Clinical Practice In Russia Research Articles

Phenotypic characteristics of COPD patients with a smoking history in POPE-study in the Russian Federation

Chronic obstructive pulmonary disease is a significant problem for Russian healthcare. The identification of different clinical phenotypes of the disease may allow individualizing approaches to the treatment of patients with this pathology, while there is insufficient data on the phenotypic characteristics of patients with COPD in Eastern and Central Europe. Methods . The article presents data from 356 outpatient patients with COPD with a smoking history of more than 10 pack/years, who were included in the study randomly without prior selection or invitation. 57.6% of persons were patients without frequent exacerbations. Patients with frequent exacerbations were 33.7% (without the presence of chronic bronchitis – 9.3% and with the presence of chronic bronchitis – 24.4%). An overlap of bronchial asthma and COPD was revealed in 8.7% of the included patients. According to the GOLD (2011), 7% of patients belong to group A, 26.4% to group B, 4.2% to group C, and 63.4% to group D. Results . This paper presents the results of the Russian part of the international POPE-study (Phenotypes of COPD in Central and Eastern Europe), which contains data on COPD clinical phenotypes in Russian patients with a verified diagnosis of COPD. A detailed description of spirometric data, comorbid pathology, and prescribed medications depending on clinical phenotypes is given. A high level of administration of inhaled glucocorticosteroids was revealed, which even patients without frequent exacerbations received in 54% of cases. Conclusion . The obtained data will help to develop optimal approaches to eliminate discrepancies between clinical recommendations for managing patients with COPD and actual clinical practice in Russia.

Неинвазивный пренатальный ДНК-скрининг - возможности и перспективы полногеномного подхода

Неинвазивный пренатальный ДНК-скрининг (НИПС) начал использоваться в клинической практике в 2011г. и в настоящее время широко применяется, как и в мире, так и в России. Проанализирована встречаемость «редких» анеуплоидий при проведении полногеномного НИПС у 2061 пациенток и исходы беременностей при наличии таких результатов. Показано, что при анализе всего генома для полногеномного варианта НИПС можно получить дополнительную информацию, важную как для прогноза течения беременности, так и для прогноза плода. Это позволяет выделить дополнительную небольшую группу беременных, которым может быть рекомендовано более пристальное наблюдение в течение беременности или проведение дополнительных диагностических процедур. Однако для определения чувствительности и специфичности определения «редких» анеуплодий и CNV в настоящий момент недостаточно данных. Noninvasive prenatal DNA screening (NIPS) is getting more widespread in clinical practice in Russia and all around the world. The use of shallow whole-genome sequencing for NIPS allows analysis of all chromosome aneuploidies; hence there are large-scale studies only on test performance on common trisomies. This study aimed to analyze the prevalence of «rare» aneuploidies using whole-genome NIPS and pregnancy outcomes in case of a high risk of «rare» aneuploidy. Noninvasive prenatal DNA screening was performed using in house developed protocol. We have analyzed 2061 samples. In 8 cases (0.4%) high-risk of rare trisomy was detected (3 - trisomy 7, 2 - trisomy 8, 1 - trisomy 10, 2 - trisomy 15). We have identified two cases of a high risk of large copy number variations (CNV). For all of the high-risk cases, we have information about pregnancy outcomes. Thereby whole-genome analysis will enable us to get the additional information and reveal pregnancies in need of further observation or testing. Hence there is not enough data for the estimation of sensitivity and specificity of detection of «rare» aneuploidies.

Patients with Combination of Cardiovascular Diseases and Type 2 Diabetes in RECVASA and REGION Registries: Multimorbidity, Outcomes and Potential Effect of Dapagliflozin in the Russian Clinical Practice

Aim. To evaluate the structure of multimorbidity, outcomes and the potential effect of dapagliflozin in patients with a combination of cardiovascular disease (CVD) and type 2 diabetes in Russian clinical practice.Material and methods. The data of 10 registries with the inclusion of 22957 people, including 4370 with type 2 diabetes in 6 regions of the Russian Federation, were analyzed. Scenarios for reducing mortality from all and cardiovascular causes and hospitalizations for CVD were simulated among groups of patients with diabetes combined with myocardial infarction (MI) and diabetes combined with heart failure with reduced ejection fraction (HFrEF) based on data from the Federal Registry of diabetes, the RECVASA and REGION registries, relative risks associated with analyzed adverse events from the DECLARE study.Results. When analyzing the data of all 22957 patients with CVD included in the registries, it was found that the proportion of patients with comorbid diabetes was on average 19.0%. Of the various diagnoses of CVD, the combination with diabetes was most often recorded in patients that had MI – 2.0%, stroke – 22.5% and heart failure – 24.0%. In the RECVASA registry (Ryazan) for 4 years of follow-up of 699 patients with a combination of CVD and diabetes mortality from all causes was 20.9%, and from cardiovascular causes – 15.6%. The simulated number of potentially prevented cardiovascular deaths with dapagliflozin taking in patients with diabetes combined with MI for 4 years in Russia will be 39124, and 37440 cardiovascular hospitalizations. The number of potentially preventable deaths from all causes among patients with diabetes combined with HFrEF will be 4543, cardiovascular deaths in 1995, and the number of prevented cardiovascular hospitalizations will be 7072.Conclusion. According to data from the registries of CVD patients in 6 regions of the Russian Federation, it was revealed that in real clinical practice the proportion of people with comorbid diabetes averaged 19% both at the outpatient and hospital stages. These subgroups of multimorbid patients have both the highest risk of developing fatal and non-fatal cardiovascular complications, and the largest number of indications for prescribing drugs that affect the prognosis due to effects on both CVD and diabetes.

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.

Проспективное мультицентровое исследование применения комбинированного гормонального контрацептива с дроспиреноном

Objective – to determine the satisfaction of patients with the drug DELSIA® used as a contraceptive for 6 months. Design. A prospective multicenter observational programme: the actual clinical practice of using a combined contraceptive Delsia® in female patients of reproductive age for the purposes of contraception. Results. Of 207 women who took part in the programme 204 (98.56%) completed the study. Women who adhered to the drug intake regimen had no pregnancies, which in demonstrative of a high contraceptive reliability of Delsia. Among the women included in the programme, 30% had profuse menstruation,37.3% had painful and 31.9% irregular menstruation, whereas by the end of the 6th month of drug intake these parameters decreased to 0.5, 2.0 and 1.5% respectively (р < 0.001). The average duration of menstrual bleeding decreased from 5.62 ± 1.09 to 3.13 ± 1.37 days (р < 0.001). The frequency of side effects was 23.7% during the first 3 months and 12.7% at the end of the study, and 98.0% of women assessed them as mild or moderate, not necessitating the use of medications. The absolute majority (95.5%) of women expressed a high satisfaction with the drug, assessing it as 4–5 scores on a Likert, the average score being 4.48. Conclusion. The results of studying the administration of the low-dose combined oral contraceptive Delsia in actual clinical practice in Russia have shown a beneficial effect on the characteristics of the menstrual cycle, high scores of drug intake satisfaction, high reliability, safety and compliance. Key words: Delsia, drospirenone, combined oral contraceptives, contraception, ethinylestradiol

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.

Affordability of aprepitant for cancer patients in routine clinical practice in russia: analysis of government-established database

Affordability of aprepitant for cancer patients in routine clinical practice in russia: analysis of government-established database

Implementation of Algorithm-Based Approach for Ph-Negative Myeloproliferative Neoplasms in Routine Clinical Practice in Russia

Implementation of Algorithm-Based Approach for Ph-Negative Myeloproliferative Neoplasms in Routine Clinical Practice in Russia

Real-world study of efficacy, risk management and reasons for discontinuation of natalizumab for treatment of multiple sclerosis in Russia.

BackgroundNTZ is approved in Russia for the treatment of highly active relapsing remitting multiple sclerosis and is reimbursed via federal budget program. However, no data about NTZ treatment in Russia and the effect of federal reimbursement have been performed so far.ObjectiveTo characterize the population of patients receiving natalizumab and assess the efficacy and risk-management plan (RMP) implementation of NTZ therapy in routine clinical practice in Russia.MethodsWe analyzed data for 334 patients, who received at least one infusion of NTZ. Relapse rate, MRI activity, NEDA-3 status after 2 years were assessed. Anti-JC virus antibodies status and RMP implementation were evaluated. Drop-out rate and reasons for therapy discontinuation were analyzed.ResultsPatients switched to natalizumab in Russia are mainly female (63%), with median EDSS score of 3.5 and high disease activity: 93% had at least 1 relapse and 58% had both T1Gd+ and new T2 lesion a year before therapy initiation. Introduction of federal reimbursement allowed patients with less relapses to start therapy with natalizumab. The only predictor of 6-month progression was EDSS score at the baseline of therapy (HR = 2.1375, 95%CI 1.0026–4.5570, p = 0.0492). 82% patients reached NEDA-3 at 24 month of therapy. 25% of patients discontinued NTZ for reasons: tolerability (14.5%), JCV antibody status (61%), and patient’s decision (17%). RMP was implemented in only 36% patients.ConclusionNatalizumab appeared to have high efficacy in Russian clinical practice. Federal reimbursement allowed less active patients to start natalizumab. More efforts should be done to improve RMP implementation.

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

Toxic epidermal necrolysis as a variant of severe skin lesions in systemic lupus erythematosus

Toxic epidermal necrolysis (TEN) has been long believed to be the most severe manifestation of drug allergy. However, cutaneous changes as TEN in systemic lupus erythematosus (SLE) were first described in the late 1970s. As of now, the English-language literature published reports of 30 cases of such lesions in SLE. This paper describes a clinical case of TEN as a direct manifestation of SLE; the positive experience has been first depicted in using not only intravenous immunoglobulin, but also rituximab with a good therapeutic effect in Russian clinical practice.

Intravitreal therapy of diabetic macular edema in Russian Federation: current state of the problem

Currently there is a significant increase in the incidence of diabetes mellitus all over the world, and Russia is not an exception. With the increase in patients with diabetic retinopathy, also rises the incidence of diabetic macular edema, which can lead to persistent loss of vision and disability dramatically affecting the quality of life. Antiangiogenic therapy that is effectively used all over world has specific features for clinical practice in Russia because of its high cost, insufficient public funding, low patient compliance, remoteness of patients from the places of medical care, and low awareness of both patients and doctors about the treatment effectiveness and required regimen. All these problems slow the adoption of this progressive treatment method. Analyzing the causes of low adoption of antiangiogenic therapy and proposing new ways to solve these problems can help reduce the rate of blindness and disability caused by eye complications of diabetes mellitus in Russian Federation, particularly in young and working population.

IMPACT OF ANTIEPILEPTIC DRUGS ON COGNITIVE FUNCTIONS IN CHILDREN AND ADOLESCENTS

The article presents modern points of view on the assessment of сognitive functions of the children and adolescents with epilepsy who take antiepileptic drugs (AEDs). The authors compare various AEDs which are used in modern clinical practice in Russia and abroad, their impact on cognitive functions, discuss the psychometric tools which are used in Russia to assess the dynamics of cognitive functions in this group of patients.

OLANZAPINE FOR THE PREVENTION AND TREATMENT OF CHEMOTHERAPY-INDUCED NAUSEA AND VOMITING

Chemotherapy-induced nausea and vomiting (CINV) has tremendous negative impact on daily life of cancer patients and their quality of life. In this article we analyzed current clinical guidelines in preventive measures and treatment of CINV as well as efficacy of recommended standard regimens for CINV prevention in patients receiving high emetogenic chemotherapy (HEC). We summarized existing data about olanzapine – affordable antipsychotic agent with potent antiemetogenic activity which is quite useful for CINV prophylaxis in patients receiving HEC. We highlighted possible future directions for research of olanzapine in oncology and reasons that preclude integration of this drug in routine clinical practice in Russia.

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.

Assessing methodological quality of Russian clinical practice guidelines and introducing AGREE II instrument in Russia.

BackgroundThere are multiple organisations in Russia that publish clinical practice guidelines (CPGs). The demand for CPGs and appreciation of their role in healthcare provision has been steadily growing. However, quality and methodology of development of CPGs have not been systematically addressed.AimTo analyse the quality of Russian-produced CPGs for surgical treatment of hepatic-pancreatic-biliary diseases.MethodsWe searched Russian databases for CPGs, published between 2013 and 2017. We identified 6 relevant documents that met our inclusion criteria. We approached four experts in the field with written and verbal instructions on the use of the AGREE II questionnaire.ResultsAll six CPGs received the highest domain scores for the domain Clarity of Presentation (46%–80%). The lowest domain scores were for the domain Editorial Independence (6%-25%). Overall, the experts put the highest total sum scores to the CPG for treating chronic pancreatitis (70%), while the lowest total sum score was attributed to the CPG for treating acute cholangitis (22%).ConclusionsThe overall quality of CPGs, as assessed by the four experts with the AGREE II instrument, was low. The highest scoring, best organized and most comprehensive and straightforward CPG was the one for chronic pancreatitis. The AGREE II instrument should be considered for use in Russia by guideline developers to assess existing CPGs and inform the creation of new guidelines.

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.

The effectiveness, safety and economic rationality of the neoadjuvant chemotherapy with biosimilar of Trastuzumab in HER2+ breast cancer in Russian clinical practice.

e12656Background: The biosimilar of trastuzumab (Herticad ®) used in Russian clinical practice since March 2016, but the effectiveness, safety and economic rationality of biosimilar of trastuzumab ...

Study of rivaroxaban for venous thromboembolism prophylaxis after lower extremity fractures in Russian clinical practice

The purpose of the study was to evaluate the efficacy and safety of rivaroxaban in patients after surgical treatment for the lower extremity fractures. Patients and methods. Retrospective multicenter study included 663 patients with femur fractures, 43 patients with complications after total hip arthroplasty (periprosthetic femur fractures, recurrent dislocation) and 10 patients with shinbone fractures. The majority (81.99%) of patients were elderly or senile. In postoperative period all patients received a standard prophylactic dose of anticoagulants. Out of them 75 (main group) - rivaroxaban (10 mg/day), 241 (control group) - other drugs (enoxaparin - 40 mg/day and dabigatran etexilate 150 or 220 mg/day). The efficacy of prophylaxis was assessed by clinical picture and Doppler ultrasound scans. Results. Average bed day made up 9.28. During hospitalization no cases of PE were recorded. In the main and control groups the rate of deep vein thrombosis with clinical manifestations made up 1.89 and 3.31%, respectively. No cases of fatal bleeding occurred. Signs of continuous bleeding in the area of surgical intervention (soaking dressings or recurring wound hematomas) in the main group was recorded rarely (3.15%) than in the control one (8.29%). Conclusion. Reduction of VTE rate with no increase in bleeding risk indicates the feasibility of rivaroxaban use for postoperative PE prophylaxis in patients with lower extremity fractures.