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Objective: to investigate the efficacy of Alflutop therapy in patients with knee osteoarthritis (OA) with or without concomitant diseases. Material and methods. The large-scale, multicenter prospective, open-label, observational, non-interventional ISKRA study (Study: Prescribing the drug Alflutop, solution for injection, for OA in real world clinical practice) included 22,525 patients, 10,616 of whom had knee OA. The mean age of patients with knee OA was 60.1±11.7 years, body mass index (BMI) was 28±4.6 kg/m2 , and median disease duration was 60 [24; 120] months. All patients had significant comorbidities: arterial hypertension in 90% of cases, and ischemic heart disease, diabetes mellitus and obesity in one in three cases. Alflutop was administered daily 1 ml intramuscularly (IM), No. 20, or every second day 2 ml IM, No. 10. The efficacy of the treatment was assessed by the dynamics of pain intensity using a visual analogue scale (VAS), patient's general health assessment (PHA) using VAS and quality of life using EQ-5D, and the need for non-steroidal anti-inflammatory drugs (NSAIDs). Results and discussion. After one course of treatment, median pain intensity decreased from 60 [40; 70] to 20 [10; 40] mm, quality of life improved – median EQ-5D increased from 0.59 [0.36; 0.69] to 0.85 [0.73; 1]) and PHA from 50 [37; 70] to 80 [60; 90] mm, and the need for NSAIDs decreased. Female gender, older age, high BMI, severe pain, radiological stages III and IV, poorer quality of life, presence of concomitant diseases and lower adherence to treatment were associated with a less significant response to therapy. Conclusion. The results of the use of Alflutop in knee OA suggest that widespread use in real-life clinical practice is possible. The inclusion of additional therapeutic targets in the OA treatment strategy, as well as the identification and correction of factors associated with a less pronounced analgesic effect of the drug, will potentially improve treatment efficacy.

The aim of the study – to evaluate the effectiveness of the drug Alflutop (bioactive concentrate of small marine fish), as well as its effect on microcirculation parameters in patients with osteoarthritis (OA) of small joints of the hands.Patients and methods. The study included 80 patients aged 35 to 65 years with OA of small joints of the hands, stage I– II according to Kellgren – Lawrence, with pain ≥40 mm and ≤90 mm on a visual analogue scale (VAS). Subjects were distributed in 1:1 ratio. In the study group (combined therapy) patients received Alflutop according to the standard scheme: 2 ml intramuscularly every other day N 10 and meloxicam 7.5–15 mg per day in the “on demand” mode. The second group (monotherapy) received meloxicam 7.5–15 mg per day N 20. During the observation, the dynamics of joint pain on the VAS scale, the dynamics of the disease on the VAS scale by the patient and the doctor, the functional Dreiser index and AUSCAN (Australian/Canadian Osteoarthritis Hand Index), nailfold capillaroscopy (NFC) with an assessment of the number of capillaries and the number of alterations per 1 mm of the distal row of capillaries were evaluated. The duration of the study was 6 weeks.Results and discussion. By the 35th day of treatment with Alflutop in combination with meloxicam, a statistically significant decrease in pain and functional activity of the disease was found according to the VAS indices, the AUSCAN index (p0.05). In meloxicam monotherapy group, by the 35th day of follow-up, there was a significant increase in the number of altered capillaries by 1 mm of the distal row of the nail (p

Back pain constitutes one of the major medico-social problems of healthcare. The development of a unified approach to the diagnosis and treatment of back pain is hindered since it is difficult to assess the various approaches to its treatment, especially its chronic forms. Yet recent data witnessing the important role of the neuroinflammatory process in the pathogenesis of the degenerative forms of discopathy suggest that the traditional treatment approach, which includes physical therapy exercises and non-steroidal anti-inflammatory drugs and myorelaxants, could be enhanced by using drugs characterized by slow structure-modifying action on the structure of the cartilaginous tissue of intervertebral discs and joints. Given the intelligent use of manual therapy, needle reflex therapy, kinesiotherapy, as well as modification of psychosocial factors that pre-determine the yellow flag phenomenon, the application of sustained-release symptomatic drugs increases the efficacy of therapy and prevents subsequent pain episodes. As of today, a placebo-controlled study has proven the action of Alflutop, which can be administered both intramuscularly and paravertebrally. This approach not only improves the patients’ condition but also reduces the burden associated with chronic back pain problems for the society.

Osteoarthritis (OA) is one of the most important medical and social problems due to the steady increase in morbidity and disability. Prevention, management of risk factors, and early treatment of OA are critical.Objective of the ISKRA study was to evaluate the efficacy of Alflutop in patients with OA of different locations and/or low back pain (LBP) with or without concomitant diseases.Material and methods. We selected 11,136 patients with OA of specific localizations aged 50 to 72 years. The duration of the study ranged from 20 to 31 days, and the number of visits was 2 (B1 and B2). Alflutop was prescribed 1 ml intramuscularly (IM) daily No. 20 or 2 ml IM every other day No. 10.The efficacy of therapy was determined by the time of onset of clinical effect (pain reduction, as assessed by the patient), the dynamics of pain intensity in the studied joint during movement and/or LBP according to the visual analogue scale (VAS), the assessment of quality of life according to the EQ-5D questionnaire and the patient's general health status (PGH) according to VAS. We assessed treatment adherence, need for nonsteroidal anti-inflammatory drugs (NSAIDs), satisfaction with treatment (based on VAS). The presence of comorbidities was also considered.Results and discussion. In hand OA (n=2776), a positive effect of therapy was observed in 98.6% of cases, according to patients' assessment. During the course of therapy, there was a significant decrease in pain on movement in the hands (according to VAS), improvement in PGH and quality of life (according to EQ-5D). Rapid development of the analgesic effect was seen on average at day 9.In hip OA (n=6666), a decrease in pain was noted in 83.3% of cases (

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.

Back pain (BP) is a major public health problem worldwide with high prevalence and disability. In most cases are associated with degenerative spinal disease (degenerative disc disease, DDD), myofascial syndrome, facet joint syndrome, spinal spondylosis, scoliotic deformation, sacroilial joint dysfunction, lumbar stenosis and other causes. The article describes the basics of the doctor’s approach to the diagnosis of back pain, describes the main strategies of patients routing. The algorithm proposed here includes detection of dangerous conditions, verification of inflammatory rhythm of BP according to criteria ASAS 2009, revealing of persistent phenotype of the lower back pain, stratifying patients for the risk of chronic lower back pain StarT Back in mechanical rhythm; multidisciplinary approach with inclusion of the rheumatologist in specialists team, and after initial consultation the therapist gives direction to the rheumatologist, if necessary. A therapist who treats a patient with persistent BS and a high risk of chronization without symptoms of “red flags” should prescribe an magnetic resonance imaging of the spine. The detection of total lesion of the vertebral motor segments in the case of severe back pain is the basis for the diagnosis of spinal osteoarthritis and subsequent prescription of non-medicamentous and pharmacological therapy, including SYSADOA, in particular Alflutop. The developed algorithm allows to quickly diagnose spinal osteoarthritis at a young age and to suspect axial spondylitis. Presented triad of MR-traits associated with persistent phenotype pain, which will help the therapist to establish the diagnosis of spinal osteoarthritis. The algorithm clearly describes the routing of patients to related specialists (rheumatologist, neurologist, etc.) according to the identified data.

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.

Objective: to evaluate efficacy and safety of the use of a bioactive concentrate of small marine fish (Alflutop) in patients with vertebrogenic sciatica (SC).Patients and methods. The study included 30 patients with persistent (more than 3 months) vetebrogenic SC who underwent inpatient treatment in the neurological department of the Republican Clinical Neurological Center (Kazan). The patients were randomized into two groups: 15 patients of the 1st group received Alflutop (2 ml intramuscularly every other day, 10 injections in total) in addition to standard therapy, and 15 patients of the 2nd group (control) received standard therapy. The effectiveness of therapy was assessed using a visual analogue scale, Roland-Morris and EQ-5D questionnaires, an index of severity and frequency of sciatica.Results and discussion. Patients who received the study drug in addition to standard therapy showed a more rapid decrease in pain intensity, a trend towards a decrease in the severity index of sciatica, while no adverse events were recorded during the entire follow-up.Conclusion. The inclusion of Alflutop in the traditional scheme of inpatient treatment of patients with vertebrogenic SC allows to achieve a significantly greater reduction in the intensity of the pain syndrome after 20 days and 2 months after the start of therapy.

The new coronavirus infection (COVID-19) is associated with a wide spectrum of various clinical manifestations including involvement of the musculoskeletal system which can persist for a long time after the infection. Supposedly, pathogenesis of musculoskeletal manifestations of COVID-19 is primarily caused by systemic inflammation accompanied by cytokine hyperexpression (interferon γ, interleukins 1β, 6, 8, 17, tumor necrosis factor α), as well as hypoxia leading to overproduction of inflammatory cytokines, activation of bone reabsorption by osteoclasts and subsequent decrease of mineral bone density and osteonecrosis in some cases. Additionally, some drugs prescribed to patients with COVID-19 (some antiviral drugs and glucocorticoids) should also be taken into account as they can lead to development of musculoskeletal pathology. In the acute period of COVID-19, myalgias are common, but in rare cases myositis with proximal muscular weakness and increased levels of creatine phosphokinase, lactate dehydrogenase can occur. Arthralgias in the acute period of COVID-19 are rarer than myalgias. In the studies of clinical manifestation of COVID-19, frequency of arthralgias and myalgias in the acute period is between 15.5 and 50 %. After COVID-19, frequency of arthralgias and myalgias gradually decreases, however there are cases of long-term joint and muscle pains, as well as post-viral arthritis, development of arthritis in the context of various autoimmune disorders. Myalgias and arthralgias during COVID-19 usually regress spontaneously and in most patients do not require prescription of antipain medications, but in some cases pain management is necessary. Use of non-steroid anti-inflammatory drugs and vitamin D during COVID-19 is a safe and effective method of pain management, including myalgia and arthralgia. Rehabilitation programs play an important role in improvement of functional state and patient recovery after moderate and severe COVID-19.

The review presents an analysis of the therapeutic effect in osteoarthritis (OA) of the original complex injectable drug Alflutop (bioactive concentrate of small marine fish), which is one of the most widely used symptomatic slow acting drugs (SYSADOA) in Russia. It stimulates the proliferation of chondrocytes, activates the synthesis of the extracellular matrix by modulating transforming growth factor β (TGFβ), inhibits hyaluronidase, oxidative stress and the activity of extracellular expression of proinflammatory cytokine genes – interleukin (IL) 1β, IL6 and IL8 in vitro.The results of prospective clinical studies are presented, which demonstrate the ability of Alflutop to slow down the X-ray progression of OA of the knee joints (inhibit the narrowing of the joint space, the growth of osteophytes and increase the intra-articular concentration of hyaluronic acid), as well as restore the mobility of the hip joints when it is locally introduced into the zone of pathological changes in the articular lip of the acetabulum. Combined therapy with Alflutop leads to activation of reparative processes and significant clinical improvement in patients with post-traumatic OA, and also slows down the progression of chondrodegeneration according to magnetic resonance imaging. The new Alflutop administration regimen for knee OA (2 ml every other day, №10) can increase patient adherence to therapy.The results of clinical studies presented in the review prove the structural-modifying effect of Alflutop in OA of various localization and substantiate its widespread use in this disease in rheumatological, traumatological and orthopedic practice.

Objective: to evaluate the efficacy and safety of Alflutop therapy in elderly patients (75–90 years old) with knee osteoarthritis (OA) and multimorbidity based on the results of a prospective 6-year follow-up.Patients and methods. The study included 38 elderly women with knee OA (according to ACR criteria, 1986) stage II–III by Kellgren–Lawrence grading system, with pain ≥40 mm by visual analogue scale (VAS), who needed to take non-steroidal anti-inflammatory drugs (NSAIDs). Alflutop was administered as 1 ml intramuscular injections 20 consecutive days with a 6-month interval (12 courses). The effectiveness of therapy was assessed by VAS, WOMAC index and EQ-5D questionnaire. The safety of therapy was monitored throughout the observation period. The duration of the study was 6 years.Results and discussion. The full course of treatment with Alflutop was completed by 29 (76.3%) patients. Nine (23.7%) patients discontinued the study due to their inability to visit the treatment center (for reasons unrelated to the study).In elderly patients with knee OA, high level of multimorbidity was revealed, 5 comorbidities on average.There was a significant decrease in pain according to VAS (≥20%): by visit (V) 1 – in 76.3%, by V2 – in 71.0%, by V3 – in 68.4%, by V4 – in 63.1% and by V5 – in 55.2% of patients. By the 21st day of Alflutop therapy, a statistically significant decrease in the total WOMAC index (p

Objective: to evaluate the efficacy and safety of Alflutop (the bioactive concentrate from small sea fish) in patients aged 75 years and older with knee osteoarthritis (OA). Patients and methods. The investigation enrolled 38 patients aged 75 years and older with knee OA (according to the American College of Rheumatology (ACR) criteria, 1986), Kellgren–Lawrence grades II–III, ≥40 mm pain visual analogue scale (VAS), who required continuous non-steroidal anti-inflammatory drug (NSAID) use. All the patients received Alflutop in the standard regimen: a 1-ml intramuscular injection daily for 20 days. The dynamics of pain during movement was assessed using the VAS scale, the WOMAC, and the EQ-5D questionnaire. Comorbidity was determined according to the Charlson comorbidity index, polypharmacy, and the safety of therapy in all the patients. The investigation duration was 8 weeks.Results and discussion. On day 21 of Alflutop therapy, there was a statistically significant reduction in pain, stiffness, and functional insufficiency according to the WOMAC index (p< 0.001) and improvements in quality of life as shown by the EQ-5D questionnaire (p< 0.001); on day 56, the number of NSAID intake days decreased (p=0.005). The findings suggest that there is a high level of comorbidity in the majority (94.7%) of patients. The mean number of drugs taken was 5.0±1.5, which indicates the presence of polypharmacy. No serious or severe adverse events were recorded.Conclusion. The results of the investigation showed the statistically significant efficacy and safety of Alflutop in patients with knee OA in the elderly group.

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 (p

Currently, with osteoarthritis (OA), numerous over-the-counter and prescription drugs are used, as well as biologically active additives (BAA). Significant market share in Russia are: chondroitin sulfate, glycosaminoglycan-peptide complex and Alflutop.The purpose of the article is to compare the clinical recommendations of the professional communities of doctors of the Russian Federation, countries of Europe, Great Britain, the USA, Canada, Australia on approaches to chondroprotective therapy/SYSADOA for osteoarthritis using the example of chondroitin sulfate, glycosamine glycan-peptide complex and Alflutop.Materials and methods: The analysis included 11 clinical recommendations (guideline) from 2008 to 2019 on the management of patients with OA.Results: The glycosaminoglycan-peptide complex (Rumalon) and Alflutop were recommended by the Russian Scientific Medical Society of Therapists (RNMOT), but are not mentioned in the recommendations of several Russian professional communities. In the European recommendations, the glycosaminoglycan-peptide complex and the drug Alflutop are not considered. Chondroitin sulfate to reduce the symptoms of OA is recommended by 5 professional guideline. With the exception of Russian recommendations, the listed professional communities recommend the use of chondroitin sulfate only as a “pharmaceutical quality drug”.Conclusion: It is advisable to agree on Russian recommendations on the use of the drugs in question. At the level of foreign and Russian professional communities, particular attention is required to analysis of data on the use of chondroitin sulfate, taking into account the quality of production, the composition of active substances and bioavailability, the quantitative content of active substances and the quality of substances. It is necessary to systematize the products with a separate assessment of the effectiveness of registered medicines, biologically active additives of pharmaceutical quality and low-quality products with minimal bioavailability.

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).

Introduction: the article describes the most common variants of paraarticular tissue pathology (PTP) - enthesitis of the upper and lower extremities, back. The issues of enthesitis etiology, pathogenesis, clinic presentation, diagnosis, differential diagnosis are considered. The historical background, technique and mechanism of action of perifocal syringe injections are presented.Objective of the study: evaluate the clinical efficacy of perifocal syringe injection of Alflutop in patients with enthesitis of the upper and lower extremities and back.Materials and methods of the study: 76 patients with shoulder joint enthesitis (30 patients), epicondylitis (10), back pain (14), trochanteritis (13), anseritis of the knee joints (9) received treatment with perifocal injections of Alflutop as a course of 5 injections with an interval of 1 injection every 2 -3 days. We evaluated general well-being, local pain at rest, during palpation and movement, range of motion. The diagnosis was established clinically, and using the results of x-ray examination, ultrasound, MRI.The results of treatment: significant outcomes in patients, which included improved well-being, reduced pain, increased range of motion. 69 of 76 patients demonstrated significant improvement and improvement - the effectiveness of therapy was 90.8% with high tolerability of the drug.

The paper discusses the etiology, pathogenesis, pathomorphology and pathophysiology of osteoarthritis of large joints from the perspective of evidencebased medicine. The processes occurring in the tissues of the joints during the development of the pathological process at various stages are described in detail; the features of diagnosis and treatment in sports medicine are described in detail. The characteristic of drugs used to treat osteoarthritis is described, with a description of the positive effect and negative effect on particular organs and systems. A preparation Alflutop was comprehensively analysed regarding its effectiveness in terms of safety and impact on the development of the pathological process. It was shown that Alflutop is a drug of choice in the treatment of joint destruction.

The article presents the results of a study of the effect of prolonged Alflutop therapy on the arthrosonographic changes in knee joints (sizes of articular cartilage, joint space width, severity of osteophytic disease, local inflammation activity) in patients with gonarthritis. The treatment was prescribed to patients in the early stages of the disease and repeated by regular courses. It was found that prolonged therapy with Alflutop slows down the articular cartilage degradation, the progression of structural changes in knee joints, the local inflammation activity (according to arthrosonography), which reduces the symptoms of osteoarthritis and improves the patient’s quality of life.

The article presents the results of a study investigating the effect of prolonged treatment with Alflutop (5-year follow-up) on the radiographic progression of knee osteoarthritis (narrowing of the height of the X-ray articular cavity, osteophytosis, worsening of the radiographic stage of the pathological process). Medication was prescribed to 64 patients (mean age of 47.4 ± 11.6 years) at the early stages of the disease and was carried out by repeated courses. The comparison group consisted of 140 patients (mean age of 46.7 ± 10.4 years). It was noted that long-term treatment with Alflutop slows the progression of structural changes of the knee, which certainly has a positive effect on symptoms of osteoarthritis, the quality of life of patients.

The article discusses experimental data that demonstrated the ability of Aflutop to stimulate proliferation and regeneration of chondrocytes, to inhibate in vitro extracellular release of IL-6 cytokine and IL-8 chemokine compared to control cells, to inhibit VEGF, a proangiogenic factor, a biochemical proactive factor in destructive processes of OA, as well as the proven existence of the antioxidant activity of Alflutop. The data of numerous clinical studies (including the double blind placebo-controlled) show that it has an expressed analgesic effect, developing in the first weeks after administration in osteoarthritis patients, including with periarthrites, osteochondrosis, with back pain of different genesis, and the existence of the anti-inflammatory effect and a positive impact on the quality of life of osteoarthritis patients. At a high evidentiary level, the structural modifying effect of Alflutop and its safety is confirmed.

The main clinical manifestations of osteoarthritis (OA) are a painful articular syndrome of varying intensity accompanied by loss of functionality and impaired quality of life. The pathogenetic links of the degradation are related to violations of the hyaline cartilage structure. Collagen defects are practically not restored, worsening the dysfunction of joints. Alflutop is the cartilage protector, including chondroitin sulfate. In the literature its symptom - and the structure-modifying effect is shown. In the study we conducted in 60 patients the dynamics of painful articular syndrome, functional features and the quality of life of patients in case of complex treatment with alflutop were studied.

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 concomitant 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.

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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.

The paper presents the results of studying the impact of long-term treatment with theraflex (a 3-year follow-up) or alflutop (a 5-year follow-up) in patients with knee osteoarthosis. Both drugs have been shown to exert a positive effect on the symptoms of the disease. It has been concluded that theraflex affects more actively the pathogenic mechanisms in the progression of gonarthrosis.

Objective. To assess efficacy and safety of intramuscular (im) and paravertebral (pv) alflutop injections in pts with chronic vertebrogenous lumbar ischialgia. Material and methods. 83 pts with lumbar ischialgia syndrome (44 male, 39 female) aged 31 to 56 years (mean 43,1 ±5,2 years) were included. Disease duration varied from I to 7 years (mean 3,5± 1,9 years), duration of the present exacerbation - from 1 to 4 months (mean 2.4±0,8 months). Vertebroneurologic diagnosis was made according to H. Hall criteria. Pts were randomized into 4 groups. 32 pts of group Al received im, 23 pts of group A2 - pv alflutop injections. 14 pts of group Bl and 14 pts of group B2 received im and pv placebo injections respectively. Treatment results were scored by the doctor. Pts assessed spine pain changes on visual analog scale. Quantitative assessment of verbal syndrome was performed with Waddle scale. Results. Im alflutop injections provided good or fair effect in 61%, pv - in 69% of pts (significantly better than placebo). Effect was evident during the first 2 weeks of treatment and persisted for 3 months after its termination. The best results were achieved in pts with facet syndrome, the worst - in spinal stenosis. Drug tolerability was good in both modes of administration.

Objective. To assess alflutop clinical efficacy and safety during long-term course treatment of knee osteoarthritis. Methods. 51 pts with definite knee osteoarthritis of I-III stage according to Kellgren-Lawrence classification were included in an open controlled study. 20 pts received 6 intra-articular injections of alflutop 2 ml with subsequent intramuscular treatment during 3 months. Such courses were repeated 6 months apart for 2 years. 31 pts of control group received nonsteroidal anti-inflammatory drugs (NSAID) only. Pain on visual analog scale, Leken functional score, changes of NSAID treatment and radiological picture were used for assessment of efficacy. Clinical examination was performed before and after every treatment course and 3 months after the last course. Results. Every alflutop treatment course provided significant stepwise decrease of pain with improvement of mobility, reduction of NSAID requirement and absence of osteoarthritis radiological progression. Doctor and pts clinical efficacy and safety assessment coincided. Conclusion. Alflutop is an effective drug for knee osteoarthritis treatment. It has anti-inflammatory and probably chondroprotective activity with good safety.

Objective. To study efficacy and safety of different schemes of alflutop (AT) administration in pts with osteoarthritis (OA). Material and methods 45 pts (40 womene and 5 men) with knee or hip OA or nodular form of the disease were included. Mean age was 60,3± 10,0 years, mean disease duration - 8,0±6,0 years, mean duration of the last exacerbation - 5,6±5,4 months. Pts with 2 (27 pts) and 3(15 pts) X-ray OA stage and 2 functional class (30 pts) prevailed. Pts were devided into 3 comparable groups, 15 pts in each. Pts of the group 1 received AT I ml/day intramuscularly (im) during 3 weeks, group 2 pts received intra-articular (ia) injections of AT 2 ml twice a week for 3 weeks and then im for 20 days. In group 3 ia (6) and im (20) injections were performed^simultaneously. During 12 months of follow up every pt received 2 appropriate courses. Results. 41 pts completed the study. AT significantly decreased joint pain at rest and at movement measured visual analog scale and WOMAC index in all groups. It also improved functional activity of pts (according to WOMAC index). Improvement according to doctor assessment was achieved after the second course in 78% of pts in group I, in 92% in group 2 and in 86% in group 3. Sonography of knee joints showed significant decrease of synovial membrane thickness (as a sign of synovitis) as well as increase parts of intra-articular hyaline cartilage thickness in group 2 and 3 pts. There was no radiological progression year of follow up. Tolerability was good. The drug was stopped due to adverse events in only 3 pts (dermatitis at the site of injection-1, increase of joint pain after intra-articular injections- 2) . In 3 other pts side effects were mild, and treatmend was continued. Conclusion. Combined Im and AT administration provides anti-inflammatory, analgesic and possible chondroprotective effect in OA pts.

Summary Aljlutup is an effective and well tolerable drug which not only decreases pains and other clinical manifestations of secondary synovitis but also has positive effect on the structure of articular cartilage.

Objective: To analyze the effect of Alflutop on neuroinflammation in patients with chronic lower back pain (CBP)., Material and Methods: Forty-one patients with a verified CBP diagnosis were enrolled in the study. Alflutop was used for treating CBP, 1 ml once/day, for 20 days. Treatment efficacy was monitored using the Visual Analogue Scale (VAS), DN4 test; the Roland-Morris questionnaire; the index of pain activity in the lumbar spine; and the level of tumor necrosis factor-α (TNF-α) in blood plasma. There were three visits in total: screening (visit 0), treatment start (visit 1, 0-3 days after screening) and visit 2 (3 months later (±7 days) from the start of treatment)., Results: Before the start of therapy, in some patients (group 1, n =14 (34.1%) the TNF-α concentration in the blood plasma was below the detectable level (less than 4.0 pg/ml), while in group 2 ( n =27 (659%)), the expression of TNF-α in peripheral blood was observed at the level of 6.3 [4.9; 7.4] pg/ml. Patients in group 2 significantly ( p <0.05) differed from patients in group 1 by the greater number of CBP exacerbations over the last year as well as by the results of testing on DN4 (higher values) and SBI (greater discomfort). In group 2, a significant relationship was found between the TNF-α level in blood plasma and the number of exacerbations as well as between the TNF-α level and the number of DN4 points. At visit 2, patients in group 2 had a significant ( p <0.05) decrease in pain intensity according to VAS, an improvement in the quality of life according to the Roland-Morris questionnaire, a decrease in the severity of the neuropathic component of pain according to DN4 test as well as subjective condition improvement associated with the activity of pain in the lumbar spine. A significant relationship was found between the level of TNF-α and the number of DN4 points after treatment and the period of active observation., Conclusions: In the majority of CBP patients, the high relapse rate and neuropathic nature of pain may be associated with persistent neuroinflammation due to TNF-α synthesis. Alflutop inhibits the TNF-α expression substantially, which significantly correlates with a decrease in the neuropathic pain syndrome component according to the DN4 questionnaire. The use of Alflutop can be considered as an effective method of treating patients with CBP, which has an impact on the process of neuroinflammation as one of the leading causes of changes in the pain nature and its chronicity.

The back pain is one of the most common and socially significant neurological syndromes, leading to limited mobility and household independence of elderly patients. Specific «serious» causes of back pain account for 1-2% of all cases of back pain, approximately 10% of cases of pain correspond to radiculopathy, while the rest of the most common variants is related to nonspecific axial back pain. In the most cases of back pain, a clear connection between degenerative-dystrophic changes in the spine and the clinical manifestations and intensity of back pain is absent. On the other hand, dystrophic changes in the spine, which under certain conditions can be a source of chronic pain, cannot be completely ignored. Therefore, «osteochondrosis» is currently considered as a heterogeneous cascade process with the different course variations. In practice, it is not always possible to draw a line between nociceptive, neuropathic, nociplastic and psychogenic pain, more often in this case we can talk about a mixed nature of pain. Unreasonable neuroimaging with the identification of «accidental» findings can complicate the interpretation of the causes of pain, however, it is absolutely indicated to exclude serious specific diseases, spinal stenosis, when determining the indications for surgery. The presence of comorbid affective disorders, certain personality characteristics of patients contributes to the persistent nature of low back pain, therefore it is important to take these factors into account when diagnosing the causes and treatment of pain. Along with conventional anti-inflammatory drugs and other analgesics with a proven effect in the complex treatment of patients with degenerative-dystrophic changes in the spine with radicular and non-root pain syndromes, Symptomatic Slow - Acting Drugs in Osteoarthritis can be recommended.

Objective: Evaluation of Alfultop impact on nociceptive afferentation central mechanisms in patients with chronic lower back pain., Materials and Methods: The study involved 40 patients with CLBP. The therapy included Alflutop, 2 ml once a day for 10 days. Mean VAS-pain, LANSS, Roland-Morris questionnaire, Global Rating of Change Scale (GRC), pressure pain thresholds data were analyzed. Follow-up duration was 3 months., Results: Most of the patients were females (f:m=1.3:1); average age - 60.5 [54.2; 67.3] years with a mean disease duration of 14.3±4.2 mo. At visit 1, the VAS score was 63.2±9.4, LANSS 14.2±2.1 points, and the Roland-Morris questionnaire 9.9±3.5 points. There was a significant decrease in the pain threshold both in the zone of maximum pain, located in the lower back (3.97±0.9 kg/sm 2 ), and in suprasegmental area (5.22±1.7 kg/sm 2 ), and a pathological change in the temporal summation of pain (789.2±45.6 mm). After Alflutop therapy, significant changes in the parameters of the VAS, LANSS and Roland-Morris scores were recorded after 30 days of observation and maximum changes in 3 months. The pain threshold has significantly increased after 3 months of observation. The majority of patients rated the improvement from the therapy as «moderate» and «pronounced» (33/82.5%) according to the GRC scale. A significant relationship was established between the level of pain threshold and the intensity of pain on the VAS scale (R=0.714), its duration (R=0.799) and disability of the patients (R=0.706)., Conclusions: Central sensitization develops in patients with CLBP, which correlates with VAS score of pain intensity, its duration and the degree of disability. Alflutop significantly reduces the intensity of the pain syndrome, its neuropathic component, significantly increases the level of pain threshold and improves the disability of patients in 3 months after the start of treatment.

The concept of chronic nonspecific back pain (CNBP) as a pathology of the spine (osteochondrosis, spondylosis, intervertebral disc herniation, facet syndrome) is extremely outdated and has not justified itself, first of all, from the therapeutic view point. Numerous studies, including meta-analyzes and systematic reviews, have convincingly shown the ineffectiveness of the methods of CNBP treatment, aimed only at solving the problems of the spine itself and / or surrounding tissues. A substantial amount of special imaging studies have proven the dissociation between morphological vertebral changes and the clinical picture of pain. CNBP is the overall result of the interaction of numerous factors in the spine tissues (changes in the discs, joints, ligaments, fascia, muscles) and factors beyond the spine. The latter include, first of all, psychological and social factors, cognitive functions, the quality of night sleep, the level of physical activity, concomitant diseases (comorbidity). In each patient, the interaction of these factors determines the development of specific pathophysiological mechanisms of pain and, as a result, an individual clinical picture of pain (phenotype). Understanding these processes will allow for the reconsideration of the approach of searching for an anatomical pain source as the main pathogenetic factor; recognizing the multifocal generation of chronic pain as the result of a complex interaction of biological, psychological and social factors; the development of new principles and therapy algorithms. The authors propose to introduce into practice a multidomain screening approach for evaluating patients with CNBP, which would take into account the phenotype of pain, factors affecting its perception, and allow personalized treatment for each patient based on the biopsychosocial approach.

Aim: To evaluate the potential of local injection therapy with Alflutop in management of paraarticular tissue lesions (PTL)., Material and Methods: 44 patients with various localization of PTL were examined and exposed to treatment., Results: As a result of local therapy with Alflutop, the majority of patients with PTL experienced a decrease in pain syndrome and an increase in the functional capabilities. There was no negative dynamic of symptoms., Conclusion: Treatment with Alflutop was well tolerated by patients, easily applied, had a small number of side effects and was accompanied by a pronounced clinical effect.