[Efficacy and safety of undenatured type II collagen in patients with knee osteoarthritis: a multicenter, prospective, double-blind, placebo-controlled, randomized trial].

BACKGROUND: Non-pharmacological treatments based on collagen as a dietary supplement are emerging as a new area of interest to support preventive or therapeutic effects in patients with osteoarthritis (OA). AIM: In a multicenter, prospective, double-blind, placebo-controlled, randomized study, to evaluate the effectiveness and safety of the use of the Artneo complex containing undenatured chicken collagen type II in patients with OA of the knee joints. MATERIALS AND METHODS: The study enrolled 212 outpatients from 12 centers in the Russian Federation with knee OA, stages II and III according to the Kellgren-Lawrence classification. The participants included 171 women (80.7%) and 41 men (19.3%), with an average age of 60.2±9.0 years (range: 40 to 75 years). The study population was randomly allocated in equal proportions into two groups using an interactive web response system (IWRS). Group 1 (Artneo) consisted of 106 patients who took one capsule of the drug once daily for 180 days. Group 2 (Placebo) also had 106 patients, with the dosage form and regimen identical to Group 1. During the treatment period, the following outcomes were assessed: WOMAC index, KOOS, pain according to VAS, quality of life using the EQ-5D questionnaire, and the need for NSAIDs. All patients underwent a clinical blood test, general urine analysis, biochemical blood test, and ultrasound examination of the affected knee joint. RESULTS: In a prospective, double-blind, placebo-controlled, randomized study, it was demonstrated that the Artneo combination, containing undenatured chicken collagen type II, has a positive effect on all clinical manifestations of OA: it effectively reduces pain, stiffness, and improves the functional state of joints and quality of life. It has a good safety profile and is superior to placebo in all parameters studied. CONCLUSION: The results of the study confirm the good effectiveness and safety of the Artneo combination in patients with OA of the knee joints.

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.

[Comparative efficacy of a combination of undenatured type II collagen, Boswellic acids, methylsulfonylmethane, vitamins C and D3 and a combination of chondroitin sulfate and glucosamine hydrochloride in the treatment of primary osteoarthritis of the knee joint].

AIM: To evaluate the efficacy of Artneo (AN) in comparison with a combination of glucosamine hydrochloride and chondroitin sulfate (GC) in patients with osteoarthritis (OA) of the knee joint (KJ). MATERIALS AND METHODS: 70 patients with stages I-III of primary knee OA were randomized into 2 groups. Participants in the 1st (n=35) took AN 1 caps/day, in the 2nd (n=35) GC according to the standard regimen. After 7, 30, 90, 180 days, the Lequesne index (severity of OA), pain when moving according to VAS, WOMAC score were assessed, after 1, 3, 6 months - quality of life SF-36 and morning stiffness, after 6 months - MRI with T2 mapping, laboratory safety indicators. RESULTS: Over the course of 6 months of use, an improvement in the WOMAC index and a decrease in pain were observed without intergroup differences, and a greater decrease in stiffness in the AN group. After 3 months, the severity of OA decreased from moderate to mild in the AN group and was significantly lower compared to the GC group; quality of life (physical component of SF-36) was higher in the AN group. After 6 months, there was an improvement in cartilage ultrastructure (T2 relaxation time) in both groups and a more pronounced reduction of the synovitis area (MRI) in the AN group (2.95 and 1.37 times in the AN and GC group, respectively). There were no clinically significant adverse reactions observed in both groups. CONCLUSION: The use of AN in patients with stage I-III primary knee OA was not inferior in efficacy to the combination of GC. Further studies with greater statistical power (sample size) and follow-up period are warranted including in real clinical practice.

[Portable telemedical complex usage perspectives for medical care of elderly and senile patients with cerebrovascular pathology.]

The article discusses perspectives of medical care in elderly and senile patients with cerebrovascular pathology with portable telemedical complex use. Analysis of telemedical cooperation physician-consultant-patient and discussion of medical equipment criteria for telemedical complex selection and organizational together with legal issues of medical data transfer, storage and access were performed. The important clinical features of cerebrovascular pathology in elderly patients were presented, which determined necessity of highly qualified medical specialist involvement in management of such patients. The opportunities of portable medical complex usage were discussed.

[The efficacy and safety of eculizumab biosimilar in patients with paroxysmal nocturnal hemoglobinuria. Results of a phase III randomized open-label comparative clinical trial].

AIM: To establish the equivalent efficacy and comparable safety profile of biosimilar Acveris and referent eculizumab product Soliris used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH). MATERIALS AND METHODS: Were included in the phase III multicenter 28 PNH patients, open-label clinical trial. Participants were randomized (1:1) into 2 treatment groups: investigational product (Acveris, n=14) and referent product (Soliris, n=14). Patients received eculizumab as the intravenous infusion 600 mg once a week during the first 4 weeks, 900 mg at week 5 and then 900 mg every 14 days (2 days) up to week 27 of the study. The efficacy, pharmacokinetics, pharmacodynamics, safety and immunogenicity of the compared products were analyzed after the end of 27 weeks of the study. The primary efficacy endpoint was the area under the curve LDH concentrationtime (AUCLDH) throughout the study period weeks 527. RESULTS: The difference between the mean AUCLDH values between the Acveris and Soliris groups was 5380.0 [-38 773.87; 49 533.87] U/ldays. The 95% CI limits for the difference in mean AUCLDH values between the groups fit the preset 95% CI [-146 500.9146 500.9] U/ldays and establish the equivalent efficacy of the biosimilar and referent product according to the primary efficacy endpoint. The safety profile of both Acveris and Soliris was expected and comparable according to the proportion of patients with adverse events. The formation of binding antibodies to eculizumab was not detected in both the groups. CONCLUSION: The study established the equivalent efficacy of biosimilar product Acveris and referent eculizumab product with the evidence of effective suppression of intravascular hemolysis in PNH patients along with a comparable favorable safety profile.

[The efficacy of non-sreroidal anti-inflammatory drugs]. / Éffektivnost' nesteroidnykh protivovospalitel'nykh preparatov.

The paper presents current views on the efficacy of nonsteroidal anti-inflammatory drugs (NSAID). The authors analyze strengths and weaknesses of modern approaches and trends in the use of NSAID and highlight promising directions for clinical research of NSAIDs' efficacy.

Factors affecting the results of analgesic therapy. Results of the Russian multicentre study of NOTE (NSAID: Open-label Trial of Efficacy).

AIM: To identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. MATERIALS AND METHODS: An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). RESULTS: Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p<0.001). CONCLUSION: NSAIDs are the first-line medications for the pain treatment in LBP and OA. Aceclofenac is effective and safe in this conditions. When carrying out analgesic therapy should take into account factors that affect the effectiveness of treatment: old age, overweight, insufficient effect of NSAIDs in history, severe pain, signs of "inflammatory" pain, multiple sources of pain.

The Diagnostic Value of Alpha-1-Antitrypsin Phenotype in Patients with Granulomatosis with Polyangiitis.

The deficiency of alpha-1 protease inhibitor, or alpha-1-antitrypsin (A1AT), predisposes to chronic lung diseases and extrapulmonary pathology. Besides classical manifestations, such as pulmonary emphysema and liver disease, alpha-1-antitrypsin deficiency (A1ATD) is also known to be associated with granulomatosis with polyangiitis (GPA or Wegener's granulomatosis). The aim of our study was to evaluate the frequency of allelic isoforms of A1AT and their clinical significance among GPA patients. Detailed clinical information, including Birmingham Vasculitis Activity Score (BVAS), incidence of lung involvement, anti-proteinase 3 (PR3) antibodies concentrations, and other laboratory data were collected in 38 GPA patients. We also studied serum samples obtained from 46 healthy donors. In all collected samples A1AT phenotyping by isoelectrofocusing (IEF) and turbidimetric A1AT measurement were performed. Abnormal A1AT variants were found in 18.4% (7/38) of cases: 1 ZZ, 4 MZ, 2 MF, and only 1 MZ in control group (2%). The mean A1AT concentration in samples with atypical A1AT phenotypes was significantly lower (P = 0.0038) than in normal A1AT phenotype. We found that patients with abnormal A1AT phenotypes had significantly higher vasculitis activity (BVAS) as well as anti-PR3 antibodies concentration. We conclude that A1AT deficiency should be considered in all patients with GPA.

[Innovative Methods of Some Systemic Autoimmune Diseases Treatment].

In the present paper we consider the problem of innovative treatment of systemic autoiminune diseases for example, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). The use of biological therapy is suitable for severe rheumatoid arthritis and promotes remission in 25-30% of cases. Application biological therapy (as anti-B cell therapy) in cases of systemic lupus erythematosus severe forms can reduce the immuno activity level, and also leads to the regression of secondary vasculitis in lung tissue and renal parenchyma. The analysis of drugs and principles of treatment of rheumatoid arthritis and systemic lupus erythematosus was done. Particular attention is paid to the safety and efficacy of biological agents and synthetic base anti-inflammatory drugs.

Efficacy and safety of infliximab plus naproxen versus naproxen alone in patients with early, active axial spondyloarthritis: results from the double-blind, placebo-controlled INFAST study, Part 1.

OBJECTIVES: To assess whether combination therapy with infliximab (IFX) plus nonsteroidal anti-inflammatory drugs (NSAIDs) is superior to NSAID monotherapy for reaching Assessment of SpondyloArthritis international Society (ASAS) partial remission in patients with early, active axial spondyloarthritis (SpA) who were naïve to NSAIDs or received a submaximal dose of NSAIDs. METHODS: Patients were randomised (2 : 1 ratio) to receive naproxen (NPX) 1000 mg daily plus either IFX 5 mg/kg or placebo (PBO) at weeks 0, 2, 6, 12, 18 and 24. The primary efficacy measure was the percentage of patients who met ASAS partial remission criteria at week 28. Several other measures of disease activity, clinical symptoms and patient-rated outcomes were evaluated. Treatment group differences were analysed with Fisher exact tests or analysis of covariance. RESULTS: A greater percentage of patients achieved ASAS partial remission in the IFX+NPX group (61.9%; 65/105) than in the PBO+NPX group (35.3%; 18/51) at week 28 (p=0.002) and at all other visits (p<0.05, all comparisons). Results of most other disease activity and patient-reported endpoints (including Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, multiple quality of life measures and pain measures) showed greater improvement in the IFX+NPX group than the PBO+NPX group, with several measures demonstrating early and consistent improvement over 28 weeks of treatment. CONCLUSIONS: Patients with early, active axial SpA who received IFX+NPX combination treatment were twice as likely to achieve clinical remission as patients who received NPX alone. NPX alone led to clinical remission in a third of patients.

Maintenance of biologic-free remission with naproxen or no treatment in patients with early, active axial spondyloarthritis: results from a 6-month, randomised, open-label follow-up study, INFAST Part 2.

OBJECTIVE: To investigate whether biologic-free remission can be achieved in patients with early, active axial spondyloarthritis (SpA) who were in partial remission after 28 weeks of infliximab (IFX)+naproxen (NPX) or placebo (PBO)+NPX treatment and whether treatment with NPX was superior to no treatment to maintain disease control. METHOD: Infliximab as First-Line Therapy in Patients with Early Active Axial Spondyloarthritis Trial (INFAST) Part 1 was a double-blind, randomised, controlled trial in biologic-naïve patients with early, active, moderate-to-severe axial SpA treated with either IFX 5 mg/kg+NPX 1000 mg/d or PBO+NPX 1000 mg/d for 28 weeks. Patients achieving Assessment of SpondyloArthritis international Society (ASAS) partial remission at week 28 continued to Part 2 and were randomised (1:1) to NPX or no treatment until week 52. Treatment group differences in ASAS partial remission and other efficacy variables were assessed through week 52 with Fisher exact tests. RESULTS: At week 52, similar percentages of patients in the NPX group (47.5%, 19/40) and the no-treatment group (40.0%, 16/40) maintained partial remission, p=0.65. Median duration of partial remission was 23 weeks in the NPX group and 12.6 weeks in the no-treatment group (p=0.38). Mean Bath Ankylosing Spondylitis Disease Activity Index scores were low at week 28, the start of follow-up treatment (NPX, 0.7; no treatment, 0.6), and remained low at week 52 (NPX, 1.2; no treatment, 1.7). CONCLUSIONS: In axial SpA patients who reached partial remission after treatment with either IFX+NPX or NPX alone, disease activity remained low, and about half of patients remained in remission during 6 months in which NPX was continued or all treatments were stopped.

[The quality of life in patients with rheumatoid arthritis treated with rituximab].

The aim of the work was to assess the quality of life in patients with rheumatoid arthritis treated with rituximab in combination with methotrexate or methotrexate monotherapy. The statistically significant improvement of quality of life in both groups 12 months after onset of the treatment was roughly identical. Rutiximab was prescribed after ineffective treatment with TNF-α inhibitors.

[Sergey Petrovich Botkin is the founder of Russian therapeutic school].

The paper gives basic facts from the life and work of Sergey Petrovich Botkin, one of the coryphaei of Russian medicine, who played a prominent role in the formation and development of Russian clinical medicine and became the founder of the most well-known therapeutic school in Russia. S.P. Botkin's greatest merit is emphasized to be his neurogenic theory of medicine, which has played a great role in the understanding of physiological and pathological processes in the entire organism.

[The efficiency and safety of adalimumab treatment in patients with active rheumatoid arthritis unresponsive to standard therapy: Russian national study results].

AIM: To confirm the efficacy and safety of adalimumab (ADA) added to the standard antirheumatic therapy performed in patients with rheumatoid arthritis (RA) of moderate and high activities. SUBJECTS AND METHODS: The open-labeled multicenter study enrolled 100 adult patients (11 men, 89 women; mean age 50.9 +/- 11.1 years) with active RA according to the ACR criteria (1987) despite their treatment with disease-modifying antirheumatic drugs, the average number of which in the history was 2.1 per man. At baseline, DAS28 CRP was as many as 6.2 +/- 0.84 scores; C-reactive protein (CRP) was 37.1 +/- 34.7 mg/l. In accordance with the indications officially registered in the European Union and the Russian Federation, ADA was given in a dose of 40 mg 2 weeks. Before administration of the drug, every patient underwent screening examination for tuberculosis, which used a tuberculin test and chest X-ray. The screening covered a period of the treatment up to 24 weeks and its subsequent period within 70 days after administration of the last dose of ADA in order to study its safety. RESULTS: DAS28-CRP scores decreased from 6.14 +/- 0.86 (at baseline) to 3.39 +/- 1.1 (by the end of the study). At 12 weeks, 22% of the patients achieved a low RA activity (DAS28-CRP < or = 3.2 scores); 14% achieved clinical remission (DAS28-CRP < or = 2.6 scores); at 24 weeks, these were 37 and 25% of the patients, respectively. There were differences in effectiveness in terms of the baseline disease activity. At 24 weeks, ACR20, ACR50, and ACR 70 responses were achieved in 88, 67, and 26% of the patients, respectively. The HAQ functional index reduced from 1.9 +/- 0.6 (at baseline) to 1.081 +/- 0.64 (at 12 weeks) and 1.04 +/- 0.68 (at 24 weeks) scores. Twenty-four patients were recorded as having 40 adverse reactions (AR), including only one severe AR (septic arthritis). There were no cases of tuberculosis. CONCLUSION: The Russian multicenter study demonstrated the high clinical efficacy of ADA in patients with the moderate and high activity of RA unresponsive to standard therapy, as well as its satisfactory safety.

[Clinical and morphological features of infectious endocarditis in HIV-infected intravenous drug abusers].

The aim of this work was to study the clinical course and morphogenesis of infectious endocarditis in HIV-infected intravenous drug abusers. In this patients, endocarditis was an acute disease with high frequency of thromboembolic complications and ill-defined exudative component of the inflammatory reaction. Autopsies dated to 1993-2008 showed that neither the presence of morphological signs of early HIV infection nor chronic hepatitis C with minimal or moderate inflammation has an appreciable effect on the intrahospital mortality rate in these patients.

[Systemic enzymotherapy in the combined treatment of infectious endocarditis in drug addicts].

The aim of this study was to elucidate effects of systemic enzymotherapy on the clinical course of infectious endocarditis and the frequency of thromboembolic complications in drug addicts compared with controls. Another objective was to develop an optimal regime of enzymotherapy depending on the severity of the disease. Inclusion of wobenzyme in the combined treatment of infectious endocarditis permitted to accelerate the achievement of clinical improvement, normalize blood rheologic characteristics, reduce severity of intoxication and systemic inflammation, decrease the frequency of septic thromboembolia of the pulmonary artery.

[Administration of monoclonal antibodies to B-lymphocytes (rituximab) in rheumatoid arthritis in Russia].

AIM: To assess efficacy and tolerance to anti-B-cell drug rituximab in therapy of rheumatoid arthritis (RA) by the data of RF register of this drug. MATERIAL AND METHODS: Rituximab was studied in 42 patients with high RA activity. 37 patients received rituximab according to a conventional scheme: 2 intravenous 1000 mg infusions with a 2-week interval. The rest patients received 2 intravenous 500 mg infusions. The response was evaluated by DAS28 index. RESULTS: Rituximab administration resulted in almost complete elimination of B-cells from peripheral blood. This produced a significant positive effect manifesting with reduction in the number of inflamed and painful joints. This trend was evident to observation week 8 reaching maximum to week 24. Clinical response correlated with decline of inflammation as shown by ESR and CRP. According to DAS28 index, good and satisfactory results were registered in 8 weeks in 62% patients, in 16 weeks--in 86%, in 24 weeks--in 100%. Rituximab tolerance was good. CONCLUSION: Effective treatment with rituximab for rheumatoid arthritis opened a new perspective in antirheumatic biological therapy and demonstrated an important role of B-cells in the disease development. This drug is recommended for wide use in the treatment of severe rheumatoid arthritis resistant to prior therapy including TNF-alpha blockers.

[The results of conservative therapy and the analysis of survival rate in drug addicted patients with infectious endocarditis].

110 drug addicted patients with infectious endocarditis (IE), 67 males and 43 females with average age 24 +/- 3.2 years were examined. Positive results of conservative therapy were in 69.2% patients with isolated lesion of tricuspid valve. Hospital lethality in the group of patients was 35.5% (39 cases). The analysis of survival rate of IE patients with the use of Cox's regression model made possible to establish that main predictors of lethal outcome in the group of patients were dimensions of microbe vegetations on tricuspid valve more than 2 cm, development of acute left ventricle failure, DIC-syndrome, and high degree tricuspid valve failure. Presence of HIV in early stage and C hepatitis without clinical laboratory activity did not have significant influence on IE outcome in this group of patients.