EFFECT OF METOPROLOL ON COGNITIVE FUNCTION IN HYPERTENSIVE PATIENTS OF YOUNG TO MIDDLE AGE

Aim. To evaluate the effect of metoprolol tartrate on blood pressure (BP) and cognitive function in young to middle aged patients with essential hypertension (HT).Material and methods. 40 men (age of 49,0±1,9 y.o.) with HT of I-II stage not taking antihypertensive medication regularly were enrolled into the study. All patients were given metoprolol tartrate (start dose 50-100 mg/d). Variables of 24-h BP monitoring and clinic BP, left ventricular mass index (measured by echocardiography) and characteristics of cognitive function (memory, attention, thinking and neurodynamic) were assessed at the start, after 1 and 6 months of therapy.Results. Good and satisfactory antihypertensive effect was achieved in 75% of hypertensive patients with metoprolol (186,6±13,4mg/d) monotherapy. Metoprolol significantly decreased maximum day-time systolic and diastolic BP, maximum night-time diastolic BP, mean day-time systolic and night-time diastolic BP, time-index, load-index and variability-index for night-time diastolic BP, day-time and night-time pulse BP. Left ventricular mass index reduced significantly (p<0,0001). After 6 months of therapy significant improvement of memory, attention, thinking and neurodynamic was observedConclusion. Metoprolol had beneficial effect on cognitive function in hypertensive patients, which demonstrate its cerebroprotective properties in addition to antihypertensive action. Metoprolol can reduce the risk of dementia in young to middle aged patients with HT

Difficulties in diagnosing atypical hemolytic uremic syndrome

The paper presents the case of clinical observation of a patient with atypical hemolytic-uremic syndrome (aHUS). aHUS is a disease characterized by an unfavorable prognosis (severe or catastrophic course with rapid development of terminal renal or multi-organ failure). The aim of the study is to evaluate the approaches to differential diagnosis of aHUS in clinical practice.Material and methods. The study was conducted on the basis of the Nephrology Department of Kemerovo Regional Clinical Hospital n.a. S.V Belyaev. The clinical observation of patient D., aged 26 years old, is discussed.Results and discussion. Diagnosing aHUS requires: 1) diagnosing thrombotic microangiopathy (TMA: thrombocytopenia or decrease in platelet count by more than 25 % of original, visceral damage (kidneys, CNS, gastrointestinal tract, heart, lungs)); 2) ruling out HUS associated with Shiga toxin-producing Escherichia coli (STEC-HUS; negative for Shiga-toxin in blood and stool), thrombotic thrombocytopenic purpura (TTP), systemic connective tissue disease, catastrophic antiphospholipid syndrome, HIV infection; 3) assessing the activity of ADAMTS13 (decrease confirms the aHUS diagnosis); 4) proving normal content of complement components C3 and C4 as an additional argument in favor of aHUS diagnosis. At the first stage, the patient was diagnosed with TMA (platelet content 37 x 109/l, hemoglobin content 59 g/l), LDH up to 824 E/l), liver damage (AST, ALT and LDH activity 55, 60 and 824 U/l, respectively), kidney damage (acute renal damage), lungs, heart, and brain damage. At the second stage the following diagnoses were ruled out: STEC-HUS (Shiga toxin in blood and stool was not detected), TTP (ADAMTS13 activity level was 66 %, whereas reference values are 93-113 %, in TTP - below 5-10 %); systemic connective tissue diseases catastrophic antiphospholipid syndrome, HIV infection sepsis. Normal values of C3 (0.9 g/l) and C4 (0.23 g/l) complement components did not rule out the diagnosis of aHUS

Эффективность и безопасность левилимаба в сочетании с метотрексатом при лечении пациентов с активным ревматоидным артритом, устойчивым к монотерапии метотрексатом (двойное слепое рандомизированное плацебо-контролируемое исследование III фазы, SOLAR)

Levilimab is anti-interleukin-6 receptor (IL6R) monoclonal antibody. The article presents data obtained during 24 weeks of the SOLAR phase III study.Objective: to confirm efficacy and safety of levilimab in combination with methotrexate (MTX) in patients with methotrexate resistant active rheumatoid arthritis (RA).Patients and methods. 154 adult patients, aged ≥18 years with the diagnosis of RA (ACR/EULAR 2010) and confirmed disease activity at screening despite treatment with MTX for at least 12 weeks (in a stable dose 15-25 mg/week). Patients were randomized 2:1 in levilimab (162 mg once a week, subcutaneously) + MTX (n=102) or placebo + MTX (n=52) group.The hypothesis of superiority of levilimab over placebo was tested for two co-primary efficacy endpoints: proportion of subjects who achieved ACR20 at week 12 and proportion of subjects who achieved low disease activity (LDA) of RA (DAS28-CRP <3.2) at week 24. Safety was assessed through monitoring of adverse events (AEs).Results and discussion. Seventy (68.6%) subjects who received levilimab and 20 (38.5%) who received placebo achieved ACR20 response at week 12. Fifty three (52%) subjects who received levilimab and 3 (5,8%) subjects who received placebo achieved LDA at week 24. The most common adverse events (reported in ≥5% of subjects) in levilimab and placebo arms, respectively were (by decreasing frequency): blood c holesterol increase (24% vs 12%), alanine aminotransferase elevation (11% vs 8%), lymphocyte count decrease (9% vs 8%), blood total bilirubin increase (11% vs 0%), blood triglycerides increase (10% vs 2%), aspartate aminotransferase elevation (7% vs 4%), positive interferon-gamma release assay (IGRA) with M.tuberculosis antigen blood test (5% vs 6%), absolute neutrophil count decrease (8% vs 0%). No deaths were occurred.Conclusion. The study confirmed superior efficacy of levilimab + MTX over placebo + MTX in subjects with MTX resistant active RA. Levilimab showed favorable safety profile and low immunogenicity. No new important safety risks were detected.Левилимаб – моноклональное антитело к рецептору интерлейкина 6. В статье приведены данные, полученные в ходе 24 нед исследования III фазы SOLAR.Цель исследования – подтвердить эффективность и безопасность левилимаба в комбинации с метотрексатом (МТ) у пациентов с активным ревматоидным артритом (РА), устойчивым к монотерапии МТ.Пациенты и методы. Рандомизировано 154 пациента в возрасте 18 лет и старше с установленным диагнозом РА (критерии ACR/EULAR, 2010) и подтвержденной активностью заболевания, несмотря на терапию МТ (в стабильной дозе 15–25 мг/нед) в течение ≥12 нед. Рандомизация проводилась в соотношении 2:1 в группу левилимаба (162 мг, 1 раз в неделю, подкожно) в комбинации с МТ (n=102) или плацебо в комбинации с МТ (n=52).Превосходство левилимаба над плацебо было оценено по двум ко-первичным конечным точкам: доля пациентов, достигших 20% улучшения в течении РА в соответствии с ACR20 на 12-й неделе исследования; доля пациентов с низкой активностью РА (DAS28-СРБ <3,2) на 24-й неделе. Безопасность лечения левилимабом в сочетании с МТ оценивалась на основании мониторинга нежелательных явлений (НЯ).Результаты и обсуждение. На 12-й неделе терапии ACR20 достигли 70 (68,6%) и 20 (38,5%) пациентов группы левилимаба и группы плацебо соответственно. Низкая активность РА на 24-й неделе исследования выявлена у 53 (52%) пациентов, получавших левилимаб в сочетании с МТ, и у 3 (5,8%) пациентов группы плацебо. Среди наиболее частых (развившихся у ≥5% пациентов) НЯ в группах левилимаба и плацебо соответственно были зарегистрированы (в порядке убывания частоты) следующие отклонения в показателях крови: повышение уровня холестерина (24 и 12%), повышение активности аланинаминотрансферазы (11 и 8%), снижение числа лимфоцитов (9 и 8%), повышение уровня общего билирубина (11 и 0%), повышение уровня триглицеридов (10 и 2%), повышение активности аспартатаминотрансферазы (7 и 4%), положительный тест высвобождения интерферона гамма с антигеном M. tuberculosis (5 и 6%) и снижение абсолютного числа нейтрофилов (8 и 0%). Летальных исходов не было.Заключение. Результаты исследования подтвердили, что у пациентов с РА, устойчивых к монотерапии МТ, левилимаб в комбинации с МТ превосходит по эффективности плацебо с МТ. Левилимаб продемонстрировал благоприятный профиль безопасности и низкую иммуногенность. Не выявлено новых важных рисков, связанных с безопасностью

SPECIAL PROPERTIES OF THE LEFT VENTRICLE MYOCARDUM REMODELING IN ATHLETES WITH ARTERIAL HYPERTENSION

Aim. To assess the specifics of myocardium remodeling in sportsmen-weightlifters according to presence of arterial hypertension (AH).Material and methods. Totally 80 sportsmen-weightlifters were included at the age of 21,0 (18,5-25,0) years. Group of AH consisted of 42 (52,5%) men, and the group without AH — 38(47,5%). Investigation consisted in office BP measurement, ambulatory BP monitoring (ABPM), echocardiography (EchoCG). Results. In the group with AH index of left ventricle myocardial mass (ILVMM), left atrium sizes (LA), end-diastolic size (EDS), thickness of interventricle septum (IVS) and posterior wall of the left ventricle (PWLV) were significantly higher than in the group with normal BP. Left ventricle hypertrophy (LVH) (ILVMM >115 g/m2) was found in 8 (19,0%) of athletes with AH and in 5 (13,1 %) — without AH. By the results of regression and correlational analysis it was found that thickness of the left ventricle wall, ILVMM, LA size are closely related to mean values of SBP and DBP during the 24-hour period, including daytime and nocturnal values and pulse wave value. In weightlifters with AH we found statistically significant positive link of LA size and pulse pressure (r=0,47; p=0,0001). Diastolic dysfunction of the left ventricle(DDLV) was found in 12 (15%) of athletes, all of them had AH. Among sportsmen with the signs of DDLV normal geometrical properties of LV were found in 5 (41,6%), concentric remodeling in 1 (8,3%), concentric hypertrophy in 3 (25%) and eccentric hypertrophy in 3 (25%) of weightlifters.Conclusion. Pathological types of LV remodeling (concentric and eccentric hypertrophy) are significantly more prevalent in sportsmen with AH. AH predefines development of DDLV in weightlifters. In sportsmen without AH there is no diastolic dysfunction either with or without LVH

Neurodynamics in young and middle-aged patients with arterial hypertension

Aim. To evaluate neurodynamics parameters in young and middle-aged patients with arterial hypertension (AH).Material and methods. In total, 41 men with AH (main group), aged 38-59 years, were examined. The control group included 15 healthy men (mean age 42,4+1,5 years). Interviewing, physical examination, and 24-hour blood pressure monitoring (BPM) were performed. Cognitive function was assessed with psycho-physiological program complex " Status PF", including neurodynamics tests (time of simple and complex visual-motor reactions - SVMR, CVMR).Results. The results obtained verified cognitive dysfunction (CD) presence in young and middle-aged AH patients. At the same time, the interrelation between AH stage, AH duration and cognitive dysfunction type was U-shaped. The maximal CD was observed in individuals with AH duration <1 year or >10 years. Optimal cognitive function, possibly due to adaptation mechanisms, was detected in patients with AH duration of 5-10 years or in those aged 40-50 years. Inadequate BP decrease during nighttime was also associated with CD.Conclusion. CD in AH was observed not only in elderly patients, but also in young and middle-aged persons with early AH stages. The changes in latent time of psycho-motor reactions could be regarded as the first manifestation of neurodynamics disturbances

CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objective: to detect previously undiagnosed arterial hypertension in patients with chronic obstructive pulmonary disease (COPD) as a risk factor for cardiovascular mortality.Materials and methods. 43 patients with stage I–II of COPD and the absence of clinical signs of cardiovascular diseases were examined. Spirometry, body plethysmography and diffusing lung capacity (DLCO) were included in the respiratory system assessment. The cardiovascular system was assessed with echocardiography and ambulatory blood pressure monitoring (ABPM).Results. Despite the absence of obvious signs of cardiovascular lesions (an increase of office blood pressure, intracardiac hemodynamic changes), the following cardiovascular risk factors were identified: age (58.2 ± 2.0 years), male gender, smoking, hypercholesterolemia and dyslipidemia (total cholesterol 5.9 ± 0.9 mmol / l, low density lipoproteins 3.8 ± 0.5 mmol / l, triglycerides 1.8 ± 0.2 mmol / l). Correlation analysis has revealed the relation between several respiratory parameters and the severity of dyspnea and quality of life in patients with COPD, as well as its relation with lipid levels.Conclusion. The patients with COPD have a large number of risk factors for CVD. According to ABPM data, arterial hypertension was verified in 18 (41.9 %) of 43 patients with COPD at normal level of office blood pressure; moreover, 51.2 % of patients demonstrated low reduction of blood pressure during the night-time that nowadays, is considered to be a predictor of cardiovascular disease and sudden death

CARDIOVASCULAR RISK FACTORS IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Objective: to detect previously undiagnosed arterial hypertension in patients with chronic obstructive pulmonary disease (COPD) as a risk factor for cardiovascular mortality.Materials and methods. 43 patients with stage I–II of COPD and the absence of clinical signs of cardiovascular diseases were examined. Spirometry, body plethysmography and diffusing lung capacity (DLCO) were included in the respiratory system assessment. The cardiovascular system was assessed with echocardiography and ambulatory blood pressure monitoring (ABPM).Results. Despite the absence of obvious signs of cardiovascular lesions (an increase of office blood pressure, intracardiac hemodynamic changes), the following cardiovascular risk factors were identified: age (58.2 ± 2.0 years), male gender, smoking, hypercholesterolemia and dyslipidemia (total cholesterol 5.9 ± 0.9 mmol / l, low density lipoproteins 3.8 ± 0.5 mmol / l, triglycerides 1.8 ± 0.2 mmol / l). Correlation analysis has revealed the relation between several respiratory parameters and the severity of dyspnea and quality of life in patients with COPD, as well as its relation with lipid levels.Conclusion. The patients with COPD have a large number of risk factors for CVD. According to ABPM data, arterial hypertension was verified in 18 (41.9 %) of 43 patients with COPD at normal level of office blood pressure; moreover, 51.2 % of patients demonstrated low reduction of blood pressure during the night-time that nowadays, is considered to be a predictor of cardiovascular disease and sudden death.</p

Efficacy and safety of sarilumab in combination with methotrexate in patients with active rheumatoid arthritis and inadequate effect of methotrexate monotherapy (results of phase III MOBILITY study)

Objective: to study the efficacy and safety of rheumatoid arthritis (RA) treatment with monoclonal antibodies to interleukin 6 receptors (IL6R) – sarilumab (SAR) in combination with methotrexate (MT).Subjects and methods. The study included adult patients with moderate or severe RA and inadequate effect of MT monotherapy. Patients were randomized in a 1:1:1 ratio to subgroups receiving SAR (at doses of 150 or 200 mg) or placebo (PL) every 2 weeks in combination with a weekly intake of MT for 52 weeks. The primary endpoints of the study included the achievement of ACR20 after 24 weeks, the change of HAQ-DI after 16 weeks and assessment of radiological progression of joint destruction (modified total Sharp score mTSS) after 52 weeks.Results and discussion. In general, the initial characteristics of patients were similar in all groups. A statistically significant improvement of all three primary endpoints was found in the groups of patients treated with SAR 150 and 200 mg compared to the group of PL. ACR20 response after 24 weeks was achieved in 53.6% (p&lt;0.0005), 65.9 and 19.6% of patients respectively (p&lt;0.0001), the average change in HAQ-DI after 16 weeks was 20.53; 20.55 and 20.29 respectively (p&lt;0.0001); the average change in mTSS after 52 weeks was 0.49; 0.11 and 2.30, respectively (p&lt;0.0001).Conclusion. Both doses of SAR (150 and 200 mg every 2 weeks) in combination with MT demonstrated sustained clinical efficacy in patients with RA, which was confirmed by a significant improvement in symptomatic, functional and radiographic outcomes. SAR therapy was generally well tolerated. The adverse events observed in this study were consistent with the effects of the IL6 blockade

Efficacy and safety of a new original interleukin 17A inhibitor in the treatment of patients with active ankylosing spondylitis: results of a basic (BCD-085-3/AILAS) and extended (BCD-085-3ext/AILAS-II) phase II clinical trial

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

THE EFFICACY AND SAFETY OF RITUXIMAB BIOSIMILAR (ACELLBIA®) IN RHEUMATOID ARTHRITIS AS THE FIRST BIOLOGICAL AGENT: RESULTS OF PHASE III (ALTERRA) CLINICAL TRIAL

The Russian biotechnological company «BIOCAD» has designed a chimeric monoclonal antibody against CD20 (BCD-020, Acellbia®) that is a biosimilar of rituximab (RTM; MabThera®, F. Hoffmann-La Roche Ltd., Switzerland). In recent years, there has been evidence that RTM can be used at lower doses than those given in the standard recommendations and instructions for the use of this drug. This serves as the basis for the BCD-020-4/ALTERRA (ALTErnative Rituximab regimen in Rheumatoid Arthritis) trial, the objective of which was to investigate the efficiency and safety of using Acellbia® (at a dose of 600 mg twice at a 2-week interval) as the first biological agent (BA) for methotrexate (MTX)-resistant active rheumatoid arthritis (RA). The investigation enrolled 159 patients aged 18 to 80 years with active RA. After 24 weeks 65.7 and 29.4% of patients achieved 20% improvement by the American College of Rheumatology (ACR) criteria in the Acellbia® + MTX and placebo (PL) + MTX groups, respectively (p&lt;0.0001). The differences in the ACR20 response rate in the two groups were 36.3% (95% CI, 19.27–53.28%). There were significant differences between the groups in the ACR50 response rates: 28.4% and 5.9% (p=0.001) and in the ACR70 ones: 12.8% and only 2.0%, respectively (p=0.036). Analysis of all recorded adverse events (AE) frequency showed no significant differences between the patients in the study and control groups and demonstrates its equivalence with that of RTM (MabThera®); all the AE were expectable. It is noted that antibodies to RTM with binding and neutralizing activities had no impact on the efficiency and safety of therapy