of meloxicam when the injection formulation of the drug is used in the first days of treatment, and then, to consolidate what has been gained from therapy, its oral dosage form is administered in terms of concomitant diseases.

Osteoarthritis (OA) belongs to diseases with high comorbidity and most frequently concurrent with obesity, diabetes mellitus (DM), hypertension, and other cardiovascular diseases (coronary heart disease, atherosclerosis), gastrointestinal tract diseases, and chronic diseases of the lung and kidney. Irrational treatment of OA in the presence of comorbidity and without considering characteristics of drug interactions leads to a pronounced increase in the number of adverse reactions (ARs) and to aggravation of the course of all concomitant diseases. From this point of view, therapy seems to be relevant when the latter involves drugs that have both symptom- and structure-modifying properties and have a high safety profile.Objective: to compare the safety of alternating and standard treatment regimens with Alflutop® in patients with knee OA.Patients and methods. 130 patients were enrolled in the trial who had Kellgren-Lawrence Grade II–III primary tibiofemoral knee OA with pain intensity on walking ≥40 mm on a visual analogue scale and who needed to take nonsteroidal anti-inflammatory drugs (≥30 days in the previous 3 months). The patients were randomized into two groups: Group 1 was prescribed Alflutop® 1.0 ml intramuscularly (IM) daily for 20 days (a standard regimen); Group 2 was given 2 ml IM every other day (a total of 10 injections) (an alternating regimen). The duration of follow-up was 14 weeks. The safety of Alflutop® was evaluated by the incidence of ARs and serious ARs (SARs) varying in severity according to medical records, laboratory tests, physical examination, assessment of a patient' vital signs, and electrocardiography (ECG). The patients were examined at the beginning, at the end, and 1 month after therapy.Results and discussion. No SARs were recorded during the study period and follow-up. There were 10 ARs in the group of patients receiving Alflutop® in the standard regimen and 19 ARs in the other group (the alternating regimen). All ARs corresponded to mild and moderate severity, were unassociated with the test drug, and resolved by the end of the follow-up. 12-lead ECG identified only clinically insignificant abnormalities in the patients of both groups. Patients without DM displayed no clinically significant increase in glucose levels. Those with DM had no increased glycemia tendency. Biochemical studies in both groups revealed only clinically insignificant abnormalities, the frequency of which was insignificant.Conclusion. This study has confirmed the comparable high safety of Alflutop® in both standard and alternative therapy regimens. It has also shown that the drug has a good safety profile and can be recommended for wide clinical application in any use regimen: 1 ml daily (a total of 20 injections) or 2 ml every other day (a total of 10 injections).

Erosive osteoarthritis (EOA) of the hand is an osteoarthritis (OA) phenotype that is characterized by central and marginal erosions of the articular surfaces in the distal and proximal interphalangeal (DIP and PIP) joints and in some cases by a fairly aggressive course with obvious pain syndrome and a high level of functional impairment. Diagnostic criteria and management tactics for EOA patients are still under investigation.Objective: to evaluate the nature of the changes detected by hand joint magnetic resonance imaging (MRI) in patients with EOA and non-erosive OA (NEOA) of the hand.Subjects and methods. Examinations were made in 61 females meeting the American College of Rheumatology (ACR) diagnostic criteria for hand OA; the patients' mean age was 66.34+5.79 years; the median age at disease onset was 50 [45; 56] years; the duration of pain was 15 [11; 20] years. All the patients underwent MRI of the second-fifth DIP, PIP, and metacarpophalangeal (MCP) joints of the right hand. The patients also filled out the AUSCAN questionnaire. EOA and NEOA were detected in 30 and 31 patients, respectively.Results and discussion. The patients with EOA and those with NEOA were matched for gender, age, and disease duration. The DIP joints in patients with EOA were found to have significantly more frequently and a greater number of large osteophytes (OPs), (53 and 16%, respectively), joint space narrowing (JSN) (73 and 35%), degenerative collateral ligament changes (DCLCs) (93 and 55%), subluxations (47 and 13%), and bone marrow edema (BME) (57 and 19%) than in those with NEOA. Synovitides and subchondral cysts occurred with approximately the same frequency in EOA and NEOA. The PIP joints in patients with EOA significantly more frequently showed BME (37%) and DCLCs (97%) than in those with NEOA. Subluxations in the PIP joint of the right hand were encountered exclusively in patients with EOA. Their incidence was 17%. Degenerative symptoms (small, less often moderate sizes of OPs, JSN, and DCLCs) were identified with approximately the same frequency in both groups (p>0.05). The PIP joints in patients with EOA were significantly more often found to have BME (53 and 26%, respectively; (p0.05). Large OPs in the PIP joint were found relatively rarely. Subluxations in the PIP joints were undetected in both groups.Conclusion. The symptoms of active inflammation are predominant and degenerative changes are more pronounced in patients with EOA unlike those with NEOA. Articular surface defects in the PIP joints in patients with hand OA differ from erosions in those with rheumatoid arthritis. These CDs in EOA are much more common than those in NEOA; however, the nature of their occurrence is unclear; therefore, the patients in whom they have been found need dynamic monitoring.

Osteoarthritis (OA) is one of the most common diseases of the musculoskeletal system in the world. Some researchers call the small joints of the hands as being one of the most common sites of involvement in OA. Its most severe phenotype is considered to be inflammatory, or erosive, OA (EOA). Nevertheless, the radiographic pattern of this disease has not yet been sufficiently studied, and whether EOA is an independent form of OA, a regular later stage of the disease or an individual nosological entity, has not yet been resolved. Objective : to assess the location, frequency, and severity of radiographic symptoms and pain in patients with EOA and non-erosive OA (NEOA), to study the involvement of carpometacarpal (CMC), wrist, metacarpophalangeal (MCP) and radiocarpal (RC) joints in the pathological process in patients with EOA and NEOA of the hands. Subjects and methods . The investigation enrolled 64 women with hand OA who met the American College of Rheumatology (ACR) OA criteria. Hand joint images in the anteroposterior projection were first performed in all the patients. Each patient completed the AUSCAN questionnaire. The images were described according to the Kellgren and Lawrence classification. The mean age of the patients was 65.28+6.82 years; the age at onset of the disease was 48.81+7.73 years; its median OA duration was 15.0 [10.0; 19.5] years. According to the presence of erosions in the interphalangeal joints (IPJ) of the hand, the patients were divided into two groups: 1) EOA (n=23); 2) NEOA (n=37). Both groups were matched for age and disease duration (the mean age of patients with EOA was 68+6.15 years, the mean disease duration was 18.34+7.11 years; these in the NEOA group were 65.13+5.43 and 16.56+8.4 years, respectively). For age matching, 4 patients were excluded from Group 2. Results and discussion . Kellgren and Lawrence Stage II hand OA was detected most frequently (49%) and the most common radiographic symptoms of OA in the distal IPJ (DIPJ), proximal IPJ (PIPJ) and MCP joints were joint space narrowing (JSN) (100%, 100%, and 95%, respectively) and osteophytes (OPs) (88%, 70%, and 45% respectively). The least common conditions were subchondral osteosclerosis (SCOS) (5%), erosions (8%), and subluxations (3%) in the MCP joints, as well as subluxations in the PIPJ (6%). In the wrist, the most frequent sites of involvement was first CMCJ and scaphoid-trapezium-trapezoid joint (STTJ); their JSN was identified in 86 and 69% of patients, respectively; OPs were found respectively in 81 and 50% of cases. Changes in the RC joint (RCJ) were least common. EOA of the DIPJ and PIPJ was found in 15 (23%) patients with radiographic changes corresponding to Stages III—IV OA of the hand and in 8 (12%) patients with Stage II according to the Kellgren and Lawrence classification. The DIPJ in EOA versus NEOA showed significantly higher frequency of OPs (100 and 78%), SCOS (74 and 11%), cysts (61 and 24%), and subluxations (43 and 14%); the PIPJ — SCOS (43 and 5%), cysts (52 and 27%), and subluxations (17 and 0%; p

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.

Osteoarthritis (OA) belongs to diseases with high comorbidity and most frequently concurrent with obesity, diabetes mellitus (DM), hypertension, and other cardiovascular diseases (coronary heart disease, atherosclerosis), gastrointestinal tract diseases, and chronic diseases of the lung and kidney. Irrational treatment of OA in the presence of comorbidity and without considering characteristics of drug interactions leads to a pronounced increase in the number of adverse reactions (ARs) and to aggravation of the course of all concomitant diseases. From this point of view, therapy seems to be relevant when the latter involves drugs that have both symptom- and structure-modifying properties and have a high safety profile. Objective : to compare the safety of alternating and standard treatment regimens with Alflutop® in patients with knee OA. Patients and methods . 130 patients were enrolled in the trial who had Kellgren-Lawrence Grade II–III primary tibiofemoral knee OA with pain intensity on walking ≥40 mm on a visual analogue scale and who needed to take nonsteroidal anti-inflammatory drugs (≥30 days in the previous 3 months). The patients were randomized into two groups: Group 1 was prescribed Alflutop® 1.0 ml intramuscularly (IM) daily for 20 days (a standard regimen); Group 2 was given 2 ml IM every other day (a total of 10 injections) (an alternating regimen). The duration of follow-up was 14 weeks. The safety of Alflutop® was evaluated by the incidence of ARs and serious ARs (SARs) varying in severity according to medical records, laboratory tests, physical examination, assessment of a patient' vital signs, and electrocardiography (ECG). The patients were examined at the beginning, at the end, and 1 month after therapy. Results and discussion . No SARs were recorded during the study period and follow-up. There were 10 ARs in the group of patients receiving Alflutop® in the standard regimen and 19 ARs in the other group (the alternating regimen). All ARs corresponded to mild and moderate severity, were unassociated with the test drug, and resolved by the end of the follow-up. 12-lead ECG identified only clinically insignificant abnormalities in the patients of both groups. Patients without DM displayed no clinically significant increase in glucose levels. Those with DM had no increased glycemia tendency. Biochemical studies in both groups revealed only clinically insignificant abnormalities, the frequency of which was insignificant. Conclusion . This study has confirmed the comparable high safety of Alflutop® in both standard and alternative therapy regimens. It has also shown that the drug has a good safety profile and can be recommended for wide clinical application in any use regimen: 1 ml daily (a total of 20 injections) or 2 ml every other day (a total of 10 injections).

For the first time, the paper presents in detail the prevalence of osteoarthritis (OA) and considers the predictors of disease development and progression. The clinical classification of OA and its place in the ICD-10 are described. The clinical presentation of the disease is characterized in detail according to the localization of the process. It is noted that there is a change in the understanding of OA as a classic model of nociceptive pain. The paper depicts clinical, laboratory, and instrumental methods for diagnosing the disease, as well as classification and diagnostic criteria; much attention is paid to the current principles of OA therapy according to the Russian clinical recommendations and the guidelines of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the European League Against Rheumatism (EULAR).

Many patients with osteoarthritis (OA) tend to have comorbidities. This tendency is more frequently observed to increase with age. One of the comorbidities is type 2 diabetes mellitus (T2DM). Due to the higher prevalence of coexistence of these two conditions, it has been suggested that T2DM-associated hyperglycemia may adversely affect joint tissues and increase OA severity. However, the molecular mechanisms in the development of DM in patients with OA remain unclear. Objective : to trace the dynamics of T2DM development in patients with OA at the level of the expression of genes associated with glucose metabolism, joint destruction, and general regulation of metabolic processes. Patients and methods . Three patients with OA were followed up for 4—6 years, including the year of onset of T2DM. The clinical condition of the patients was analyzed once a year. Total RNA was annually isolated from their blood and used to determine the level of gene expression by real-time polymerase chain reaction. Results and discussion. The development of T2DM was shown to be accompanied by the increased expression of genes related to glycolysis, Krebs cycle, pentose phosphate pathway, matrix metalloproteinases and regulators of AMPKand mTOR metabolism. By contrast, the level of the hypoxia regulator HIF1a and hexosamine pathway genes was decreased. Conclusion . The occurrence of T2DM in the presence of OA is likely to be associated with the higher needs for cells for ATP energy and is accompanied by activation of the glucose assimilation pathways, as well as by the increased expression of the genes responsible for extracellular matrix destruction. This may be caused by impaired protein glycosylation due to inhibition of the hexosamine pathway.

Objective : to evaluate the efficacy and safety of Chondroguard® in the combined (intra-articular (IA) + intramuscular (IM)) and IM injection in patients with knee osteoarthritis (OA). Patients and methods . The study enrolled 150 patients with knee OA who were divided into two groups with 75 patients in each group. Group 1 received the drug (100 mg/ml) intramuscularly: 25 injections every other day, the first three injections at a dose of 100 mg, the fourth injection was started with a dose of 200 mg. Group 2 had five IA injections into the target joint at a daily dose of 200 mg with an interval of 3 days between injections, then 16 IM injections at 200 mg every other day. All the patients were prescribed nonsteroidal anti-inflammatory drugs (NSAIDs), such as meloxicam 15 mg. To determine the efficiency of treatment, the investigators estimated the following parameters: pain intensity on a visual analogue scale (VAS), the total WOMAC index and its components (pain, stiffness, and functional insufficiency), sensory and affective-emotional pain characteristics (for the target joint) according to McGill Pain Questionnaire (MPQ) scores. Clinical and biochemical blood tests, clinical urinalysis, coagulogram, and electrocardiography were performed in all the patients at the beginning and the end of the study. Results and discussion . Comparison of two Chondroguard® regimens showed that by the end of treatment, the pain intensity on VAS was significantly lower in Group 2 (IA + IM administration) than in Group 1 (16.81±13.49 and 21.88±13.24, respectively; p

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

Diacerein (D) belongs to a class of symptomatic slow-acting agents, has an original mechanism of action, and is widely used as a diseasemodifying antirheumatic drug to treat osteoarthritis (OA) in Russia and many countries of the world. The ability of the drug to affect the main symptoms and progression of OA has been shown in a number of well-organized clinical trials. Objective: to evaluate the efficacy and safety of D in patients with knee OA. Patients and methods . An open-label trial evaluating the efficacy and safety of D (diaflex) in patients with knee OA was conducted in accordance with the multicenter program «Osteoarthrosis: Assessment of Progression in Real Clinical Practice». The trial included 80 patients of both sexes with Stage II–III knee OA; mean age, 60.8±6.8 years (47–75 years); mean body mass index, 31.8±5.9 kg/m2; disease duration, 10.3±5.7 years (2–30 years). The duration of the trial was 9 months (6 months of therapy and 3 months of follow-up). Results . There was a statistically significant reduction in visual analog scale pain on walking just 1 month after therapy initiation (57.1±9.7 and 44.7±13.9 mm; p

Background:Administration of Chondroitin Sulfate for treatment of osteoarthritis included treatment types include systemic and parenteral therapies. The benefits of local therapies between difference route is ambivalent.Objectives:To evaluate effectiveness and safety of Chondroitin Sulfate (CS) by intramuscular and concomitant (intramuscular and intraarticular) route of administration in patients with knee osteoarthritis (OA).Methods:In total 150 patients with knee OA according by ACR criteria and with radiological stages 2 and 3 according to Kellgren-Lawrence were enrolled. Patients were divided by 2 groups: 75 patients (R) received course of 25 intramuscular injection every other day: at the first 3 injection’s in dose 100 mg, and in continue in dose 200 mg, 75 patients in 2nd group (N) received 5 intra-articular injections in target knee in dose 200 mg once per 3 days, in continue 16 intramuscular injections every other day in dose 200 mg. All patients received NSAID - meloxicam in stable dose 15 mg per day. All patients were checked by WOMAC, pain by visual analog scale (VAS), McGiIl Pain Questionnaire (MPQ). At the baseline, standard clinical examination for all patients were blood tests, urine test, coagulation panel and ECG.Results:After comparing of two groups by the end of course the intensity of pain by VAS was significantly greater in R group (21,88±13,24 vs 16,81±13,49; рConclusion:CS is effective decreased intensity of pain and stiffness, improved functional ability of joints both intramuscular and concomitant route of administration. However, significantly greater results at pain intensity by VAS shows combination: pain intensity by the end of course was significantly lower in group with concomitant intramuscular and intra-articular injections. Probably, it was associated with faster resolution of synovitis by intraarticular route of administration, that leads to choose this route for patients with comorbidity.Disclosure of Interests:None declared.

Background:There are many studies about investigation of risk factors (RF) of knee osteoarthritis (OA) radiologic progression. Especially, in patients with small disease duration. At the moment, there are ambivalent of results of previous studies, lead to uncertain role of synovitis.Objectives:The aim of study is to investigate relationship between knee OA synovitis and progression risk in patients with small disease duration during a follow-up period of 5 years.Methods:Eligible patients had knee OA based on ACR criteria with x-ray confirmation; baseline (BL) disease duration less than 5 years. Patients were evaluated at BL and at 5-year follow-up, using the questionnaires, clinical examination, knee joints pain by visual analog scale (VAS), musculoskeletal ultrasound and X-ray. Unadjusted p-values are presented.Results:Among 52 adults with knee OA (mean age ± standard deviation, 59.11 ± 8.95 years; 100% female) had the proportion of patients at BL 42.3% (n=22), 46.2 % (n=24), 11.5% (n=6) by disease stage 1,2 and 3, respectively. Patients were categorized into 2 groups by progression during 5 years from BL based on changes of radiological stage. After 5-years follow-up period the progression of knee OA was established in 14 patients (1 group) and in 38 patients (2 group) the progression by radiological stage was absent. BL patients’ characteristics were similar across 1st and 2nd groups: mean age 58.29±7.68 vs 56.05±8.74, р>0.05; disease duration 3.43±1.34 vs 3.47±1.33, р>0.05. Individuals with knee OA progression had worse knee joints pain during walking (60.36±18.33 vs 48.71±17.81, р=0.043), higher body mass index (BMI) (34.45±4.60 vs 28.92±4.92 kg/m2, р=0.001), higher frequency of knee synovitis by clinical examination (42.9% vs 10.5%, RR=4.07; 95%Cl (1,3-12,3), р=0.01) and by musculoskeletal ultrasound (57.1% vs 18.4%, RR=3.1; 95%CI (1.38-6.96), р=0.009). At 5-years follow-up knee pain was significantly greater for 1st group (69.64±18,49 vs 55.76±12.76, р = 0.003), higher BMI (35.74±5.83 vs 30.64±4.64, р = 0.002), also higher frequency of knee synovitis by clinical examination (57.1% vs 10.5%, RR = 5.4 (95%Cl 1.9-15.2), р=0.001) and by musculoskeletal ultrasound (50% vs 13.2%, RR=3.8 (95%Cl 1.4-10.0), р=0.009). Spearman correlation coefficients between radiologic stage and OA progression factors were indicated: between radiologic stage and knee pain during walking (r = 0.34, pConclusion:The proportion of patients with knee synovitis by clinical examination and musculoskeletal ultrasound data increased by 5-year follow-up from BL. Synovitis is a significant predictor of radiographic progression of knee OA in patients with small disease duration.Disclosure of Interests:None declared.Figure 1.

Background:Objectives:To identify factors associated with pain in patients with early knee osteoarthritis fulfilling ESKOA criteria [1].Methods:50 patients (46 women (92%); 4 men (8%)) fulfilling ESKOA criteria were enrolled in the trial, every participant signed up the consent form. Median age of patients was 47 ± 8 yrs (36 – 63 yrs), body mass index (BMI) was 28.5 ± 4.9 kg/m2 (40% of patients had obesity). Every patient, after signing the standard informed consent form, was addressed to a physician, who would fill in an individual case report form (CRF), including anthropometric parameters, history of OA, comorbidities and physical examination data. Knee pain was also assessed with the use of visual analog scale (VAS). All participants underwent knee X-ray according to the standardized fixed flexion protocol with the use of positioning frame [2].Results:Most of the patients (70%) were between the ages of 35 and 50 and only 15 of them (30%) were older than 50 years. Median knee pain duration was found to be 16 (12-20) weeks, intensity of VAS – knee pain was 46 mm (42-50). Median number of episodes of knee pain (in the last 6 months) was 3 (2-6); 30 participants (60%) had episodes of knee pain lasting less than a week, 8 of them (6%) had pain lasting for around a week, 12 of them (24%) had episodes of pain lasting more than one week. In most patients (74%) pain relieved with time, without any additional therapy. Most of the patients had episodes of knee pain linked to increased overload (48 (96%)), when squatting (41 (82%)), most of the patients also reported pain when climbing up and down the stairs (80%) and short joint stiffness when starting movement (76%). Knee pain after sitting was reported in 54% of cases and 20 participants (40%) also reported some walking limitations due to knee discomfort.Knee X-ray revealed that most of the patients had I Kellgren&Lawrence (K&L) stage knee OA (picture 1). All the included participants had ESR (7 (5-10 mm/hr)) and CRP (1.24 (0.8-2.2 mg/l)) within normal range.Picture 1 – Radiological knee OA stage (K&L) distribution in the study groupIn the Spearman correlation analysis, we have estimated the factors, which may be associated with more severe pain in patients with early knee OA fulfilling the ESKOA criteria. We found out that higher BMI (r=0.38, р=0.02), presence of metabolic syndrome (r=0.37, р=0.008) and hypertension (r=0.29, р=0.04), as well as walking limitations (r=0.33, р=0.008) are associated with knee pain.Conclusion:The use of ESKOA criteria in patients with short duration of knee pain can facilitate diagnosis of osteoarthritis on an early stage. In addition, the acquired data show that timely diagnosis and correction of certain components of metabolic syndrome may be beneficial for the course of knee pain intensity in patients with early knee OA, further continuation of this trial is necessary.References:[1]Migliore A et al. Rheumatol Int. 2017 Aug;37(8):1227-1236.[2]Mazzuca SA et al. Osteoarthritis Cartilage. 2008 Dec;16(12):1555-9.Disclosure of Interests:None declared.

Background:Objectives:To evaluate the relationship of hyperuricemia (GU) with the course of knee osteoarthritis (OA) and the components of metabolic syndrome (MS).Methods:The prospective study included 107 women aged 40-75 y.o, with a reliable diagnosis of I-III Kellgren J. - Lawrence J. stage of knee OA (ACR), who signed an informed consent. The average age of patients was 59.1 ± 8.9 y.o. (from 38 to 74), the duration of the disease was 9 (4-12) years. The average values of the body mass index (BMI) corresponded to obesity (30.6 ± 5.7 kg / m2), waist circumference (WC) - 93.9 ± 12.1 cm. An individual card was filled out for each patient, including anthropometric parameters, anamnesis and clinical examination data, an assessment of knee joint pain according to VAS, and concomitant diseases. All patients underwent standard X-ray of the knee joints, DEXA scan of the lumbar spine and total hip, and laboratory examination.Results:Hyperuricemia was diagnosed in 26.2% of patients. Patients with GU had a higher BMI and WC (pTable 1.Comparative characteristics of OA patients with and without GUParameterOA Patients with GU (n = 28)OA Patients without GU (n = 79)pAge, y.o.61 (53-68)60 (54-66)0.33Duration OA, years10 (6-14)7.5 (3-12)0.06WC, сm99.3 ± 12.892.2 ± 11.40.02BMI, kg/m233.5 ± 5.630 ± 5.60.04The size of the medial space of joint according to X-ray, mm2.3 (1.2-3.3)3.2 (2.0-4.3)0.02The size of the osteophytes of the femur, mm5.8 (3.7-6.3)2.9 (1.7-4.5)0.02BMI L1-L4, g/сm21.18 (1.12-1.24)1.0 (0.86-1.15)0.04BMI total hip, g/сm21.05 (1.0-1.13)0.9 (0.82-0.98)0.04CRP, mg/l2.8 (1.9-6.2)1.9 (1.2-3.6)0.007COMP, ng/ml31.9 (27.6-45)24.2 (18.9-38.7)0.05Leptin, ng/ml46.2 (36.5-72)30.5 (19.5-45.6)0.03TG, mmol/l1.97 (1.61-2.41)1.26 (0.87-1.63)0.002Creatinine, mmol/l79 (74.9-86)68 (62-74)0.0001ALT, mmol/l26.5 (17.2-32.9)17.9 (13.2-21.7)0.003АST, mmol/l22.5 (18.5-27.8)18.9 (16.8-21.9)0.02Conclusion:GU may be an aggravating predictor of not only MS-associated diseases such as obesity, dyslipidemia, but also OA. Thus, at high levels of uric acid, more advanced radiological stages of OA, high values of the BMD of the axial skeleton and increased values of CRP, COMP are noted. In this connection, therapeutic interventions of OA in patients with GU should also be aimed at reducing the concentration of uric acid, which may provide a slowdown in the progression of the disease. Further study of this issue is needed.Disclosure of Interests:None declared

Background:In 20-44% of patients with osteoarthritis of the knee joints neuroplastic changes occur due to central sensitization (1,2), which is the rationale for complex therapy, including centrally acting drugs, for more effective pain control.Objectives:To evaluate the efficacy and safety of combination therapy with NSAID and anticonvulsant in comparison with NSAID monotherapy in patients with osteoarthritis of the knee joints and signs of central sensitization or nocyplastic painMethods:The study included 60 women with osteoarthritis of the knee joints (OAK) with signs of nocyplastic pain. Nocyplastic pain were revealed by neuropathic scales (DN4 questionnaire > 4 points), subject to the absence of patients lesions of the somatosensory nervous system. All patients were randomized into two age- and sex-matched groups: group I (n=30) received combination therapy with aceclofenac and pregabalin, group II (n=30) - monotherapy with aceclofenac. The observation period was 42 days and included three visits. All patients underwent a clinical and neurological examination, we assessed the overall WOMAC index, pain intensity at rest with the visual analogue scale (VAS), nocyplastic pain (DN4 and Pain DETECT questionnaires), anxiety and depression (HADS questionnaire) and the quality of life (EQ-5D questionnaire).Results:The intensity of pain at rest according to VAS in patients of group I significantly decreased after 14 days (visit 2) and even further after 42 days (visit 3) (64.0 [50.0; 72.0] vs 49.0 [33.0; 55.0] vs 33.5 [22.0; 49.0] p = 0.006). In group II the intensity of pain at rest also decreased after 14 days (visit 2) (63.0 [41.0; 72.0] vs 48.0 [35.0; 58.0] p The dynamics of neuropathic pain indicators according to the DN4 and Pain DETECT questionnaires was as follows: group I (visit 1-3) DN4 (6.0 [5.0; 7.0] vs 3.0[1.0; 4.0], p=0.001) and Pain DETECT (17.0 [16.0;20.0] vs 8.0 [5.0; 14.0], p=0.001). Group II DN4 (6.0[5.0;6.0] vs 5,0 [3,0; 6,0],p=0,05), Pain DETECT (17,0 [15,0; 19,0] vs 16.0 [14,0; 19,0],p=0,53).The overall WOMAC index decreased significantly in both groups.Significant positive dynamics in terms of the level of anxiety (9.0 [7.0;14.0] vs 7.0 [4.0;10.0], p=0.001), depression (8.0 [5.0;10.0] vs 6.5 [4.0;9.0], p= 0.03) and quality of life (0.52 [-0.02;0.52] vs 0.52 [0.52;0.59], p=0.01) was observed compared to baseline in group I but not in group II. Before the start of therapy, the groups were comparable in the studied parameters, however, after 42 days, anxiety (7.0 [4.0;10.0]vs 9.0 [7.0;12.0], p=0.02) and depression levels (6.5 [4.0;9.0] vs 8.0 [6.0;9.0], p=0.05) were statistically different. Moreover, the median anxiety and depression levels still exceeded 7 points in group II, indicating the presence of anxiety and depression.Conclusion:Combination therapy of chronic pain with signs of nocyplastic pain with pregabalin and aceclofenac in patients with knee osteoarthritis has been shown to be effective in terms of pain intensity, the presence of neuropathic descriptors and the severity of anxiety compared with aceclofenac alone.References:[1]Hochman JR, French MR, Bermingham SL, Hawker GA. The nerve of osteoarthritis pain. Arthritis Care Res (Hoboken). 2010;62:1019–23.[2]Hochman JR, Gagliese L, Davis AM, Hawker GA. Neuropathic pain symptoms in a community knee OA cohort. Osteoarthr Cartil. 2011;19:647–54.Disclosure of Interests:None declared.

Background:Objectives:To evaluate the relationship between arterial hypertension (AH) and the course of knee osteoarthritis (OA).Methods:The prospective study included 109 women aged 38-75 y.o., of I-III Kellgren J. - Lawrence J. stage of knee OA (ACR), who signed an informed consent. The average age was 59.3 ± 8.7 y.o. (from 38 to 74), the average duration of the OA was 7 (4-12) years. The average values of the body mass index (BMI) corresponded to obesity (30.9 ± 5.4 kg / m2), waist circumference (WC) – 94.4 ± 11.7 cm. An individual card was filled in for each patient, including anthropometric parameters, anamnesis and clinical examination data, assessment of knee joint pain according to VAS, WOMAC, KOOS and DN4 indices, and concomitant diseases. All patients underwent standard X-ray of the knee joints, laboratory examination.Results:AH was diagnosed in 69.7 % patients with OA. Patients were divided into 2 groups, according to the presence or absence of AH (Table 1). Patients with AH were older, had a higher BMI, WC, a longer duration of menopause and significantly earlier its onset (pTable 1.Comparative characteristics of OA patients with and without AHParametersPatients with AH(n=76)Patients without AH(n=33)pAge, y.o.61 (57-68)55.5 (49-58)WC, cm92 (90-105)86.5 (84-90)Age of menopause, y.o.50 (47-52)55.5 (49-58)0.02Duration of menopause, years14 (7.5-19)7 (4-8)Duration of OA, years10 (5-15)4 (1-6)0.001VAS pain score, mm49 (40-57)42 (24-50)0.02WOMAC pain, mm189.5 (140-250)140 (108-162)0.001WOMAC stiffness, mm77.5 (42-100)56 (33.5-71.5)0.01WOMAC functional impairment (FI), mm651 (547-902)546.5 (320-663.5)0.002Total WOMAC, mm899 (728-1280)734 (526.5-882)0.001KOOS, points0.47 (0.36-0.57)0.6 (0.53-0.75)DN4, points2 (1-3)1 (0-2)0.01Overall health status, mm45 (35-55)36.5 (28.5-48.5)0.02The size of the medial space of joint according to X-ray, mm2.45 (1.35-4.35)3.6 (2.8-4.3)0.07CRP, mg/l2.38 (1.47-4.85)1.21 (0.69-2.53)Leptin, ng/ml37.4 (26.5-53.3)23.6 (15.1-40.2)0.01IL-6, pg/ml0.7 (0.4-1.2)0.45 (0.3-0.7)0.03ESR, mm/h14 (7-18)7 (6-12)0.02We founded positive (р Conclusion:Thus, we found that AH in patients with knee OA is affected by a variety of variables, both related to traditional CVD factors and to OA itself, and the correlations found are approximately equal in strength. The results obtained require further study, and it is possible that preventive measures aimed at reducing the traditional risk factors of diseases of the circulatory system, or correcting existing CVD, will contribute to a more favorable course of OA.Disclosure of Interests:None declared

Background:The most severe phenotype of osteoarthritis (OA) is currently considered to be an inflammatory or erosive phenotype (EOA). There is currently no reliable x-ray picture of this disease in the literature, and the question of whether it is an independent form of OA, a natural more pronounced stage of progression, or a separate nosology is debated in the literature.Objectives:To identify the localization, frequency, and severity of pain and radiological symptoms in patients with EOA and non-erosive (NOA) disease in the interphalangeal (DIP and PIP) and metacarpal (MCP) joints of the hands.Methods:64 women with diagnosis of OA of the hand (HOA) joints according to the ACR criteria were included into study after signing the informed consent form. Mean age was 65.28 ± 6.82 years (48-77), mean BMI 27,7 ± 4,4 kg/m2, mean disease duration 12 ± 8,1 years. Individual patient’s medical record included relevant anthropometric data, records from case history and clinical examination, AUSCAN scores, patient’s articular status. Instrumental diagnostic methods included plain radiography of the hand joints in an anterior-posterior projection. The images were described in accordance with the Kellgren&Lawrence (K&L) system.When evaluating radiographs of 64 patients with HOA, the most common was stage II (49%) according to K&L, and the most common symptoms in distal (DIP), proximal (PIP) interphalangeal and MCP were joint space narrowing (JSN) (100%, 100%, and 95%, respectively) and osteophytes (OP) (88%, 70%, and 45%, respectively). Subchondral osteosclerosis (SO) (5%), erosions (8%), and subluxations (3%) in MCP, as well as subluxation in PIP (6%) were less common. Statistica 10.0 was used for statistical analysis.23 patients had EOA, 37 had NOA. Depending on the presence of erosions in interphalangeal joints patients were divided into 2 groups comparable in terms of age, age of OA onset and duration of disease (the average age of patients with EOA interphalangeal joints was 68 + 6.15 years, and mean disease duration 18,34 + 7.11 years; in the group without erosive changes in the average age amounted to 65,13±5.43 years, mean disease duration of 16.56±8.4 years).Results:EOA DIP and PIP was detected in 15 (23%) with radiological changes corresponding to stages III-IV of HOA and in 8 people (12%) with stage II on the K&L scale. Patients with stage I according to standard radiography had no erosive process.In DMFs OP (100% and 78%, OR=1.28, 95%, CI [1.08-1.5], p=0.02), SO (74% and 11%, OR=6.8, 95%, CI [2.6-17.8], pConclusion:DIPs is most often affected in OA of interphalangeal joints, less often PIPs, the most common symptoms are JSN and OP. At EOA in addition to more frequent detection OP, cysts, SO, subluxations in DIPs, SO, cysts and subluxations in PIPs, there is also significantly more pronounced pain according to AUSCAN data, it can be concluded that EOA is more severe in comparison with the non-erosive form of HOA.Disclosure of Interests:Danil Kudinsky: None declared, Ludmila Alekseeva Grant/research support from: Bayer, Alexander Smirnov: None declared, Alexander Volkov: None declared, Olga Alekseeva: None declared, Elena Taskina: None declared, Anastasiia Sukhinina: None declared

Background:Osteoarthritis (OA) is a chronic rheumatic disease, which involves pain, limited inflammation, and local destruction of the knee joint. OA pain is a major clinical symptom, which limits working capacity and denotes an important indication for joint replacement in the end-stage OA. In spite of significant number of positive outcomes, chronic postoperative pain represents a major adverse consequence of surgery, which is observed in 10-40% of OA patients. Therefore, identification of patients potentially capable of developing chronic postoperative pain prior to surgery could significantly improve therapy outcome. Recently we hypothesized that genes related to pain sensitization whose expression is upregulated in about 10-40% of the examined end-stage OA patient cohort might be responsible for postoperative pain. Retrospective analysis of gene expression in the peripheral blood of end-stage OA patients before joint replacement surgery revealed that expression of cathepsins S and K, caspase 3, and MMP-9 genes might be associated with postoperative pain development [Ann Rheum Dis,78, suppl 2:A520].Objectives:To examine the validity of our hypothesis in the prospective study.Methods:We examined peripheral blood of 26 healthy volunteers (average age 55±8.3 years old) and 40 end-stage OA patients (average age 56.5±8.9 years old) undergoing joint replacement surgery. Patients were examined before and 6 months after surgery. Pain was assessed prior to surgery using VAS index and neuropathic pain questionnaires DN4 and PainDETECT. Functional activity was evaluated by WOMAC. After surgery pain indices according to VAS of 30% and higher were considered. MMP-9 and caspase 3 protein levels were quantified by ELISA. Total RNA isolated from whole blood was used in expression studies for caspase 3; metalloproteinase (MMP)-9; cathepsins K and S genes. These were performed with quantitative real-time RT-PCR.Results:Out of 40 patients pain complaints were obtained from 9 patients (22,5%) after 6 months’ post-surgery. Prior to surgery all the examined genes were significantly upregulated in the patients who developed post-operative pain compared to healthy controls and those subjects who did not develop pain after surgery. However, no difference in the levels of the examined pain-related and functional indices in patients, who developed pain or not, was noted before surgery. ROC curve analyses confirmed significant associations (pConclusion:High cathepsin S gene expression in the peripheral blood of the end-stage OA patients measured prior to joint replacement surgery could serve an important biomarker of post-operative pain development.Disclosure of Interests: :None declared

Objective To investigate the potential of the baseline gene expression in the whole blood of disease-modifying anti-rheumatic drug-naive rheumatoid arthritis (RA) patients for predicting the response to methotrexate (MTX) treatment. Methods Twenty-six control subjects and 40 RA patients were examined. Clinical, immunological and radiographic parameters were assessed before and after 24 months of follow-up. The gene expressions in the whole blood were measured using real-time reverse transcription polymerase chain reaction. The protein concentrations in peripheral blood mononuclear cells were quantified using enzyme-linked immunosorbent assay. Receiver operating characteristic curve analyses were used to suggest thresholds that were associated with the prediction of the response. Results Decreases in the disease activity at the end of the study were accompanied by significant increases in joint space narrowing score (JSN). Positive correlations between the expressions of the Unc-51-like kinase 1 (ULK1) and matrix metalloproteinase 9 (MMP-9) genes with the level of C-reactive protein and MMP-9 expression with Disease Activity Score of 28 joints (DAS28) and swollen joint count were noted at baseline. The baseline tumor necrosis factor (TNF)α gene expression was positively correlated with JSN at the end of the follow-up, whereas p21, caspase 3, and runt-related transcription factor (RUNX)2 were correlated with the ΔDAS28 values. Conclusions Our results suggest that the expressions of MMP-9 and ULK1 might be associated with disease activity. Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to MTX therapy.

Osteoporosis (OP) in rheumatoid arthritis (RA) is 2–3 times more common than in the population; however, the data on the risk factors (RFs) of OP in this disease are ambiguous.Objective: to study RFs for OP in RA within the framework of the multicenter program “Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment”.Subjects and methods. The trial enrolled 261 women (mean age 56.7±11.4 years) with RA; of them 151 (59%) patients were found to have OP (Group 1) and 107 (41%) were not (Group 2). All the patients underwent unified clinical, laboratory, and instrumental examination.Results. Comparison of the patients with and without OP showed that the women with OP were older (59.5±10.8 and 52.9±11.2 years, respectively; p < 0.01) had longer RA duration (14.5±9.2 and 11±8.0 years; p < 0.01), higher Health Assessment Questionnaire (HAQ) functional disability index scores (1.7±0.8 and 1.4±0.9; p < 0.01), higher C-reactive protein (CRP) levels (13.5 [7; 31] and 11 [2,7; 26] mg/l; p < 0.01); a larger number of erosions (49 [11; 90] and 8 [1;36]; p < 0.01), and a more marked joint space narrowing (112 [90; 131] and 77 [51; 102]; p < 0.01). The women with OP received longer (72 [26.5; 120] and 48 [11; 79.5] months; p < 0.01) and more frequently glucocorticoids (GC) orally (65.6 and 38.3%; p < 0.01) and as pulse therapy (41.2 and 20.4%; p < 0.01), had a larger cumulative dose (14.4 [5.4; 24.2] and 7.2 [1.5; 14.4] g; p < 0.01) and a larger GC dose at their examination (6.0 [4.0; 8,0] and 5.0 [4.0; 6.0]mg/day, respectively; p = 0.05).Conclusion. The presence of OP in RA correlates with age, RA duration, articular dysfunction, CRP levels, X-ray change magnitude, hormone therapy duration, and a cumulative GC dose.

Objective. To evaluate the symptom- and structure-modifying effect of Alflutop compared to placebo (PL) in patients with knee osteoarthritis (OA). Material and methods. The study included 90 patients with knee OA (according to the criteria of the Russian Association of Rheumatologists) at the stage 2–3 (according to the Kellgren-Lawrence scale); pain score when walk- ing ≥ 40 mm (assessed using the visual analog scale). All the patients provided an informed consent. The patients were randomly divided into two groups: group 1 (n=45) received an intramuscular injection of 1 mL Alflutop for 20 days with 6-month intervals for 2 years (a total of 4 courses for 2 years); group 2 (n=45) received an injection of PL (iso- tonic sodium chloride solution) in the same way. Ibuprofen at a dose of 600–1200 mg/day was administered as con comitant therapy. To evaluate the structure-modifying effect of Alflutop, X-ray of the knee joint was performed at the beginning and end of the study; the level of biochemical markers (CTX-II and COMP) was determined at the beginning, after 3 months, and at the end of the study. A statistical analysis was performed using the Statistica 10 software package. Results. After the 2-year follow-up, a statistically significant negative trend was detected less frequently in the group of patients treated with Alflutop compared to the PL group (6.1 and 38.4%, respectively). The statistically significant delay in joint space narrowing was observed in patients who received Alflutop in contrast to patients who received PL (the numerical score of the joint space, the Wilcoxon test; p=0.0003). An increase in osteo- phyte size was observed in 72% of the patients receiving PL, and only in 27% of the patients receiving Alflutop (medial and lateral osteophytes of the femoral bone, the Wilcoxon test; p=0.0078; medial and lateral osteophytes of the shin bone, the Wilcoxon test; p=0.0001 and p=0.0039, respective- ly). Augmentation of subchondral osteosclerosis was determined more often in the PL group (the McNemar's test; p=0.0313). The level of the marker of cartilage degradation CTX-II tended to decrease after 3 months of Alflutop therapy, which has persisted until the end of the study. This indicates a decrease in the articular cartilage degradation. In the PL group, the CTX-II level remained unchanged. A tendency to an increase in the level of the marker of cartilage degradation COMP was found in the PL group. Conclusion. Based on double-blind, placebo-controlled, randomized study, the structure-modifying effect of Alflutop in knee OA has been proved. Alflutop delays the radiographic progression of knee OA, joint space narrowing and osteophyte growth, and reduces the degradation of the articular cartilage matrix.

In patients with rheumatoid arthritis (RA), bone fractures occur 1.5-2 times more frequently than in the population. They often lead to reduced quality of life, to disability and death in the patients. It should be noted that risk factors (RFs) for fractures have not been studied on a sufficient sample in Russia; there are no recommendations on the prevention of fractures in this category of patients. Objective: to compare groups of RA patients with and without a history of fractures to further identify possible RFs for fractures. Subjects and methods. The trial included 254 patients aged 18 to 85 years, diagnosed with RA, from the database of the multicenter program «Osteoporosis in rheumatoid arthritis: Diagnosis, risk factors, fractures, treatment», who had been followed up in 2010 to 2011. The patients were divided into two groups: 1) 101 (39.8%) patients with a history of low-trauma fractures and 2) 153 (60.2%) patients without a history of fractures. In Group 1, the patients were older than in Group 2 (mean age 59.8 and 56.1 years, respectively). Menopause was recorded in 88.1 and 77.8% of cases, respectively. The groups differed in the duration of RA an average of 15.5 and 11.5 years, respectively Results. The fractures in the history were associated with the use of glucocorticoids (GC), their higher cumulative dose and use duration. In Group 1 patients, the bone mineral density (BMD) was lower in all study skeleton portions and more frequently corresponded to osteoporosis. RA complications, such as amyloidosis and osteonecrosis, were more common in the patients with a history of fractures. Conclusion. In RA patients, the most likely RFs of fractures are age, the long-term intake of large-dose GC, low BMD, the severe course of RA, and the presence of its complications.

The gene expression of mTOR, autophagy-related ULK1, caspase 3, CDK-inhibitor p21, and TNFα was measured in the peripheral blood of osteoarthritic (OA) patients at different stages of the disease aiming to establish a gene expression profile that might indicate the activity of the disease and joint destruction. Whole blood of 65 OA outpatients, 27 end-stage OA patients, 27 healthy volunteers, and knee articular cartilages of 28 end-stage OA patients and 26 healthy subjects were examined. OA outpatients were subjected to clinical testing, ultrasonography, and radiographic and WOMAC scoring. Protein levels of p70-S6K, p21, and caspase 3 were quantified by ELISA. Gene expression was measured using real-time RT-PCR. Upregulation of mTOR gene expression was observed in PBMCs of 42 OA outpatients (“High mTOR expression subset”) and in PBMCs and articular cartilages of all end-stage OA patients. A positive correlation between mTOR gene expression in PBMCs and cartilage was observed in the end-stage OA patients. 23 OA outpatients in the “Low mTOR expression subset” exhibited significantly lower mTOR gene expression in PBMCs compared to healthy controls. These “Low mTOR” subset subjects experienced significantly more pain upon walking, and standing and increased total joint stiffness versus “High mTOR” subset, while the latter more often exhibited synovitis. The protein concentrations of p70-S6K, p21, and caspase 3 in PBMCs were significantly lower in the “Low” subset versus “High” subset and end-stage subjects. Increases in the expression of mTOR in PBMCs of OA patients are related to disease activity, being associated with synovitis more than with pain.

Background Osteoporosis (OP) is 2–3 times more frequent in rheumatoid arthritis (RA) patients as compared to general population with associated 1,5–2,5 – fold increased risk of fractures. Femoral neck fracture is the most unfavorable prognosis and outcome in these patients, compromising their quality of life. Objectives To identify major risk factors of femoral neck OP in female RA patients. Methods The study included 206 female RA patients (ACR criteria), aged 20–75 years (mean age 56,6±11,2 years). An individual patient9s file contained social and demographic data, anthropometric parameters, case history, clinical examination and lab findings, traditional OP risk factors, patient9s joint status and comorbidities. Hand and distal feet X-ray was taken in each case. Van der Heijde modified Sharp method was used to score the erosions and joint space narrowing in hands and feet. Axial bone mineral density (BMD) was measured using DEXA scan. DEXA T-score was used in post-menopausal women, and Z-score – in menstruating women. Results Femoral neck OP was diagnosed in 68 patients (33%), while in 138 (67%) no OP was found. Patients with and without OP were of comparable age (58,7 ± 12,3 vs 55,5 ± 10,2 years, p =0,06), but differed in disease duration (12 (7; 22) vs 11 (7; 15) years, p =0,04) and total Sharp score (181,5 (92; 267) vs 112 (59; 173), p =0,006). OP patients were taking higher average daily dose of glucocorticosteroids (GC) during the previous year (5 (2,5; 7,5) vs 2,5 (1,3; 5) mg/day, p =0,03) and were prescribed greater number of intra-articular (i/a) GC injections vs patients without OP (8 (3; 18) vs 6 (2; 10), p =0,04, respectively). Analysis of traditional OP risk factors identified lower body weight in OP patients (62,8 ± 11,4 vs 69,6 ± 12,4 kg, p p =0,007). Higher incidence of femoral neck fractures within the immediate family members was found in OP patients family history (16,4 vs 2,9%, RR =5,57, 95% CI 1,82–17,07, p =0,001). Multifactorial analysis identified the following major femoral neck OP risk factors: total Sharp score, average daily GC dose during the previous year, total number of intra-articular GC injections, and menopause; the contribution of these variables in OP development was assessed (discriminant function coefficients: 0,006; 0,37; 0,07; 2,91, respectively) to suggest a model (with the area under the ROC curve equal to 0,926), allowing prediction of femoral neck OP with high accuracy, equal to 89,7%. Conclusions The degree of erosive joint destruction in hand and feet (based on total Sharp score), average daily GC dose during the previous year, total number of intra-articular GC injections, and menopause are major risk factors of femoral neck OP in female patients with RA. Disclosure of Interest None declared

Dynamic electroneurostimulation (DENS) is a type of percutaneous electroneurostimulation with a differentiation approach to choosing exposure areas and to optimizing electrocutaneous therapeutic action on the reflexogenic areas and acupuncture points for analgesia and for the treatment of functional disorders. Objective: to study the clinical efficiency and safety of therapy using a DiaDENS-PC apparatus in the treatment of knee osteoarthritis (OA). Subjects and methods. A multicenter randomized double-blind placebo-controlled study was conducted in 132 knee OA patients with pain value above 40 mm on visual analogue scale (VAS) and Lequesne’s index of 4–12. In a study group (n = 66), DENS was carried outwith a DiaDENS-PC apparatus using a trailing electrode applicator to the knee target in a Therapy stimulation mode at a frequency 77 Hz, a power of 15 units. In the placebo group, the similar procedure was performed with a switched-on placebo apparatus that did not differ in appearance from the working apparatus; but produced no electrical pulses. The treatment cycle consisted of 10 sessions lasting 30 min. Changes in Lequesne’s algofunctional index were primary end point. The results of the Get-Up to Go test (in seconds) and changes pain on VAS and WOMAC were used as secondary end points. Results and discussion . Both groups showed a statistically significant reduction of painand improvement of Get-Up and to Go test results by the end of the treatment course (p < 0.0001). Therewas a statistically significant difference in pain in the compared groups after a treatment session during the first (p = 0.037) and second (p = 0.010) visits. The analgesic effect of therapy was observed to persist in the DENS group 2 weeks (p = 0.006) and 1 month (p = 0.070) after treatment termination. After 10 sessions, there was a statistically significant difference between the groups in the Get-Up and Go test (p = 0.033) and Lequesne’s index (p = 0.022). Both groups exhibited a significant decrease in the total WOMAC scores. In the DENS group, positive changes in all subscales were statistically significant starting from the second visit whereas in the control group, the total WOMAC scores improved only at the expense of the pain subscale.

Background Rate of vertebral body fractures and spinal deformities is 2-fold higher in RA patients compared to general population, compromising their quality of life. Objectives To identify major risk factors of lumbar osteoporosis (OP) in RA female patients. Methods The study included 220 RA female patients (ACR criteria), aged 20-75 y. (mean age – 57,1±10,8 y). An individual patient9s file contained anthropometric parameters, social and demographic data, case history, clinical examination and lab findings, traditional OP risk factors, patient9s joint status, info on concurrent diseases, pain intensity evaluation by VAS and evaluation of general health status. Bone mineral density (BMD) was measured using DEXA scan. DEXA T-score was used in post-menopausal women, and Z-score - in menstruating women. Results Patients were grouped in two arms: patients with lumbar spine OP – 74 (33,6%) and without OP in the lumbar spine – 146 (66,4%). OP patients were somewhat older (59,8±10,2 vs 56±11,1 y., p =0,02 respectively), greater extent of functional impairment (HAQ >2) (43,4 vs 29,5%, RR =1,47, 95% CI 0,98–2,21, p =0,05), longer use of glucocorticosteroids (GC) (72 (36–110) vs 50 (12–95) mo, p =0,05), and at higher average daily doses during the previous year (6,3 (2,5–8,75) vs 5 (2,5–7,5) mg/day., p =0,01), as well as higher total GC dose 14,4 (5,4–25,8) vs 9 (2,4–16,5) g, p =0,02). RA activity by DAS28 and current radiographic lesions (Van der Heijde modification of Sharp method) was comparable in both groups. Analysis of traditional OP risk factors identified lower body weight in OP patients (64,4±10,6 vs 69,2±12,9 kg, p =0,01) and post-menopause status in the majority of them (94,6 vs 74%, RR =1,28, 95% CI 1,14–1,42, p =0,0001). Discriminate analysis identified the following major lumbar spine OP risk factors: RA duration, severe functional impairment by HAQ, average GC daily dose in the previous year and menopause. Based on identified factors and their coefficients a model was suggested (with area under the curve – AUC- equal to 0,784), allowing to predict lumbar spine OP with high precision, equal to 74.5%. Conclusions Lumbar spine OP in RA female patients is to great extent predetermined by RA duration, higher degree of functional impairment by HAQ, average daily GS dose in the previous year and the menopause status. Disclosure of Interest None declared

Objectives Through the Programme of the Russian Association of Rheumatology for the diagnosis, prevention and treatment osteoporosis (OP) in patients with RA we evaluated the ten year probability of major osteoporotic fracture by FRAX for Russia in patients with RA, and identified prevalence osteoporosis treatment in patients with high or low risk of osteoporotic fractures (OF). Methods Trough the Programme of a large amount of patients with RA from 12 clinical centers in Russia 560 patients aged 41 to 89 years were selected and have been evaluated the risk of OF by FRAX. Results 485 (87%) women and 75 (13%) men were involved in our study. Female average age was 60,46 years, male one was 60,1 years. OP was diagnosed in 97 (17%) patients, 74 (13%) had a history of OF, however, of these people OP treatment was approved only 86 (87%) and 36 (49%), respectively. 185 (33%) patients have indications to approve OP treatment, defined using FRAX, only 57 (31%) of these people treatment was imposed. Assignment of treatment didn't need for 375 (67%) patients, however treatment was approved 48 (13%) from them. 77 (73%) patients were taking prescribed medications, 49 (60%) of them – bisphosphonates plus calcium and/or vitamin D supplementation, 14 (18%) – calcium and vitamin D, 11 (14%) – calcitonin, 3 (4%) - strontium ranelate. Osteoporosis evaluation (DXA) was performed in 421 (75%) patients, including 54 (72%) patients with history of OF and 128 (69%) patients with indications to approve OP treatment, defined using FRAX. Conclusions Osteoporosis management is not quite enough in patients with RA in Russia. There is substantial variation in the quality of risk evaluation of the osteoporotic fractures, osteoporosis evaluation and treatment. Introduction of FRAX for allocation of group of patients with RA with a high risk of fracture will contribute to a personalized approach to approving treatment. Disclosure of Interest None declared

The present review is devoted to the risk factors of osteoporosis progression in patients with rheumatoid arthritis (RA), both relevant and irrelevant to the main disease. It is assumed that the most important predictors of the bone mineral density decrease is severe course of RA, significant functional disability (according to HAQ), glucocorticoid therapy, elderly age, low body mass index and menopause. However, despite the vast amount of studies, results on the risk factors of osteoporosis remain ambiguous and require further investigation.

Objective: to evaluate the symptom- and structure-modifying effect of alflutop versus placebo (PL) in patients with knee osteoarthrosis (OA).Subjects and methods. The trial enrolled 90 patients with knee OA (ACR criteria and Kellgren–Lawrence Stages II–III) and pain on walking ≥ 40 mm on a visual analogue scale (VAS) who signed their informed consent. The patients were randomly assigned to two groups: 1) 45 patients who received alflutop as 1-ml intramuscular injections for a 20-day cycle at a 6-month interval for 2 years (a total of 4 cycles during 2 years); 2) 45 patients who were given PL (isotonic sodium chloride) injections following the same pattern. As concomitant therapy ibuprofen was used in a dose of 600–1200 mg/day. The efficiency of treatment was evaluated using the OMERACT-OARSI criteria, changes in the three scales WOMAC, EQ-5D, pain and general health status (GHS) on VAS; 15-m walking time, and therapeutic efficiency assessment by the physician and patient. At the beginning and at the end of the investigation, knee joint X-ray and magnetic resonance imaging were performed and the time course of changes in the level of biochemical markers (CTX-II and COMP) was determined to evaluate the structure-modifying effect of alflutop. Adverse reactions were recorded at each visit. A Statistica 10.0 data package was used for statistical analysis.Results. At the end of the trial, the use of aflutop versus PL showed a significant pain reduction in an intent-to-treat population (p=0.003). Analysis of a per protocol population indicated that the pain reduction was more marked in the aflutop group. WOMAC showed that the differences between the groups in the absolute value of pain intensity reduction were significant. A significance stiffness reduction was seen in the alflutop group at Visit 3; no significant decrease was found in the PL group (p < 0.001). Improvements in joint function and reduction in joint WOMAC index were noted in the alflutop group after the first cycle of therapy and these remained throughout the follow-up (p = 0.001). At Visit 6, significantly better quality of life was observed only in the alflutop group (p = 0.0045). Analysis of the GHS scale revealed that the differences between the groups were significant (p = 0.03). In the alflutop and PL groups, the therapy respondents were 73 and 40%, (p = 0.001). Among the alflutop-treated patients, 79% reduced the daily dose of nonsteroidal anti-inflammatory drugs (NSAIDs) and 21% completely discontinued using them. In the PL group, only 23% needed daily lower intake of NSAIDs.Conclusion. The double-blind randomized placebo-controlled trial established the symptom-modifying effect of alflutop in patients with knee OA.

Objectives To assess the efficacy and safety of Rceclofenac (200mg/day) versus Diclofenac (100mg/day) therapy during three month in patients with knee osteoarthritis (OA). Methods 200 outpatients (each group consists of 100 patients) with knee OA (mean age 62,6±7,1), with Kelgren and Lawrence radiograhic grade II-III, pain >40mm at a 100mm visual analog scale (VAS) were studied. WOMAC and EQ-5D questionnairies, and “stand up and go” test were served as criteria of treatment efficacy. Results There was no difference between groups regarding baseline characteristics. The significant decrease of pain and joint function improvement was observed in both groups after the first month of each treatment. This was maintained during the whole period of the follow-up. Significant decrease in stiffness was observed after one month of Aceclofenac and after two months of Diclofenac treatments. Significant improvement of general health and EQ-5D questionnaire results as well as decreased “stand up and go” test accomplishment time were observed in both groups after one month of treatment. After the first month significant “improvement” was observed in 86.3% in Aceclofenac patients and in 66% patients from Diclofenac group and after three month of treatment, in 95.8% and 76.2% patients, respectively (p Conclusions Our results show that both drugs were effective in the treatment of OA. Rceclofenac is capable of decreasing pain faster than Diclofenac. In addition Rceclofenac use is associated with a decreased risk of gastroenterological side effects. Disclosure of Interest None Declared