Proteolytic enzymes have a variety of pharmacological effects, which determines their important role and place in clinical medicine. The aim of this study was to confirm the lymphostimulating effect of terrilytin, an integral part of the drug terridecase, and to study its effect on the pharmacokinetic parameters of cefotaxime. Materials and methods of research. Assessment of the rate of lymphatic drainage in the mesentery of mice by the time of removal of lymphotropic dye from it; determination of the concentration of the antibiotic cephalosporin antibiotic of the third generation cefotaxime in rabbit blood plasma during the day, blood plasma, intestinal tissues and liver of white mongrel mice after 1.5 and 24 hours of experiment by high-performance liquid chromatography. Results. It has been confirmed that terrilytin has a lymphostimulating effect. It has been established that this proteolytic enzyme has the properties of an endolymphatic conductor. Its preliminary administration increases the concentration of cefotaxime in the blood plasma of rabbits and mice compared with monovision of the antibiotic at all time points of the study, up to a day, and increases its content in the intestinal tissue of mice, both 1.5 hours and 24 hours after injection of drugs. Terrilytin does not affect the level of cefotaxime in the liver tissue of mice, but reduces the ratio of its concentrations "liver tissue/blood", which indirectly indicates a decrease in liver extraction of the antibiotic. Conclusion. Terrilytin in clinical practice was used topically (externally or electrophoretically), whereas our studies were conducted against the background of its parenteral administration. This obstacle can be overcome by using a polyglucine–modified form of terrilytin – terridecase, which is allowed for parenteral administration. In this regard, it is advisable to continue studying the combined drug terridecase in order to identify its ability to direct water-soluble antibiotics into the lymphatic system.

Drug-drug interactions (DDIs) are a major cause of hospital admissions, accounting for 16.6% of ADRs and about 1% of all hospital admissions. Polypharmacy is on the rise, with a Swedish population-based study of people aged ;;;75 years showing that the prevalence of polypharmacy increased from 27% in 1988 to 54% in 2001 and to 65% in 2006. The aim of the study was to analyze the databases on DDI and to assess the possibility of their use in managing the risks of pharmacotherapy in the Russian Federation and the EAEU. Results. The main DDI databases are characterized. The degree of inconsistency in data on the number of DDI, severity and clinical recommendations was determined. The basic requirements for the completeness of information in databases are formulated. The necessity to harmonize approaches to providing information about DDI, as well as the need to create local databases for medical organizations were revealed. A computer program has been created to minimize the risks of DDI in clinical practice, for expert and scientific purposes. Conclusions. Databases and programs for DDI have different goals, a different set of data on DDI with varying degrees of evidence, differences in assessment of severity, likelihood of occurrence, clinical recommendations for treatment and correction of DDI. The variability of information is due to the lack of a unified system for assessing the severity and likelihood of potential negative consequences of DDI; different purposes for creation; difference in budgets at creation. This situation leads to warning redundancy and physician fatigue from insignificant or unproven DDIs. Based on the identified requirements for local databases, a computer program for modeling rational pharmacotherapy for lower respiratory tract infections was created and received a certificate of state registration.

Aim. To evaluate the dapagliflozin as part of various treatment regimens in patients with heart failure (HF) with reduced ejection fraction (HFrEF) ≤40% receiving medications within federal preferential drug program to achieve the "Reduction of cardiovascular mortality" of the State Program "HealthCare Development". To estimate the costs of reducing the cardiovascular mortality rate by 1 death per 100 thousand of population and achieving 1 percentage point of the target indicator "Reduction of cardiovascular mortality".Material and methods. The target patient population was Russian patients aged over 18 years diagnosed with NYHA class II-IV HFrEF (≤40%), included in the federal preferential drug program. We used model developed based on the DAPA-HF study results. We assessed the costs of drugs, the number of lives saved, the impact of therapy on achievement of the target indicator "Reduction of cardiovascular mortality" and other indicators in the Russian Federation (RF) as a whole and in each subject of the Russian Federation while using dapagliflozin as part of various treatment regimens for HFrEF including angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARB) or angiotensin receptor-neprilysin inhibitor (ARNi), beta blockers, diuretics, mineralocorticoid antagonists, cardiac glycosides.Results. In 2024, the treatment cost of 181351 patients with HFrEF included in the federal preferential drug program with dapagliflozin in combination with standard therapy (ST) will be RUB9265,4 million; in combination with ST without ARNi (ST including ACEi/ARB) — RUB8161,7 million; in combination with ST including ARNi — RUB17837,3 million. The additional number of lives saved when using dapagliflozin in combination with standard therapy was 2394, in combination with standard therapy without ARNi — 2340, in combination with standard therapy, including ARNi — 2913. Costs of therapy per patient per year when using dapagliflozin in combination with standard therapy amounted to RUB51090,90; in combination with standard therapy without ARNI — RUB45004,72; in combination with standard therapy, including ARNI — RUB98358,00. In 2024, the percentage (%) of achievement of the federal target for dapagliflozin in combination with ST is 11,22%, while in combination with standard therapy without ARNi (ST including ACEi/ARB) — 10,96%, in combination with ST including ARNi — 13,65%. Achievement of a 1% target reduction in cardiovascular mortality in 2024 reqiored RUB828,1 million for dapagliflozin in combination with ST, while in combination with ST without ARNI (ST including ACEi/ARB) — RUB748,2 million, in combination with ST including ARNi — RUB1293,3 million.Conclusion. Among the 3 options considered for adding dapagliflozin to ST (ARNi or ACEi/ARB, including ACEi/ARB, including ARNi), ST without ARNI (ST including ACEi/ARB) has the lowest cost required to achieve a 1% target reduction in cardiovascular mortality. At the same time, the standard therapy with ARNI has the highest cost required to achieve a 1% target reduction in cardiovascular mortality, which indicates its least cost-effectiveness.

OBJECTIVE: Clinical and economic evaluation of using the dapagliflozin in addition to standard therapy for patients with CHF (Chronic Heart Failure) and concomitant type 2 DM (Diabetes mellitus).MATERIALS AND METHODS: All adult Russian patients with confirmed diagnosis of CVD and concomitant type 2 DM were considered as the target population. We evaluated the use of dapagliflozin in addition to standard therapy in comorbid patients with CHF and DM type 2 on the indicators of CC death, death from any cause of hospitalization due to CHF, emergency treatment due to CHF, as well as calculated the cost per life year saved and quality-adjusted life year (QALY) saved both when using standard therapy alone and in combination with dapagliflozin.RESULTS: The use of dapagliflozin in addition to standard therapy for the treatment of comorbid patients with CHF and DM 2 per cohort of 1,000 people will prevent an additional 1,3 and 10 years:CHD-related hospitalizations: 40, 99, 195, respectively;Emergency admissions due to CVD: 15, 38, 73 respectively;CC deaths: 9, 19, 25 respectively;Deaths from any cause: 10, 21, 19At the same time, the costs per one year of quality-adjusted life saved were 1,923,509 rubles during the first year, 1,102,680 rubles during the first 3 years, and 560,841 rubles for 10 years, which did not exceed the calculated value of the willingness-to-pay threshold — 3.14 million rubles, and allowed us to conclude that dapagliflozin is clinico-economically feasible in the studied patient population.CONCLUSION: The use of dapagliflozin in addition to standard therapy for the treatment of comorbid patients with CHF and type 2 diabetes is clinically and economically feasible, considering the cost per year of life saved, adjusted for quality of life.

Aim. To assess cost-effectiveness of valsartan+sakubitril, dapagliflosin and empagliflosin for prevention of cardiovascular death and achieving the target indicator "reduction of cardiovascular mortality" of the State Program "Health Development" in patients with heart failure (HF) of the entire profile of left ventricular ejection fraction in 2023-2024Material and methods. The target population was Russian patients who had acute cardiovascular disease (CVD) and a verified diagnosis of HF and received subsidized drug coverage. Parametric modeling was used to predict cardiovascular mortality. In the corresponding comparative pair, the amount of drug costs required to prevent one cardiovascular death (CVD) was calculated, as well as to achieve a 1% target for reducing cardiovascular mortality in the whole country and separately in each region.Results. To prevent one cardiovascular event, the costs of 1-year val-sartan+sacubitril therapy was RUB11,80 million, dapagliflozin — RUB7,07 million, empagliflozin — RUB13,83 million. The costs required to achieve a 1% target for reducing cardiovascular mortality for valsartan+sacubitril, dapagliflozin and empagliflozin were:• in 2023, RUB6534,0 million, RUB3915,0 million and RUB7654,2 million, respectively;• in 2024, RUB1100,6 million, RUB659,5 million and RUB1289,7 million, respectively.Conclusion. The use of dapagliflozin is characterized by the lowest costs for preventing one cardiovascular event and achieving a 1% target for reducing cardiovascular mortality in 2023-2024.

Background. The global recommendations for the treatment strategy of community-acquired pneumonia (CAP) include the empirical prescription of antibiotic therapy (ABT) – beta-lactams, fluoroquinolones, macrolides until the results of laboratory tests are obtained to identify the etiological agent responsible for CAP to determine etiotropic therapy. According to the national Russian clinical guidelines, macrolides, fluoroquinolones, cephalosporins and aminopenicillins are recommended for empirical prescription. Meta-analyses found better outcomes in patients treated with a combination of macrolides with beta-lactam compared to beta-lactam alone. At the same time, the clinical benefit of adding macrolides to beta-lactams for the empirical treatment of moderate CAP remains controversial, since the difference in the results of therapy may depend on the age and comorbid conditions of patients. Objective: to analyze the costs of treating CAP with various ABT strategies in order to optimize the cost structure of a medical organization and plan the budget of local healthcare systems. Material and methods. A retrospective epidemiological analysis of extracts from 157 medical records of middle-aged patients in accordance with the World Health Organization classification treated in multidisciplinary medical organizations was carried out. The methods included frequency analysis, cost of illness analysis, cost minimization analysis, and cost-effectiveness analysis. Depth of research was 2 years. Results. Frequency analysis revealed that the initial strategy of ceftriaxone and azithromycin combination (n=74; 47%) prevailed in prescriptions. In terms of the rate of prescriptions, ceftriaxone monotherapy (n=37; 24%) was in the second place. The analysis of the effectiveness of the selected ABT strategies showed that, in general, 113 (72%) of prescriptions were effective. Standard therapy strategies were equivalent in absolute costs and had a similar cost structure. Conclusion . Doctors’ adherence to national clinical guidelines for CAP treatment was found when prescribing the initial empirical ABT, the dominant strategies were identified. Cost of illness analysis demonstrated that the applied strategies were optimal in terms of cost minimization, and cost-effectiveness ratio. The costs structure in therapy with various ABT strategies did not have significant differences. In medical organizations, they adhere to the most rational and cost-effective strategy for CAP treatment and prescribe ABT regimens in each individual case based on risk factors, as well as the results of studies of CAP pathogens sensitivity.

Multiple myeloma (MM) accounts for 1 % of all cancers and about 10 % of all hemoblastoses. The use of innovative technologies with the inclusion of targeted drugs leads to a significant improvement in the quality of pharmacotherapy and the achievement of overall survival (OS).The aim of the work is to conduct a pharmacoeconomic analysis of the most used MM therapy regimens with the use of targeted drugs and to determine the dominant treatment regimens using a costeffectiveness analysis.Materials and methods. To determine the cost of a course of treatment, we summed up the costs of drugs included in the pharmacotherapy regimen, taking into account taxes, marginal trade markup and duration of the course. Dosing of the targeted drug included in the regimen was determined according to the official instructions for the drug. Progression-free survival (PFS) was adopted as the main criterion for the effectiveness of treatment. Information on PFS of targeted drugs was obtained from data from international phase III RCTs — ASPIRE, TOURMALINEMM1, POLLUX and ELOQUENT2.Results. Based on the results of the pharmacoeconomic analysis, the dominant treatment regimen for MM was determined — daratumumab / lenalidomide / dexamethasone, which has the best cost-effectiveness ratio. The combination of elotuzumab / lenalidomide / dexamethasone was recognized as the least effective technology.

Cephalosporins are the empirical antibiotic therapy (ABT) of choice for patients with community-acquired pneumonia (CAP). When treated with antibiotics, elderly patients, especially those with comorbidities, are at higher risk of developing adverse drug reactions (ADRs). The aim of the study was to analyse data on the safety and efficacy of initial empirical ABT with cephalosporins in elderly patients over 75 years old with CAP admitted to multidisciplinary hospitals in Moscow. Materials and methods . The retrospective study included 305 medical records of patients with CAP admitted to three multidisciplinary hospitals in Moscow in 2017–2019 and prescribed initial mono- and/or combination ABT including a cephalosporin. Initial ABT was considered effective if the body temperature normalised within 48–72 h from the start of treatment. It was considered safe if there were no ADRs during hospital stay. Results . Mostly, patients were prescribed ceftriaxone monotherapy or ceftriaxone and azithromycin combination therapy. These ABT regimens were effective in 69.07% and 78.10% of the cases, respectively. Patients with severe CAP needed their initial ABT adjusted significantly more often than those with non-severe CAP. The initial ABT was changed for a number of reasons, including ineffectiveness, ADRs, abscesses formed as a complication of CAP, sputum culture results enabling causal ABT, secondary hospital-acquired infections, and exacerbated chronic infections. All patients had comorbidities, and the most prevalent were arterial hypertension (83.9%), coronary heart disease (45.6%), chronic heart failure (44.9%), cerebrovascular disease (40.9%), atrial fibrillation (26.9%), diabetes mellitus (21.3%), and chronic obstructive pulmonary disease (19.0%). Initial ABT was significantly more often considered ineffective in patients with chronic heart failure and cerebrovascular disease. The most common causative agent of CAP in the study population was Streptococcus pneumoniae (31.9%). In 16% of patients, the authors identified ADRs associated with the antibiotics used as initial therapy. The most common were diarrhoea, anaemia, leucopenia, and hepatopathy. Ceftriaxone was associated with ADRs in 11% of patients. Conclusions . The study results suggest that initial mono- and/or combination ABT including a cephalosporin is effective and relatively safe; therefore, this treatment option is expedient for elderly patients with CAP. For this population, the safety of ABT may be improved through the wider use of existing markers of ADRs and the identification of new ones.

Aim . To evaluate the cost-effectiveness of achieving the target indicator "Reduction of the cardiovascular mortality of the population" of the State Program "Health Development" when using drugs valsartan+sacubitril, dapagliflozin and empagliflozin in patients with New York Heart Association (NYHA) class II-IV heart failure with reduced ejection fraction ≤40% s in 2023-2024. Material and methods . The target population was Russian patients who received preferential medicines in the last two years after an acute cardiovascular disease. The population size was determined on the basis of Russian literary and statistical sources. To predict the cardiovascular death, a parametric modeling method was used based on published data from clinical trials. The amount of drug costs required to prevent one cardiovascular death, as well as to achieve a one target for reducing cardiovascular mortality, was calculated using each of the comparator drugs in the whole country and separately in each region. Results . The cost of drugs for the 1 st year of therapy to prevent one cardiovascular death in the case of valsartan+sacubitril was RUB 3,99 million, dapagliflozin — RUB 2,63 million, empagliflozin — RUB 4,43 million. There were following costs required to achieve one target indicator for reducing cardiovascular mortality of the State Program "Health Development" for valsartan+sacubitril, dapagliflozin and empagliflozin: in 2023 — RUB 2197,9 million, RUB 1451,5 million and RUB 2435,9 million, respectively; in 2024 — RUB 627,4 million, RUB 407,7 million and RUB 706,9 million, respectively. Conclusion . Among the agents considered, dapagliflozin seems to be the most cost effective for preventing one cardiovascular death and achieving one of the target "Reduction of the cardiovascular mortality" of the State Program "Health Development" in 2023-2024.

Introduction. In multidisciplinary pediatric hospitals in Russia, the prerequisite for the formation of principles of antimicrobial therapy management as a medical technology, implemented with the participation of a clinical pharmacologist became possible on the basis of updated clinical and pharmacological tools proposed by the World Health Organization (WHO) in 2019. Purpose. The project goal is to show the possibilities of control of antimicrobial therapy, as a medical technology in multidisciplinary children’s hospitals to improve adherence to domestic clinical recommendations in the actual clinical practice of implementing antibiotic therapy management programs in children on the profile of «Pediatrics». Material and methods. The pilot scheme was implemented from 2019 to 2021 on the basis of the Morozov Children’s Clinical Hospital by methods of WHO AWaRe and points estimation of prevalence of antibiotic use according to WHO tool checklist in dynamics. Regulatory documents of medical organization (MO) were formed, which ensured transition from traditional to new approaches within 3 years from 2019 to 2021 to maintain clinical practice of antibiotic use based on clinical guidelines. Results. A comparative study of clinical antibiotic use in children “before” the project in 2019 and “after” in 2021 showed a 2.7-fold decrease in antibiotic use by absolute DDDs from 65.99 in 2019 to 24.34 in 2021. DDDs per 100 p/d. By WHO AWaRe method for absolute values of antibiotics in the “Tolerance” category, a 2-fold decrease in consumption and a 5-fold decrease in consumption for absolute values of antibiotics in the “Control” category: in 2019. — 41.13% (abs. 27.55 PDT per 100 p/d) and in 2021. — 60.1% (abs. 4.64 PDT per 100 p/d). Consumption of “Reserve” category antibiotics by absolute values has not changed. Limitations. This publication describes one medical institution in which this project was implemented, which somewhat reduces the value of the results obtained. Conclusion. As a result of the implementation of the principles of managing antimicrobial therapy, this pilot project was able to reduce the irrational use of antibiotics in the pediatric hospital.

Objective : development of approaches to predict the likelihood of adverse reactions (ARs) when using drugs based on a comprehensive assessment of risk factors. Material and methods . We used a database containing 1,450 drug-related ARs reports from January through December 2021. A list of antibacterial drugs by international nonproprietary name (INN) with 4 or more ARs reports was selected as a reference group to perform various types of statistical analysis. A cumulative multivariate regression analysis was carried out on a database of 187 ARs notifications for 13 INN of antibacterial drugs. The study was performed in two stages. In the first stage, a statistical method was used (classical multiple regression, linear discriminant analysis, factor analysis, principal component regression, partial least squares regression, estimation of variance accuracy); at the second stage a modeling method was used. As part of the modeling stage, the integral score of the risk of ARs was presented as a sum of values for individual risk factors. Two groups of risks were proposed to be assessed: 1) intrinsic risk value for each factor (attribute), which was equal to the sum of risks of all factors (conditions) in which the drug had been used; 2) intrinsic risk value for antibacterial drugs by each INN. The total risk value was defined as the sum of the risk of the drug and all factors (conditions) in which this drug had been used. Results . The results were visualized in the form of a two-level risk-based model matrix, with a “heat map” of the risk level overlaid on it. The maximum total risk of ARs was obtained for ceftriaxone – 404.96 points, depending on patient’s gender. The minimum total risk was calculated for azithromycin and cefotaxime depending on the International Classification of Diseases (10th revision) code – 88.46 points. The proposed methodological approach also allows combining all possible combinations of drugs and conditions of their use. For example, for the use of vancomycin in hospital conditions by intravenous administration: intrinsic risk of use – 42.93 points; risk of use in hospital conditions – 183.68 points; risk when administered intravenously – 209.95 points; the total risk value in the designated situation – 436.56 points. Conclusion . The proposed approach can allow medical organizations to reduce significantly the number of ARs when using drugs by categorizing and preventing risks before they occur. It also has significant prospects of application at the federal level, given its modification on a large volume of data.

Objective: to assess budget impact of using empegfilgrastim for the prevention of febrile neutropenia in patients with early and locally advanced human epidermal growth factor receptor 2 positive (HER2+) breast cancer who receive neoadjuvant “docetaxel / carboplatin / trastuzumab + pertuzumab” regimen, considering possible subsequent adjuvant therapy with trastuzumab emtansine or trastuzumab within the Russian healthcare system.Material and methods. We searched and analyzed published clinical, epidemiological and pharmacoeconomic studies as well as regulatory and legal documents. A decision tree model was constructed to reflect the probabilities of switching to different adjuvant therapy regimens depending on the achievement of pathomorphological complete response in patients with early and locally advanced HER2+ breast cancer. The budget impact analysis was carried out comparing two primary prophylactic options, empegfilgrastim and filgrastim.Results. Despite the higher costs of prevention with empegfilgrastim compared to filgrastim (249 vs. 134 thousand rubles), due to the higher rate of achieving a pathomorphological complete response and, accordingly, fewer cases requiring adjuvant therapy with the more expensive trastuzumab emtanzine, savings of 916 thousand rubles per 1 patient per 1 year of therapy are possible. In general, prophylaxis in the target population diagnosed with early and locally advanced HER2+ breast cancer using empegfilgrastim will result in a cost reduction of 9.4 billion rubles per 1 year compared to filgrastim.Conclusion. Empegfilgrastim prophylaxis, despite its higher annual cost, is an efficient option within the Russian healthcare system. In addition to reducing the incidence of febrile neutropenia, the frequency and dose of chemotherapy are preserved, resulting in increased efficacy of the primary therapy.

Aim. To evaluate pharmacoeconomic feasibility using of the tixagevimab and cilgavimab combination for pre-exposure prophylaxis of COVID-19 in immunocompromised patients. Materials and methods. Cost-effectiveness of tixagevimab and cilgavimab in persons 12 years old who weigh 40 kg and have either a history of allergy that prevents their vaccination against COVID-19 or moderate or immunocompromised was assessed based on PROVENT phase III study results. The quantity of life years or quality-adjusted life years gained was calculated. Direct medical cost associated with prophylaxis of COVID-19, treatment of infected patients and those experiencing long COVID post infection were assessed. Results were compared with wiliness-to-pay threshold, measured as tripled gross domestic product per capita and equal to 2.69 mln RUB in 2022. Results. Pre-exposure prophylaxis of COVID-19 results in additional 0.0287 life years or 0.0247 quality-adjusted life years. The cost of additional life year gained is equal to 1.12 mln RUB, the cost of additional quality-adjusted life years is 1.30 mln RUB. Both costs of additional life year and cost of quality-adjusted life years appeared to be significantly less compared to wiliness-to-pay threshold. Conclusion. Pre-exposure prophylaxis of COVID-19 with combination of tixagevimab and cilgavimab is economically feasible and may be recommended for wide use in Russian healthcare system.

We reviewed the role of oxidative stress (OS) in the pathogenesis of ischemic (IS) and hemorrhagic stroke (HS). OS plays a major role in programmed cell death, increased permeability of the blood-brain barrier, astroglial and microglial activation, and local inflammatory response. We also reviewed the current state of neuro- and cytoprotection studies and their translation in clinical practice. With respect to experimental and clinical data the efficacy of long term administration of multimodal cytoprotective drug with antioxidant effect - ethylmethylhydroxypyridine succinate (Mexidol) is discussed during the acute and early recovery period after stroke.

BACKGROUND: The optimization of the pharmacokinetics of antibiotics is an important aspect in improving the effectiveness of therapy for intra-abdominal infections. Thus, studying the survival of experimental animals with a simulated purulent-inflammatory process in abdominal organs using the combined use of antibacterial agents with endolymphatic agents is worthwhile. AIMS: To examine the effect of the co-administration of cefotaxime and hyaluronidase or bovgyaluronidase azoximer on the survival of mice with a purulent-inflammatory process of the abdominal organs. MATERIALS AND METHODS: The purulent-inflammatory process of the abdominal organs, which was simulated by the intraperitoneal administration of a lethal dose of Staphylococcus aureus microbial suspension to mice, was evaluated. Four study groups were formed, with 28 animals each. Group 1 did not receive treatment, group 2 was administered with cefotaxime, and groups 3 and 4 received antibiotics after preliminary administration of hyaluronidase or bovgialuronidase azoximer. For the statistical analysis of animal survival, the Kaplan–Meier multiple assessment method was used, and a univariate analysis using a log-rank test was employed to identify significant differences between the groups. RESULTS: During the study, a single injection of cefotaxime alone and in combination with other studied drugs promoted the survival of some mice with a simulated purulent-inflammatory process of the abdominal organs compared with the untreated group, and at the end of the experiment (day 7), 100% of the animals died. Moreover, the best results were achieved with the initial administration of hyaluronidase or bovhyaluronidase azoximer. Thus, on day 7 of observation, 70% of the animals in groups that received both an antibiotic and hyaluronidase or bovgyaluronidase azoximer survived. No statistically significant differences were found in the effect of these drugs on animal survival in the presence of an experimental purulent-inflammatory process. CONCLUSION: A single injection of cefotaxime alone or in combination with other studied drugs ensures the survival of some mice with a simulated purulent-inflammatory process of the abdominal cavity compared with the control group, in which 100% of the animals died by the end of the experiment (day 7). Moreover, the best results were achieved in groups initially administered with hyaluronidase or bovgialuronidase azoximer.

Aim. To evaluate the contribution ticagrelor compared with clopidogrel therapy in patients with acute coronary syndrome (ACS) and patients with myocardial infarction (MI) to achieving the State Program "Health Development" target "decrease of cardiovascular mortality" in the country as a whole and Russian regions in 2023-2025.Material and methods. In the first year of therapy, all patients over 18 years of age with a confirmed diagnosis of ACS who were indicated for dual antiplatelet therapy (DAPT) were considered as the target population. In the second and third years, therapy was continued by patients at high risk of coronary events after MI. The number of deaths that could be additionally prevented within 1 year after diagnosis using DAPT with ticagrelor compared with DAPT with clopidogrel was calculated based on the PLATO trial. For post-MI patients, the number of deaths that could be prevented in the second and third years of therapy using DAPT with ticagrelor+acetylsalicylic acid (ASA) compared with ASA monotherapy was calculated based on the PEGASUS trial. The proportion of the target "decrease of cardiovascular mortality of the population" in 2023-2025 that can be achieved by using DAPT with ticagrelor instead of clopidogrel or ASA monotherapy was calculated.Results. The use of ticagrelor as part of DAPT for patients with ACS will make it possible (compared to DAPT with clopidogrel or ASA) to contribute to achieving "decrease of cardiovascular mortality" target in the Russian Federation:in 2023 — 8,0% due to expected prevention of 4443 cardiovascular deaths,in 2024 — 30,3% due to expected prevention of 4753 cardiovascular deaths,in 2025, 5366 cardiovascular deaths can be Conclusion. The use of ticagrelor as part of DAPT for patients with ACS will contribute to achieving "decrease of cardiovascular mortality" target in the Russian Federation.

When analyzing pharmacoeconomic studies of the skin melanoma treatment conducted in various countries, the combinations of vemurafenib + cobimetinib and encorafenib + binimetinib are the most acceptable therapy options in terms of increasing life expectancy with adjustments for quality, but, according to the clinical guidelines of the National Joint Oncology Network (NCCN), USA, version 2.2023 – “Melanoma: Cutaneous”, not for adjuvant therapy. At the same time, social networks can be a valuable asset of information about patient’s quality of the life. For the patients with advanced melanoma with a BRAF mutation, the combination of atezolizumab + vemurafenib + cobimetinib indicated the highest clinical effectiveness and can be recommended for pharmacotherapy under condition of drug price reduction.Comparison various drugs combinations with monotherapy for patients with unresectable or metastatic melanoma with a positive BRAF V600 mutation indicated that nivolumab + ipilimumab therapy is not cost-effective in comparison with nivolumab monotherapy, but combination of dabrafenib + trametinib, on the contrary, increases the patient's life expectancy compared to vemurafenib and it’s more cost-effective. It was shown that Pembrolizumab to increase life expectancy but it’s associated with increased costs compared to ipilimumab when comparing different monotherapy options. The assumed additional cost-effectiveness factor is acceptable for most European countries, because it does not exceed the “willingness to pay” threshold. It is necessary to conduct large-scale pharma-economic studies in order to identify the most cost-effective treatment for Russia for various variants of the course of melanoma, both of various combined regimens with each other, and their comparison with monotherapy. It is important to take into account also the costs of correcting undesirable adverse drug reactions, since they have a significant impact to the structure of direct costs. The development of innovative drugs for the treatment of melanoma is proceeding rapidly, however, access to these drugs is limited due to their high cost. Patient-centred drug development and reimbursement options need to be found.

Objective : to evaluate the pharmacoeconomic feasibility of using monoclonal antibodies or their combinations vs standard therapy in patients with mild and moderate-severe COVID-19 in order to prevent the severe course of the disease. Material and methods . The decision tree and Markov models for calculation of costs and outcomes were used for patients with COVID-19 and post-COVID-19 syndrome, respectively. The cost-effectiveness of tixagevimab and cilgavimab was evaluated in persons ≥18 years old not vaccinated against COVID-19 with a high risk of progression to severe COVID-19. Effectiveness and safety of tixagevimab and cilgavimab combination was assessed based on TACKLE phase III study results. The quantities of life years gained (LYG) and quality-adjusted life years (QALY) were calculated. Results were compared with the wiliness-to-pay threshold measured as tripled gross domestic product per capita according the World Health Organization recommendations. Results . Treatment of COVID-19 with tixagevimab and cilgavimab results in additional 0.2657 LIGs or 0.2255 QALYs. The cost of 1 LIG was 213,4 thousand rubles, the cost of 1 QALY was 251,5 thousand rubles. Both costs of LIG and QALY appeared to be significantly less compared to the wiliness-to-pay threshold equal to 3.09 million rubles in 2022. Conclusion . Treatment of mild and moderate-severe COVID-19 is economically feasible and may be recommended for wide use in the Russian healthcare system.