Real Clinical Practice In Russia Research Articles

The choice of optimal therapy for ER+ HER2-metastatic breast cancer (PROMETHEUS): all-Russian analysis of physicians’ preferences – updated survey results

Cyclin-dependent kinase 4/6 inhibitors (iCDK4/6) are the generally accepted standard of care for the treatment of luminal HER2-negative metastatic breast cancer (ER+HER2- mBC). Data from randomized and observational studies have proven the high effectiveness of the combination of iCDK4/6 and endocrine therapy (ET) both in the 1st and in subsequent lines. The use of new drugs in real clinical practice is determined by a number of factors, including the awareness of doctors, their personal experience and subjective preferences, as well as financial support and availability in a particular region. To assess the frequency of prescription of CDK4/6, as well as other types of treatment in the 1st‑2nd line of therapy for ER+ HER2- mBC in real clinical practice in Russia, as well as to determine the factors and preferences of doctors influencing their choice, the National Association of Oncomammologists (NAOM) conducted a survey “Prometheus” of oncology specialists. From February 15 to August 30, 2023, a web survey of healthcare professionals who treat patients with mBC was conducted on the website anketolog.ru. An invitation to survey was sent out through the NAOM database, 112 questionnaires were received and processed. Earlier, in 2020, the “Prometheus” survey was conducted on the territory of the Russian Federation for a similar purpose. In this paper, we present the results of an updated and expanded survey and evaluate changes that have occurred over the past 3 years in actual clinical practice. The results of a 2023 survey conducted in the Russian Federation on the choice of early-line therapy for ER+HER2- mBC showed that, compared with the 2020 survey, the level of “trust” in iCDK4/6 has increased among practicing physicians, and the indications for their use have expanded, including visceral metastases (and even pending visceral crisis), the indications for prescribing chemotherapy in the 1st line have narrowed. When using monoET in the 1st line, the majority of respondents prescribe iCDK4/6 in the 2nd line. Obviously, the wider use of iCDK4/6 is associated not only with the accumulation of clinical knowledge and experience in the use of drugs, but also with improved drug supply. However, the main limitations to the use of iCDK4/6 are still insufficient funding and organizational difficulties. However, it should be noted that 1/5 of the respondents do not face any restrictions and widely prescribe combination therapy.

Durability of first-line antiretroviral treatment in the Russian Federation: retrospective study

Objective. To assess durability of antiretroviral therapy in first line in HIV-infected patients in real clinical practice in the Russian Federation and determine association between basic clinical and demographic characteristics and durability of treatment.Materials and methods. A non-interventional retrospective study was conducted collecting data from primary medical records of HIV-infected patients who signed informed consent form and had started antiretroviral therapy in first line. Patients were enrolled if the third component was a non-nucleoside reverse transcriptase inhibitor (NNRTI) or ritonavir boosted protease inhibitor (PI/r) plus two nucleoside reverse transcriptase inhibitors (NRTIs). Also, patients must have been followed up for at least 96 since start of treatment. Durability of therapy was retrospectively assessed at 48±8 and 96±8.Results. 536 patients were enrolled. Percentage of patients without change of therapy was approximately 76% and 60%, and the mean duration of therapy without changes was approximately 47 and 79 weeks at 48±8 and 96±8 weeks, correspondingly. Durability of treatment was not different for NNRTI+2NRTIs and PI/r+2NRTIs. Only age ≥ 40 years as a basic characteristic was associated with ART change prior to 96 weeks: OR=1.391, 95% CI 1.005-1.925.Conclusions. In real clinical practice in Russia, durability of first-line antiretroviral therapy corresponds published scientific data (in terms of percentage of patients without change of treatment and its duration without change). Durability of treatment and factors associated with its early switch or stop should be investigated in prospective studies further.

Еarly splenic response to ruxolitinib correlates with survival: a russian retrospective multicenter study in patients with myelofibrosis

We retrospectively analyzed the effectiveness of ruxolitinib in patients with myelofibrosis (MF) in real clinical practice in Russia. The study included 42 patients with MF with an average age of 56 years from 10 inpatient and outpatient clinics. The majority of patients (55 %) belonged to the intermediate risk group 1 on the DIPSS scale, 86 % had massive splenomegaly and 88 % had constitutional symptoms. The average initial dose of ruxolitinib was 15 mg twice a day. At the time of analysis, 74 % of patients continued taking ruxolitinib with an average duration of therapy of 20 months. A decrease in the palpable size of the spleen by at least 50 % was recorded in 36 % and 46 % of patients assessed after 3 and 6 months of treatment, respectively. A correlation was found between OV, initial splenomegaly and splenic response after 3 months of therapy. It should be noted that no deaths were recorded in patients with a decrease in the size of the spleen by ≥ 50 %. There were no cases of discontinuation of treatment due to side effects. In general, in our retrospective study, ruxolitinib effectively controlled constitutional symptoms and reduced the size of the spleen in patients with MF. An early splenic response after 3 months of therapy is apparently a prognostic factor for OS, and a decrease in the size of the spleen by less than 25 % should be considered as treatment ineffectiveness in patients with MF taking ruxolitinib.

The use of long-acting insulin degludec in adult patients with type 2 diabetes mellitus in real clinical practice in Russia

BACKGROUND: Effective glycaemic control remains the most important task in managing the risks of Diabetes type 2 complications development. In this regard, the choice of insulin preparations with minimal variability of action is of utmost importance since this approach allows achieving the maximum treatment effectiveness and adequate safety level.AIM: The aim of this study was to investigate insulin degludec treatment effect on glycemic control in adult patients with Diabetes Mellitus (DM) type 2 in a real-world clinical setting in the Russian Federation.MATERIALS AND METHODS: The open prospective study was conducted in 2020–2021 in 35 clinical centers in 31 cities of the Russian Federation. The study included adult patients with type 2 DM treated according to Russian routine clinical practice. The prospective follow-up period was 26 weeks. The main study endpoints were changes in HbA1c level, fasting plasma glucose, insulin daily doses, number, and characteristics of different types of hypoglycaemia episodes and adverse events (AEs), and patient preferences compared to previous treatment.RESULTS: The study enrolled 494 patients. By the end of follow-up period:The mean HbA1c decrease was 1.6% (p<0.0001).Fasting plasma glucose level decreased by 3.4 mmol/L (p<0.0001).Daily basal and prandial insulin doses decreased by 1.6 IU/day (p<0.0001) and 2.1 IU/day (p<0.01), respectively.Severe episodes of hypoglycemia did not occur, while the incidence of nonsevere episodes decreased significantly.76 patients (15.4%) had 105 AEs, of which 41 (in 33 patients, 6.7%) were serious.COVID-19 was the most frequent AE reported in 21 patients (4.3%).Only in one case insulin degludec was withdrawn due to the patient’s pregnancy and the AEs that arose from it.Most patients (98.6%) preferred insulin degludec to previous treatment.CONCLUSION: The study demonstrated a statistically significant improvement in glycemic control, accompanied by basal insulin dose decrease combined with the absence of severe episodes of hypoglycemia, and significant decrease of nonsevere episodes (total and nocturnal). These results led to a large proportion of patients wanting to continue insulin degludec treatment preferring the medicine over previous treatment.

Результаты исследования “Deti-2”: эффективность комбинации глекапревир/пибрентасвир в реальной клинической практике у подростков 12–17 лет с хроническим гепатитом С в России

The introduction of interferon-free combinations made it possible to effectively conduct antiviral therapy of chronic infection caused by hepatitis C virus (HCV) first in adults and later in adolescents. Glecaprevir/pibrentasvir (GLE/PIB) allowed to achieve sustained virological response (SVR12) in 100% (47/47) of adolescents in the DORA clinical trial. In the meantime there is insufficient data describing the effectiveness of GLE/PIB in adolescents in real clinical practice in Russia. Objective. Evaluation of the effectiveness of GLE/PIB in the treatment of chronic hepatitis C in adolescents 12–17 years of age in real clinical practice in the Russian Federation. Patients and methods. This prospective multicenter observational study enrolled adolescents (12–17 years old) chronically infected with HCV who were prescribed GLE/PIB for 8–16 weeks according to the label approved in the Russian Federation. Efficacy was evaluated based on the sustained virological response rate (SVR12), defined as the HCV RNA level < 50 IU/ml (or undetectable) 12 weeks after the last dose of GLE/PIB. Results. Of the 99 patients enrolled in the study, 92 received GLE/PIB for 8 weeks and 7 for 16 weeks. The overall SVR12 rate was 96.77% (90/93). In subgroups receiving 8- and 16-week courses of therapy, the efficacy was 96.51% (83/86) and 100% (7/7), respectively. SVR was achieved in 96.43% (81/84) of treatment-naive patients, and in 100.00% (9/9) of treatmentexperienced patients. Adverse events (AEs) were reported in 7.07% of patients (7/99), while no AEs of the 3rd degree of severity were observed, as well as no serious adverse events. All patients who did not achieve SVR12 had been diagnosed with stage 4 HIV infection. Conclusion. GLE/PIB was highly effective and well tolerated by adolescents infected with HCV in real clinical practice in Russia, which corresponds to the results previously obtained in the DORA clinical trial. Key words: hronic hepatitis C, hepatitis C virus, glecaprevir, pibrentasvir, SVR12, adolescents

Socio-economic burden of newly diagnosed pulmonary arterial hypertension and early specific treatment initiation impact on the costs in real clinical practice in Russia

Socio-economic burden of newly diagnosed pulmonary arterial hypertension and early specific treatment initiation impact on the costs in real clinical practice in Russia

Resolution of the Expert Council on the issues of diagnosis and treatment of myeloproliferative neoplasms, existing standards and the possibility of their implementation in real clinical practice in Russia

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Experience of using gene replacement therapy with Zolgensma® (onasemnogene abeparvovec) in real clinical practice in Russia

Objective: to analyze the safety and evaluate the effectiveness of therapy with onasemnogene abeparvovec in patients with spinal muscular atrophy in real clinical practice based on the experience of using the drug in the neuromuscular center of Research Clinical Pediatric Institute of Pirogov Russian National Research Medical University.Materials and methods. Patients with spinal muscular atrophy received therapy with onasemnogene abeparvovec based on the prescription of the drug according to vital indications by a council of physicians of Federal institutions (the availability of the drug was carried out within the framework of the MAP Program (global program of managed access MAP to AVXS-101 for eligible patients in countries, where it is not approved by regulatory authorities (NCT03955679), through funding from the charitable foundations, as well as through funding from the state fund “Circle of Kindness”. The drug tolerance was assessed and the analysis of side effects after drug administration was based on the criteria for adverse events (General criteria Adverse Event Terminology (CTCAE) v. 5.0) Patient motor function was assessed prior to treatment initiation and every 3–6 months after therapy using the Philadelphia Pediatric Hospital’s CHOP INTEND scale, total motor development based on Hammersmith Hospital Neurological Assessment Scale in Young Children, Part 2 (HINE-2), and the acquisition of new motor skills.Results. 41 children aged 5 to 47 months (weighing no more than 21 kg) received therapy with onasemnogene abeparvovec in the period from April 2020 to December 2021. Adverse events (hyperthermia, decreased appetite, nausea, vomiting) were registered in all patients with different degree of severity. Elevated levels of transaminases greater than 2 times the upper limit of the normal range were observed in 32 patients (78 %), thrombocytopenia in 9 patients (22 %). 15 patients (36 %) required a dose adjustment of corticosteroids.17 patients underwent assessment of motor scales after 6 months, 10 children were assessed after a year. The average improvement on the HINE-2 scale was 3.3 / 4.4 points, respectively. The average improvement on the CHOP INTEND Scale was 7.1 / 9.4 points after 6 / 12 months of therapy.Conclusion. The efficacy and safety of onasemnogene abeparvovec have been demonstrated in real clinical practice in the treatment of spinal muscular atrophy for children in different age groups with a body weight of no more than 21 kg.

Results of a clinical trial of the efficacy and safety of vildagliptin and metformin fixed combination in real clinical practice in Russia (MASTER study)

BACKGRAUND: The widespread prevalence of type 2 diabetes mellitus (T2DM), high mortality and disability of such patients are the reason for the constant active search for effective approaches to hypoglycemic therapy. Recent years have been marked by a change in the strategy for treatment initiation of T2DM. In clinical studies, evidence has been obtained about the benefits of prescribing combination therapy from the time of diagnosis. It seems important to study this treatment option also in real clinical practice.AIMS: To evaluate the effectiveness and safety of the initiation with Galvus Met® as compared with any other combination therapy approaches used in everyday clinical practice.MATERIALS AND METHODS: multicenter prospective observational study in 15 regions of Russia lasting 6 months. Patients were included in the study after the endocrinologist made a decision on the appointment of therapy. Of the men and women over 18 years of age with first diagnosed or previously untreated type 2 diabetes and a level of glycated hemoglobin >7.5%, two groups were formed. The first group included patients who received vildagliptin + metformin (Galvus Met®) in a fixed dose of 50/1000 mg, n=729, the second — another double combination (with the exception of insulin and GLP-1), n=669. The primary endpoint was defined as the proportion of patients (%) who achieved the level of HbA1c <7.0% without proven hypoglycemia at the end of the observation. The NHPQ questionnaire was used to assess the frequency of hypoglycemia.RESULTS: 1385 patients completed the study. For the other combination therapy group, metformin and sulfonylurea derivatives were most often selected (66.5%). In the Galvus Met® group, 68.7% of patients achieved an HbA1c level of <7.0% without proven hypoglycemia, which is significantly better compared to the group of other combinations (40.7%, p <0.001). Galvus Met® therapy contributed to a significantly greater decrease in HbA1c levels by the end of the study compared to other combinations (delta HbA1c -1.6 ± 0.8% versus -1.4 ± 0.9%, p <0.001). In the same group, the average level of HbA1c reached 6.7 ± 0.6% by the end of the study versus 7.1 ± 0.8% in the comparison group, p <0.001. In the Galvus Met® group, body weight decreased by 3.2 ± 3.9 kg, and in the comparison group by 1.3 ± 4.8 kg, p <0.001. The frequency of hypoglycemia episodes in the Galvus Met® group by the end of the study was significantly lower than in the comparison group: 0.8 ± 0.7 episodes per person, versus 1.4 ± 0.8, p = 0.037. In the Galvus Met® group, there were significantly fewer adverse events (4.9% versus 17.7%, p <0.001).CONCLUSIONS: In real clinical practice, Galvus Met® starting therapy has shown better efficacy and safety in terms of achieving glycemic control, HbA1c dynamics, effects on body weight, the frequency of hypoglycemic conditions compared with other combined oral hypoglycemic therapy.

CDK4/6 inhibitors in the treatment of metastatic breast cancer. Choosing optimal therapy for estrogen-receptor-positive HER2-negative metastatic breast cancer: analysis of doctors’ preferences (“Prometheus”) in Russia – first results of the survey

The emergence of a new class of drugs – inhibitors of cyclin-dependent kinases 4/6 (CDK4/6) – has changed the paradigm of treatment of patients with luminal HER2 negative metastatic breast cancer. Their effectiveness is confirmed not only by randomized, but also observational studies on a wide heterogeneous population of patients from daily clinical practice; the use of these drugs in the 1 st line is significantly expanding in the world. On the territory of the Russian Federation, an observational study of Prometheus was carried out, the purpose of which was to assess the frequency of prescribing CDK4/6 inhibitors, as well as other types of treatment in 1–2 nd lines in real clinical practice in Russia, as well as factors and preferences of doctors influencing the choice of therapy. A survey of the target audience, whose answers can be considered reliable and reflecting today’s Russian clinical practice in the treatment of breast cancer, showed that, despite the fact that the overwhelming majority of doctors (78 %) believe that the maximum benefit from the appointment of CDK4/6 inhibitors is expected for the 1 st line therapy, in real clinical practice, only 35 % of doctors practice 1 st line prescription. In the 2nd line of therapy, CDK4/6 inhibitors are prescribed by 45 % of experts, in the 3 rd (or more) line – 20 %. According to the respondents, the main obstacle to the appointment of CDK4/6 inhibitors is the unresolved issues of the availability of therapy (44 %) and its cost (34 %). Among all the proposed clinical criteria, only the criterion “visceral metastases with impaired function of internal organs” influences the decision not to prescribe a combination of hormonal therapy and a CDK4/6 inhibitor in 1–2 nd lines of therapy. Criteria such as ECOG status, menopause status, tumor subtype preceding chemotherapy, timing of progression do not determine the choice when deciding not to prescribe combination therapy.

The efficacy and safety of nusinersen within the expanded access program in Russia

Introduction.Spinal muscular atrophy is a severe neuromuscular disease characterized by rapid progression of muscle weakness and earlydeath. Pathogenetic therapy with nusinersen can significantly change the course of the disease and enable the patient to acquire new skills.The study of the efficacy and safety of nusinersen therapy in patients with type 1 spinal muscular atrophy should be continued.Theaim of the studywas to assess the safety and efficacy of nusinersen therapy in patients with type 1 spinal muscular atrophy for 6 monthsas part of an expanded access program at federal and regional healthcare facilities.Materials and methods.Patients with type 1 spinal muscular atrophy received nusinersen therapy under the expanded access program(NCT02865109). Patients were evaluated before starting treatment and 6 months after starting treatment. Overall motor development andmotor function was assessed using the Hammersmith Infant Neurological Status Scale Part 2 and the Philadelphia Pediatric Hospital Neonatal Motor Scale.Results.41 children aged 6 to 38 months received nusinersen therapy between July 2019 and March 2020. At the time of analysis, all patients were alive and continued treatment. The average improvement on the Hammersmith Hospital Neurological Status Scale was 3.7 pointsafter 6 months of therapy compared to baseline (n = 39, p <0.001). The mean improvement on the Children’s Hospital of PhiladelphiaScale for the Diagnosis of Motor Function in Newborns was 9.8 after 6 months of therapy from baseline (n = 30, p <0.001).Conclusion.The efficacy and safety of nusinersen have been demonstrated in real clinical practice in Russia in the treatment of early-onsetspinal muscular atrophy.

Bladder cancer: treatment after progression. Results of the second retrospective analysis of data on the efficacy of vinflunin in patients with metastatic urothelial cancer in real clinical practice in Russia

Objective. There is the second generalized analysis of administration of vinflunine in real clinical practice in Russia.Materials and methods. This analysis gathered 15 patients with urothelial carcinoma treated using this medicine in 8 cancer centers in Russia. We assessed efficacy, safety profile of vinflunine in this subset of patients.Results. Clinical efficacy of vinflunine (complete response + partial response + stable disease) was 73.3 %, one patient demonstrated complete response. Median of response duration accounts for 3.8 months. Six-month and 1-year survival rate made up 93.3 %. Adverse events were observed in 53.5 %, with only one episode of neutropenia 4 grade.Conclusion. In our second analysis vinflunine was more effective than in randomized clinical trial and other studies from real practice in Europe. Thus, we confirm expediency to administer of vinflunine for metastatic urothelial carcinoma.

Early Response and Long-Term Outcomes of Ruxolitinib Therapy in Myelofibrosis: Multicenter Retrospective Study in 10 Centers of the Russian Federation

Aim. To assess the efficacy of targeted therapy with ruxolitinib in patients with myelofibrosis in real clinical practice in Russia. To determine the prognostic value of spleen reduction in the early stages of ruxolitinib treatment and its effect on overall survival. Materials & Methods. The present retrospective study was based on the data of 10 centers of Russia. It included 56 myelofibrosis (primary or post-polycythemic and post-throm-bocythemic) patients who received ruxolitinib. The median age of patients was 56 years (range 26-76 years). Most of them (59 %) were considered intermediate-1 risk according Results. By the start of data collection most of patients (79 %) had been treated with ruxolitinib. In no case therapy was withdrawn for the reason of drug toxicity. On ruxolitinib constitutional symptoms were reversed in 70 %, 87 %, and 98 % of patients by months 1, 3 and 6, respectively. In 36 % and 46 % of patients by months 3 and 6, respectively, > 50 % decrease in spleen size was observed. Overall, in 31 % and 27 % of cases the size of the spleen decreased by less than 25 % by months 3 and 6, respectively. The factors affecting the changes in spleen size have not been identified. The probability of overall survival by years 2 and 5 of follow-up was 97 % and almost 70 %, respectively. This parameter was significantly affected by the extent of spleen size reduction by month 3 of follow-up as well as by its initial size. Conclusion. Ruxolitinib shows high efficacy for both decrease of general myelofibrosis symptoms and reduction in spleen size. The extent of spleen reduction is an important prognostic factor. It seems, that in patients with insufficient spleen reduction an increase in drug dose is advisable. If it is not possible, alternative methods of treatment should be sought.

Factors affecting the efficacy of gemcitabine and nab-paclitaxel (paclitaxel + albumin) combination in the Russian patient population: results of a multicenter retrospective study

Introduction . The randomized MPACT study showed that nab-paclitaxel plus gemcitabine results in statistically significantly longer life expectancy. The objective of this retrospective study is to obtain relevant data on the efficacy of this combination in real clinical practice in Russia. Materials and methods . The study included patients with morphologically proven locally advanced or metastatic pancreatic cancer, with a general condition assessed on the ECOG scale between 0-2, which received gemcitabine and nab-paclitaxel. Immediate and long-term treatment outcomes were evaluated. Results . 142 patients, who received treatment from 2009 to 2019 in 17 centers from 11 regions of Russia, were included in the study. Assessment of the objective effect was made in 134 patients. Objective effects were detected in 34 (25.4%) cases. The median time-to-progression was 6.1 months (95% confidence interval (CI) 4.8-7.4), the median length of life was 14.2 months (95% CI 10.6-17.9). An elevated CA19-9 level is the only independent adverse prognostic factor for progression-free survival (RR = 8.0, 95% CI 1.4 -43.8, p = 0.02) according to Cox multivariate regression analysis. The number of previously conducted chemotherapy lines (p = 0.34), ECOG status (p = 0.70), age over 70 years (p = 0.45), serious comorbidity (p = 0.97) did not have a statistically significant effect on progression-free survival. Findings . The gemcitabine and nab-paclitaxel combination has a relatively higher efficacy in advanced pancreatic cancer. The immediate and long-term results of its use in real clinical practice in Russia are consistent with data obtained in the Western countries.

Результаты российского наблюдательного исследования EVA PLUS: Применение КОК с фолатами в реальной клинической практике

Результаты российского наблюдательного исследования EVA PLUS: Применение КОК с фолатами в реальной клинической практике

Efficacy and safety of eribulin in HER2-negative metastatic breast cancer: the results of long-term experience in real clinical practice in Russia

Aim. The aim of the study is to examine the efficacy and safety of eribulin in HER2-negative metastatic breast cancer (BC) in Russian clinical practice. Materials and methods. The analysis included 459 patients with advanced BC from 44 federal and municipal medical clinics in Russia and received at least 2 courses of treatment with eribulin in accordance with the registered indications for drug. The average age of women was 56 years (between 29 and 81 years), 83% of patients had HER2-negative tumor subtype (49.9% - luminal BC and 33.1% - triple-negative BC) HER2-positive biological tumor subtype was registered in 17% of patients. Visceral metastases were diagnosed in 73% of patients and three-zone and multiple zone metastases were diagnosed in 41.6% of cases. The median number of prior lines of therapy in patients with disseminated disease was 2; anthracycline and taxane chemotherapy was applied in 94.3% of patients, and 38.1% of patients were recived CT plus capecitabine. Standard treatment regimen with eribulin was cotinuing (1.4 mg/m² as a 2-5-minute intravenous infusion administrated on days 1, 8 of a 21-day cycle) until disease progression, unacceptable toxic effects, or impossibility of the drug administration for any other reason. We estimated the efficacy and safety of treatment with eribulin in Russian patients with HER2-negative BC. Results. Objective response rate was achieved in 20.5% of cases, complete response rate was in 3.2%, partial - 17.3%, and the stable disease rate was marked in 52.7% of women, and in 19.7% of these cases was prolonged more than 6 months. The frequency of objective response was higher in luminal BC group compared with triple-negative BC: 23.5% vs 15.8%; tumor growth control 76.9% vs. 67.8%, respectively; p

PCN179 - THE COMPARATIVE PHARMACOECONOMIC ANALYSIS OF USING DIFFERENT ERYTHROPOIESIS-STIMULANTIG AGENTS FOR MANAGING CHEMOTHERAPY-INDUCED ANEMIA IN ADULT CANCER PATIENTS IN ACTUAL PRACTICE IN RUSSIA

Anemia occurs in 40% of patients undergoing treatment for solid tumors. Aim of this study was to perform cost-minimization analysis of using different erythropoiesis-stimulantig agents (ESA) – epoetin alfa (Eralfon®, biosimilar of Russian origin) and darbepoetin alfa (Aranesp®) – for managing chemotherapy-induced anemia (CIA) in adult cancer patients in actual practice in Russia. Analysis of the published clinical trials was conducted to evaluate efficacy and safety of using different ESA. MS Excel based model of medical care patients with anemia has been developed for 1 patient with solid tumor undergoing chemotherapy taking into account the possibility of individual selection of the dose for epoetin alfa (initial dose 12000 IU 3 times per week) and for darbepoetin alfa (initial dose 500 mcg every 3 weeks) after 4 weeks of treatment. To evaluate the real clinical practice of managing anemia in adult patients undergoing cancer treatment in Russia interview of experts was conducted. To measure costs of treatment chemotherapy-induced anemia for the state budget were used “cost-minimization” analysis. Direct medical costs included drugs, therapy monitoring (Hb concentration), hemotransfusions, side effects correction and were calculated from the Russian healthcare system perspective. A survey of experts showed that the treatment with ESA required the individual selection of the dose after 4 weeks of treatment and using of darbepoetin alfa is associated with a higher risk of thrombosis, hypertension and myalgia. The total costs of treatment CIA per patient were $2111 with epoetin alfa and $3932 with darbepoetin alfa. The difference amounted to $1821 in favor of the epoetin alfa (rate for June 2018). Managing CIA with biosimalar epoetin alfa in adult cancer patients was effective and economically justified treatment option in real clinical practice in Russia.

Therapeutic Drug Monitoring of Antiepileptic Drugs in Real Clinical Practice in Russia

Introduction: Anticonvulsants refer to drugs with interindividual variability of plasma concentrations and clinical efficacy. Therapeutic drug monitoring (TDM) is an important tool for optimizing pharmacotherapy with anticonvulsants in real clinical practice. The aim of the study was to analyze the results of TDM of valproates (VPA) and carbamazepine (CBZ) in epilepsy adults in clinical practice in Russia. Methods: observation study in 800 epilepsy adults (mean age 35.5±0.5) the rate of achievement the therapeutic concentrations (TC) of VPA and CBZ in different drug forms using high performance liquid chromatography; range of TC for VPA 50-150 mg/l, for CBZ 4-12 mg/l. Results: The frequency of achievement TC on VPA was 66.4% in average dose – 1325.1±29.6 mg/day with no difference between sustain-released and immediate-released drug forms. Gender differences of VPA concentrations were identified: women mean Cmin and Cmax were higher than in men with significantly lower daily dose. The frequency of sub-TC VPA was 16.3% and over-TC – 1% (Cmax 164.2±2.4mg/l); the toxic concentration for CNS (175 mg/l) was not achieved. In VPA doses<500mg/day there was no patients with TC; in 1001–1500 mg/day TC have 75%, in doses 1501–2000mg/day – 97%; in >2000 mg/day – 86% and there was high risk of over-TC (4%). The frequency of achievement TC range VPA monotherapy was 2 times more than in combination VPA+CBZ (67% versus 34%). The frequency of achievement TC range on CBZ was 78.6%, the average daily dose was 922.2±23.0 mg/day with significantly higher rate of TC range achievement when using sustain-release forms of CBZ. The frequency of sub-TC CBZ was 6.3%, over-TC – 1.25%. In patients with over-TC mean dose was 1250 mg/day, Cmin 13.5±0.2mg/l, Cmax 15.1±0.7mg/l. At initial doses<600 mg/day 64.3% patients have TC; in doses>600 mg/day – 87%. In daily doses 600-1200 mg and >1200 mg 1.3% and 4.1% patients have over-TC by both Cmin and Cmax, only by Cmax – 8.8% and 18.4%, respectively. Conclusion: the frequency of TC on VPA and CBZ is high with rare cases of over-TC, but there was problem of paradox low concentrations in single cases. CBZ have less predictable concentrations in therapeutic doses range than VPA.

Beta-blockers, and real clinical practice in Russia: the gap between the understanding of the doses of beta-blockers and subsequent prognosis in patients with cardiovascular disease

Presents an analysis of the reception beta-blockers in three epidemiological studies sections of the EPOKhA. Respondents in each slice (2002, 2007, 2017) were stratified into 5 subgroups: only suffering from hypertension - AH (subgroup AH), patients with stable angina pectoris, but in history and clinically has no evidence of acute myocardial infarction (AMI) and chronic heart failure (subgroup of coronary heart disease); after myocardial infarction, but do not have clinical manifestations of chronic heart failure (subgroup myocardial infarction); patients with acute myocardial infarction formed for any reason, but with no previous history of AMI (subgroup chronic heart failure), and patients with clinical manifestations of chronic heart failure after suffering AMI in anamnesis (subgroup myocardial infarction + chronic heart failure). During 15 years in the Russian Federation the frequency of administration of beta-blockers increased from 20% in the section of cardiovascular pathology to 30%. The most sensitive to the use of beta-blockers were patients with a history of AMI and chronic heart failure. Prolonged beta-blockers have been used at the population level only in 2007, but the frequency with any cardiovascular pathology does not exceed the 50% threshold, and the achievement of goals (control heart rate) does not exceed 10% of the level at any pathology. This dependence is associated with low-dose beta-blockers. In any case, the dose of beta-blockers did not exceed 50% of recommended that can be a separate cause of cardiovascular mortality at the population level in Russia.

The Comparative Pharmacoeconomic Analysis of Using Different Agonists of The Thrombopoietin Receptor In Adult Patients With Chronic Idiopathic Thrombocytopenic Purpura In Actual Practice In Russia

To perform cost-effectiveness analysis of using different thrombopoietin (TPO) receptor agonists - romiplostim and eltrombopag - in adult patients with chronic idiopathic thrombocytopenic purpura (ITP) taking into account compliance in the management of them in actual practice in Russia. MS Excel based model of medical care patients with chronic ITP has been developed based on the research hypothesis that the level of patient compliance in certain categories can affect the effectiveness of long-term therapy with different TPO receptor agonists – romiplostim 250 mcg SC once weekly and eltrombpag 50 mg per os once daily. To evaluate the real clinical practice of patients with chronic ITP in Russia interview of experts was conducted. Direct medical costs including drugs, injections, therapy monitoring (CBC, platelet count), rescue treatment, bleeding treatment (grade 3, 4 with the WHO bleeding scale), outpatient visits were calculated for 1 patient for 1 year. The overall platelet response was included into the model as the effectiveness criteria. A survey of experts showed that the using of romiplostim is associated with a higher compliance in patients with a chronic ITP, therefore with a higher efficacy of treatment. The total costs of treatment per patient with chronic ITP within 1 year were $67,468 with romiplostim and $30,975 with eltrombopag. However, taking into account a possible low level of compliance of patients in certain categories in real clinical practice in Russia the cost-effectiveness ratio for romiplostim amounted to $81,287/1 case effectively treatment compared with $110,625/1 case of effective treatment for eltrombopag. The difference amounted to $29,338 in favor of the romiplostim (rate for June 2017). Using of romiplostim in the treatment of adult patients with chronic ITP was effective and economically justified treatment option in real clinical practice in Russia in patients with low compliance.