[The burden of COVID-19 in a heterogeneous population of immunocompromised patients - realities of the postpandemic].

On July 3, 2023, an interdisciplinary Council of Experts "The burden of COVID-19 in a heterogeneous population of immunocompromised patients - post-pandemic realities" was held in Moscow with leading experts in pulmonology, rheumatology, hematology, oncology, nephrology, allergology-immunology, transplantation, and infectious diseases. The aim of the meeting was to discuss the current clinical and epidemiologic situation related to COVID-19, the relevance of disease prevention strategies for high-risk patients. The experts addressed the following issues: 1) the disease burden of COVID-19 in 2023 for patients with immunodeficiency in different therapeutic areas; 2) the place of passive immunization with monoclonal antibodies as a method of COVID-19 prophylaxis among immunocompromised patients; 3) prerequisites for the inclusion of passive immunization of immunocompromised patients into routine clinical practice.

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

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

Global Antiphospholipid Syndrome Score (GAPSS) in Patients with Systemic Lupus Erythematosus.

The Global Antiphospholipid Syndrome Score (GAPSS) is a tool proposed to quantify the risk of clinical manifestations associated with antiphospholipid antibodies (aPL) and certain cardiovascular risk factors. To validate GAPSS in a cohort of patients with systemic lupus erythematosus in Russia. 115 patients with SLE were included in the study, including 51 (44%) patients with systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), 14 (12%) SLE patients with aPL, and 50 (44%) patients with SLE. There was a history of thrombosis in 58 (50%) out of 115 patients; of them, 14 (24%) had arterial thrombosis, 29 (50%) had venous thrombosis, and 15 (26%) had combined thrombosis. Pregnancy against the background of the disease occurred in 43 women included in the study. Of them, 29 (67%) had obstetric pathology. Patients with thrombosis and obstetric pathology had a GAPSS score of 7.17 ± 5.64 versus 4.48 ± 4.55 without these manifestations (p = 0.0003). There was a significant association between GAPSS levels and thrombosis: patients with thrombosis had a GAPSS of 7.31 ± 5.70, those without thrombosis-4.00 ± 4.81 (p = 0.001). GAPPS values were higher in arterial thrombosis compared to venous thrombosis (10.40 ± 25.30 versus 5.82 ± 5.28, p = 0.01). GAPSS levels  ≥ 6 and  ≥10 were analyzed to select GAPSS values at which a high risk of recurrent thrombosis and/or obstetric pathology could be indicated. All GAPSS levels had a significant association with clinical manifestations of APS. The quality of GAPSS by ROC analysis showed an area under the curve (AUC) for GAPSS of 0.697. GAPSS can be used to assess the risk of recurrence or development of thrombosis and/or obstetric pathology in patients with SLE in the Russian Federation. The GAPSS ≥6 values should be used to stratify patients with SLE into high risk group for recurrence of vascular complications. Further prospective follow-up is needed to confirm the value of GAPSS.

Antibodies to Domain I ß2-Glycoprotein 1 in Patients with Antiphospholipid Syndrome and Systemic Lupus Erythematosus.

The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of ß2-glycoprotein 1 (ß2-GP1), IgG anti-ß2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-ß2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-ß2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-ß2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-ß2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-ß2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-ß2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-ß2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-ß2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-ß2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-ß2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-ß2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively).

[Impact of surgical treatment of morbid obesity on joint diseases].

The prevalence of obesity in the modern world is increasing. Obesity is an independent risk factor for some rheumatic diseases and also worsens their course. The presence of chronic joint disease can make it difficult for obesity to reduce activity, creating a vicious circle where joint pain makes exercise difficult and being overweight exacerbates joint pain. At the same time, there is a conditionally radical method of treating obesity - bariatric surgery (BS), which is currently used when conservative methods are ineffective. The purpose of this review is to analyze the data presented in the world literature on the impact of BS on the course of the most common rheumatic diseases. The available data show the possibility of a positive effect of BS not only on weight loss, but also on the course of a number of rheumatic diseases.

Metal-Organic Frameworks and Their Biodegradable Composites for Controlled Delivery of Antimicrobial Drugs.

Antimicrobial resistance (AMR) is a growing global crisis with an increasing number of untreatable or exceedingly difficult-to-treat bacterial infections, due to their growing resistance to existing drugs. It is predicted that AMR will be the leading cause of death by 2050. In addition to ongoing efforts on preventive strategies and infection control, there is ongoing research towards the development of novel vaccines, antimicrobial agents, and optimised diagnostic practices to address AMR. However, developing new therapeutic agents and medicines can be a lengthy process. Therefore, there is a parallel ongoing worldwide effort to develop materials for optimised drug delivery to improve efficacy and minimise AMR. Examples of such materials include functionalisation of surfaces so that they can become self-disinfecting or non-fouling, and the development of nanoparticles with promising antimicrobial properties attributed to their ability to damage numerous essential components of pathogens. A relatively new class of materials, metal-organic frameworks (MOFs), is also being investigated for their ability to act as carriers of antimicrobial agents, because of their ultrahigh porosity and modular structures, which can be engineered to control the delivery mechanism of loaded drugs. Biodegradable polymers have also been found to show promising applications as antimicrobial carriers; and, recently, several studies have been reported on delivery of antimicrobial drugs using composites of MOF and biodegradable polymers. This review article reflects on MOFs and polymer-MOF composites, as carriers and delivery agents of antimicrobial drugs, that have been studied recently, and provides an overview of the state of the art in this highly topical area of research.

Metal-Organic Frameworks as Potential Agents for Extraction and Delivery of Pesticides and Agrochemicals.

Pesticide contamination is a global issue, affecting nearly 44% of the global farming population, and disproportionately affecting farmers and agricultural workers in developing countries. Despite this, global pesticide usage is on the rise, with the growing demand of global food production with increasing population. Different types of porous materials, such as carbon and zeolites, have been explored for the remediation of pesticides from the environment. However, there are some limitations with these materials, especially due to lack of functional groups and relatively modest surface areas. In this regard, metal-organic frameworks (MOFs) provide us with a better alternative to conventionally used porous materials due to their versatile and highly porous structure. Recently, a number of MOFs have been studied for the extraction of pesticides from the environment as well as for targeted and controlled release of agrochemicals. Different types of pesticides and conditions have been investigated, and MOFs have proved their potential in agricultural applications. In this review, the latest studies on delivery and extraction of pesticides using MOFs are systematically reviewed, along with some recent studies on greener ways of pest control through the slow release of chemical compounds from MOF composites. Finally, we present our insights into the key issues concerning the development and translational applications of using MOFs for targeted delivery and pesticide control.

[Antibodies to the phosphatidylserine/prothrombin complex in the diagnosis of antiphospholipid syndrome].

AIM: To determine the significance of antibodies to the phosphatidylserine/prothrombin complex (aPS/PT) in patients with systemic lupus erythematosus (SLE) antiphospholipid syndrome (APS). MATERIALS AND METHODS: A total of 190 patients were included in the study: 123 (64.7%) with reliable SLE and 55 (29%) with PAPS. The control group included 100 relatively healthy subjects of comparable age. All patients were tested for classical aPL as well as IgG/IgM-anti-PS/PT by enzyme immunoassay. RESULTS: Based on the average values of IgG/IgM aPS/PT of the control group, the levels of positivity were allocated mean (M) + 3 or 5 standard deviations (SD): M+3SD and M+5SD. IgG aPS/PT levels above 73.6 U/ml (M+5SD) were more accurate diagnostic, for IgM aPS/PT above 18.0 U/ml. IgG-aPS/PT were detected in 84 (44%) of 190 patients. Levels above diagnostic levels were detected in 68 (65%) of 104 patients with APS (55 with PAPS and 59 with SLE+APS). Thrombosis was significantly more common in patients with IgG aPS/PT compared with patients negative for IgG aPS/PT. Arterial but not venous thrombosis was associated with IgG aPS/PT positivity. CONCLUSION: The frequency of detection of IgG aPS/PT in the examined patients was 44%, IgM aPS/PT 29% and their combination 19% of 190 patients. Half of the patients with probable APS had positive IgG aPS/PT and third IgM aPS/PT. Median IgG aPS/PT were significantly higher in patients with APS compared to patients without APS and the control group. Thrombosis was associated with IgG aPS/PT. Arterial thrombosis was significantly more frequently reported in patients with IgG aPS/PT. The sensitivity of IgG aPS/PT for reliable APS at levels greater than 73.6 units/ml was 59%, specificity 92%, for IgM aPS/PT 35% and 91%, respectively.

[Epithelial protective therapy in comorbid diseases. Practical Guidelines for Physicians].

This document was produced with the support of the National Medical Association for the Study of Comorbidities (NASС). In 2021 the first multidisciplinary National Consensus on the pathophysiological and clinical aspects of Increased Epithelial Permeability Syndrome was published. The proposed guidelines are developed on the basis of this Consensus, by the same team of experts. Twenty-eight Practical Guidelines for Physicians statements were adopted by the Expert Council using the "delphic" method. Such main groups of epithelial protective drugs as proton pump inhibitors, bismuth drugs and probiotics are discussed in these Guidelines from the positions of evidence-based medicine. The clinical and pharmacological characteristics of such a universal epithelial protector as rebamipide, acting at the preepithelial, epithelial and subepithelial levels, throughout gastrointestinal tract, are presented in detail.

Coronavirus Infection 2019 (COVID-19) and Autoimmunity.

The pandemic of coronavirus disease 2019, etiologically associated with the SARS-CoV-2 virus, has drawn the attention of the medical community to new clinical and fundamental problems in the immunopathology of human diseases. During a detailed analysis of the clinical manifestations and immunopathological disorders in COVID-19, it became apparent that SARS-CoV-2 infection is accompanied by the development of a wide range of extrapulmonary clinical and laboratory disorders, some of which are characteristic of immunoinflammatory rheumatic diseases and other human autoimmune and autoinflammatory diseases. All this taken together served as a theoretical justification for the repositioning of anti-inflammatory drugs in COVID-19, previously specifically designed for the treatment of immunoinflammatory rheumatic diseases. The prospects for studying the autoimmune mechanisms of COVID-19 and the possibility of anti-inflammatory therapy are discussed.

Zirconium-Based MOFs and Their Biodegradable Polymer Composites for Controlled and Sustainable Delivery of Herbicides.

Adsorption and controlled release of agrochemicals has been studied widely using different nanomaterials and a variety of formulations. However, the potential for application of high surface-area metal-organic frameworks (MOFs) for the controlled release of agrochemicals has not been thoroughly explored. Herein, we report controlled and sustainable release of a widely used herbicide (2-methyl-4-chlorophenoxyacetic acid, MCPA) via incorporation in a range of zirconium-based MOFs and their biodegradable polymer composites. Three Zr-based MOFs, viz., UiO-66, UiO-66-NH2, and UiO-67 were loaded with MCPA either postsynthetically or in situ during synthesis of the MOFs. The MCPA-loaded MOFs were then incorporated into a biodegradable polycaprolactone (PCL) composite membrane. All three MOFs and their PCL composites were thoroughly characterized using FT-IR, TGA, SEM, PXRD, BET, and mass spectrometry. Release of MCPA from each of these MOFs and their PCL composites was then studied in both distilled water and in ethanol for up to 72 h using HPLC. The best performance for MCPA release was observed for the postsynthetically loaded MOFs, with PS-MCPA@UiO-66-NH2 showing the highest MCPA concentrations in ethanol and water of 0.056 and 0.037 mg/mL, respectively. Enhanced release of MCPA was observed in distilled water when the MOFs were incorporated in PCL. The concentrations of herbicides in the release studies provide us with a range of inhibitory concentrations that can be utilized depending on the crop, making this class of composite materials a promising new route for future agricultural applications.

Study of antiphospholipid antibodies by enzyme immunoassay and chemiluminescent methods in patients with antiphospholipid syndrome and systemic lupus erythematosus (preliminary data).

Antiphospholipid antibodies (aPL) are a family of different autoantibodies that lead to recurrent vascular thrombosis of any localization and caliber, and/or obstetric pathology - fetal loss. Serological markers of antiphospholipid syndrome (APS) include only three types of aPL - lupus anticoagulant (VA), antibodies to cardiolipin (aCL) classes IgG and IgM, antibodies to ß2-glycoprotein1 (aß2GP1) classes IgG and IgM. Medium and high levels of aCL and aß2HP1 (IgG and / or IgM) were selected as serological markers of APS in the 2006 classification criteria. However, the threshold of values used from low to moderately high levels has not been standardized. aPL standardization issues are still unresolved, resulting in heterogeneous results of the ongoing studies. The aim of the study was to assess the comparability IgG/IgM-aCL and IgG/IgM-ab2GP1 by enzyme-linked immunosorbent assay and chemiluminescent analysis in patients with APS with and without (systemic lupus erythematosus) SLE. The study included 70 patients (49 women and 21 men) with APS, of which 21 (30%) were with primary APS (pAPS) and 49 (70%) with APS in combination with SLE. All study participants underwent determination of IgG/IgM-aCL and IgG/IgM-aß2GP1 by enzyme-linked immunosorbent. A study was performed by the chemiluminescent analysis: IgG/IgM-aCL - in 70 patients; IgG/IgM-aß2GP1 - in 69 patients. Results. According to preliminary data, the determination of IgG-aCL and IgG-aß2GP1 by the chemiluminescent analysis is informative in assessing positivity according to the manufacturer, compared with the enzyme-linked immunosorbent (p < 0.05). However, when taking into account the levels of antibody positivity determined by enzyme-linked immunosorbent, the level of positive values according to chemiluminescent analysis was much higher than the performance of the manufacturer.

[Application of cardiovascular risk scales to identify carotid atherosclerosis in patients with rheumatoid arthritis].

AIM: To evaluate the cardiovascular risk (CVR) and analyze its relationship with detection of early carotid artery atherosclerotic lesion in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: One hundred and nine RA patients aged 45 to 60 without established cardiovascular diseases (CVD) were included in the study. The median age was 52 [48; 54] years, duration of RA was 120 [36; 204] months, DAS28 was 4.7 [3.5; 5.6] points. CVD risk was calculated with mSCORE, Reynolds Risk Score (RRS), ASSIGN, QRISK3, ERS-RA scales and Carotid Artery Doppler Ultrasound Exam was performed for all patients. RESULTS: High risk was found in 5, 5, 14, 6, and 38% of patients according to mSCORE, RRS, ASSIGN, QRISK3, ERS-RA scales, respectively. Atherosclerotic plaques of carotid arteries were found in 30% of patients. It was found that carotid intima-media thickness is correlated to all CVR calculators, age, systolic and diastolic blood pressure, cholesterol, erythrocyte sedimentation rate, interleukin-6 levels. The sensitivity and specificity of the CVR algorithms in prognostication of atherosclerotic carotid artery lesions were 73 and 67% for mSCORE, 64 and 63% for RRS, 64 and 56% for ASSIGN, 73 and 49% for QRISK3, respectively, p0.05 in all cases, 67 and 50% for ERS-RA, p=0.06. CONCLUSION: RRS, mSCORE, ASSIGN, QRISK3 calculators equally predict atherosclerotic carotid artery damage in RA patients. The optimal ratio of specificity and sensitivity is shown for the mSCORE scale. Stratification of CVR in RA patients should include assessment of the carotid intima-media thickness. To identify CVR in RA patients, the most informative methods are mSCORE calculation and carotid intima-media thickness determination.

[Efficacy of combined use of glycosaminoglycan peptide complex for intramuscular administration and oral diacerein in osteoarthritis: evaluation according to an observational multicenter clinical trial].

BACKGROUND: The combined use of intramuscular injection glycosaminoglycan peptide complex (GPC) and oral diacerein can increase the effectiveness of treatment of osteoarthritis (OA). AIM: Compare the effectiveness of combination GPC + diacerein and GPC monotherapy in the treatment of OA in clinical practice. MATERIALS AND METHODS: A retrospective evaluation of the results of a 12-week multicenter observational non-interventional study of the effectiveness of GPC (Rumalon, a course of intramuscular injections 3 times a week, №25) in patients with moderate/severe OA (n=2955) requiring regular administration of nonsteroidal anti-inflammatory drugs (NSAIDs). The analysis identified a group of patients (n=414) who received GPC in combination with diacerein 100 mg/day (Diaflex Rompharm). The therapeutic effect was compared in the groups of GPC monotherapy (n=2541) and the combination of GPC with diacerein. These groups did not differ in average age (61.411.8 and 61.911.3 years), both were dominated by women (76.3 and 70.3%), there was approximately equal intensity of pain during movement and impaired joint function: 6.11.8/6.01.6 and 4.92.1/5.11.8 (according to the numerical rating scale 010). The dynamics of pain intensity, the need for NSAIDs, and the frequency of adverse events (AE) were compared 12 weeks after the start of treatment. RESULTS AND DISCUSSION: In the majority of patients with OA both on the background of GPC monotherapy and combined use of GPC and diacerein, there was a significant improvement. The number of patients with pain reduction 50% was 54.3 and 62.8% (p0.001), NSAID administration was completely stopped in 66.7 and 77.5% (p0.001), respectively. The effectiveness of the combination of GPC and diacerein was significantly higher than that of GPC monotherapy in OA of the knee joint, hip joint, and generalized OA. AE from the gastrointestinal tract was observed in 7.8 and 8.9%, arterial hypertension in 6.3 and 4.6%, allergic reactions in 0.3 and 0.5% of patients (not significant). CONCLUSION: The application of the code of civil procedure is an effective treatment for OA. The combination of GPC and diacerein provides a more significant improvement than GPC monotherapy. GPC and diacerein (including in combination) are well tolerated and rarely cause AE.

[Locomotive syndrome: from paradigms to clinical reality].

Locomotive syndrome is an unsatisfactory condition of patients over 60 years of age who need or may require outside help in the near future due to functional deterioration of the musculoskeletal system, including pathology of bone tissue, joints, muscles and nervous tissue. In real clinical practice, one often has to deal with the following manifestations of locomotive syndrome: osteoarthritis, sarcopenia, balance disorders, chronic musculoskeletal pain. Today, there is a clear understanding that drug therapy should be long-term, include comprehensive support for muscle tissue, balance training, and mandatory cognitive-behavioral therapy. Maximum safety of long-term drug therapy can be ensured by the use of vital micronutrients, which include highly purified forms of chondroitin sulfate and glucosamine sulfate, which have a wide range of anti-inflammatory and regenerative effects.

Pharmacological Management of Osteoarthritis With a Focus on Symptomatic Slow-Acting Drugs: Recommendations From Leading Russian Experts.

BACKGROUND: This article describes an updated stepwise algorithm for the pharmacological management of osteoarthritis (OA) to establish a treatment method for patients with OA. SUMMARY: In step 1, background maintenance therapy includes symptomatic slow-acting drugs for OA, especially prescription crystalline glucosamine sulfate product, for which the high-quality evidence base of efficacy is unequivocal, or prescription chondroitin sulfate. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) or paracetamol only as rescue analgesia is given on top of the background therapy. Step 2: For patients with persistent OA symptoms, the use of oral NSAIDs is mandatory for maintaining supportive therapy with symptomatic slow-acting drugs for OA. It is recommended to properly stratify patients and carefully select oral NSAID therapy to maximize the benefit-to-risk ratio. Intra-articular hyaluronic acid and intra-articular corticosteroids are recommended as well in step 2 of the algorithm, especially for patients who do not respond to the previous therapies. Step 3: Duloxetine is considered along with the previous procedures, especially in patients with pain from central sensitization. Step 4: Total joint replacement is recommended for patients with severe symptoms and poor quality of life. MAJOR CONCLUSIONS: The current guidelines and literature review provide evidence-based recommendations supported by clinical experience on how to organize the treatment process in patients with knee OA applicable in the Russian clinical practice. FUTURE RESEARCH DIRECTIONS: International evidence-based guidelines lack consensus on different treatments, including the use of prescription crystalline glucosamine sulfate, NSAIDs, and intra-articular hyaluronic acid. The content of this article needs a further discussion about the clinical evidence and harmonization of recommendations for knee OA management.

[The efficacy and safety of intra-articular application of a combination of sodium hyaluronate and chondroitin sulfate for osteoarthritis of the knee: a multicenter prospective study].

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.