Kulikov Andrey Yurievich

The article deals with the results of validation of the pharmacoeconomic model of emtricitabin/ rilpivirine/ tenofovir (Eviplera) inclusion in highly active antiretroviral therapy of HIV/AIDS in the Russian Federation.

Chronic myelogenous leukemia (CML) is among the nosologies included in the governmental program for supply of medicines to patients with hemophilia, mucoviscidosis, pituitary dwarfism, Gaucher disease, malignant neoplasms in lymphoid, hematopoietic and related tissues, multiple sclerosis, and also after organ and (or) tissue transplantation. Only one medicine, imatinib, is currently available to CML patients within this program. However, 20% to 35% of CML patients have intolerance or develop resistance to imatinib. Therefore, this patient group should receive treatment with the second-generation tyrosine-kinase inhibitors, in particular dasatinib. Pharmacoeconomic analysis is required for dasatinib to be included in the list of expensive medicinal products. This pharmacoeconomic study investigates the use of dasatinib as a second-line CML therapy, based on «cost-effectiveness» and «budget impact» analysis. The study demonstrated that in terms of cost-effectiveness analysis, dasatinib is a strictly preferred alternative as compared to the high doses of imatinib. Moreover, taking into account consumption rate of dasatinib in the real world settings, it is possible to provide treatment to 100% of patients with resistance and/or intolerance to imatinib without additional funding above the total federal budget for CML treatment in 2014.

In this article the economic burden of multiple sclerosis in the Republic of Belarus is presented. Analysis is performed using calculation direct and indirect costs.

In this paper, the main methodological aspects of the willingnessto-pay analysis are highlighted. The values of the willingness-to-pay threshold according to the methodology of the World Health Organization are calculated, the ones of the Russian Federation and the countries of the Group of Twenty and the Commonwealth of Independent States were compared. The international experience of the calculation of willingness-to-pay threshold is covered. Advantages and disadvantages of various methods of calculation of the willingness-to-pay threshold are presented.

The study established a superior clinical efficacy in bleeding episodes relieving, and the health care resources saving in contrast with the current treatment regimen, when patients with von Willebrand disease Haemate P treatment receive. Thus, Haemate P shows pharmacoeconomic advantage over current treatment regimen of von Willebrand disease, which includes coagulation factor VIII drugs, as well as Wilate pharmacotherapy, as the most effective and cheap treatment scheme.

Recent market entry of disease-modifying anti-rheumatic drugs (DMARDs) for patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate in Russia has secured patient access to highly effective treatment options. Access to effective treatment options are of particular importance for highly prevalent conditions with early function impairment such as RA. Innovative medicines, such as DMARDs, are however typically characterized by high treatment costs and require pharmacoeconomic assessment as part of the decision making process regarding federal reimbursement. In the present study, adaptation of an Italian health economic model was performed with the aim to compare cost-efficacy of subcutaneous abatacept versus adalimumab from the Russian Federation national health care system perspective. Clinical efficacy data as well as patient characteristics were based on the AMPLE trial patient population, which was a direct headto-head comparison of subcutaneous abatacept and adalimumab in RA. The time horizon was set at 2 years, which corresponds with the length of the AMPLE study. Direct medical costs included pharmaceutical costs based on the registered maximum selling prices, cost of adverse event treatment, outpatient and inpatient treatment, and diagnostic and laboratory monitoring costs (Rubles, 2015). Results showed that the total 2-year costs of treating 100 patients were 143,750,205.87 rubles for abatacept compared with 165,749,479.26 rubles for adalimumab, at a total cost-savings of treating an entire cohort with abatacept equal to 21,999,273.38 rubles or 219,992.73 rubles per patient. The cost-effectiveness ratios across all disease activity measures (ACR 20, 50, 70, 90; DAS-28; HAQ-DI; CDAI; SDAI) demonstrated that abatacept compared to adalimumab had a lower cost per health outcome. Therefore, from a pharmacoeconomic point of view, subcutaneous abatacept is most likely a preferable alternative compared with adalimumab for the treatment of RA patients in the Russian Federation.

Study purpose: to determine whether canagliflozin is a pharmacoeconomically justified option to be included into therapy for patients with insufficient glycemic control and treated with metformin either as monotherapy administered in the maximum tolerated dose or as a part of a combined therapy with sulfonylurea derivatives taking into account the conditions existing in the Russian Federation.

Currently, in treatment of patients with urothelial transitional cell carcinoma resistant to platinum-based regimen, only Javlor (vinflunine) shows the best evidence when using in second-line chemotherapy scheme. Vinflunine shows the advantage over best supportive care during a randomized Phase III study. The aim of this study is to compare Javlor therapy in combination with the best supportive therapy and the best supportive therapy alone in terms of pharmacoeconomic analysis. Budget impact analysis shows that the treatment of urothelial transitional cell carcinoma with Javlor requires additional expenses. Cost-effectiveness analysis shows that the ICER does not exceed “willingness-to-pay” threshold which means that from the point of view of incremental analysis the therapy in patients with urothelial transitional cell carcinoma using Javlor is cost-effective.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, which, in the cases of high activity, results in extensive damage to various tissues and organs, as well as promotes early patient disability. Most drugs used for the treatment of SLE are currently prescribed off-label, since this specific indication is not reflected in their prescribing information. At the same time, the advent of belimumab (Benlysta®), an innovative biological product for the treatment of SLE, which represents the most severe connective tissue disorder, provided patients with an access to a highly effective targeted therapy, which specifically impacts one of the main mechanisms of the disease. The innovative and proprietary product, Belimumab, has a relatively high cost, which, as the healthcare budget is restricted, requires that a pharmacoeconomic evaluation be completed of combined use of belimumab with standard of care (SoC) versus SoC alone. The present study showed that the use of belimumab combined with SoC in patients with SLE was, clearly, associated with additional costs compared to SoC alone. However, given low incidence of the condition, the overall increase in costs is unlikely to be significant. On the other hand, it was noted that the high belimumab efficacy resulted in lower direct costs of treating the SLE (cardiovascular, cutaneous, and pulmonary) complications, as well as the costs of hospital care. A comparative analysis has demonstrated that the annual cost of treatment with belimumab was similar to the cost of other genetically engineered biological products, which have already been included into the List of Vital and Essential Drugs used for rheumatic diseases, particularly rheumatoid arthritis. In this view, the use of belimumab, which represents the only targeted drug for SLE, could be considered during the review of policy for subsidised drug provision to patients with this condition.

Pharmacoeconomic study of different preparations of botulinum toxin type A used for the treatment of cerebral palsy in terms of health of the Russian Federation was conducted. The aim of this study was to determine the most appropriate therapy of cerebral palsy from the pharmacoeconomic point of view. We compared three regimens: botulinum toxin type A - Dysport® in combination with standard therapy, botulinum toxin type A - Botox® in combination with standard therapy and standard therapy without the use of botulinum toxin. It should be noted that centrally acting muscle relaxant (Baclofen) was used in standard therapy, but BTA in this treatment scheme is not used to eliminate unwanted relaxation of the muscles. As a result, it was found that the regimen Dysport®+standard therapy has the lowest cost-effectiveness ratio (11 608 rubles) in comparison with drug therapy Botox®+standard therapy (12 879 rubles) and standard therapy with a centrally acting muscle relaxant without BTA (25 222 rubles) by the end of 2 years of treatment. According to the budget impact analysis at the end of 2 years for 1 patient the scheme Dysport®+standard therapy was the least expensive form of therapy (1 079 500 rubles) in comparison with therapy Botox®+standard therapy (1 159 085 rubles) and standard therapy with a centrally acting muscle relaxant without BTA (1 210 678 rubles).

This study includes pharmacoeconomic analysis of treatment of patients with severe and moderate ischemic stroke (NIHSS score > 12). The results of data search showed that today an evidential base for these patients treatment exists for cerebrolysin only. The analysis of «budget impact» showed that the transfer of one patient from the basic therapy to the combined therapy with cerebrolysin using gives saving of about 79703 rubles. Therefore the analysis of «costs-efficiency» ratio for the basic therapy with cerebrolysin using demonstrated it to be a dominated technology in comparison with the basic therapy only.

Title: “Pharmacoeconomic Analysis of Ryzodeg®, a Combination of Soluble Ultra-long-acting Human Insulin Analogue (Insulin Degludec) and Ultra-short Insulin Analogue (Insulin Aspart), Use in Therapy of Type 2 Diabetes” Study objective: The objective of this study was to evaluate, whether the use of the combination of basal ultra-long insulin (degludec) and ultra-short insulin (aspart) in the ratio of 70% and 30% in one injection is pharmacoeconomically justified choice for insulin therapy with basal and prandial components for type 2 diabetes mellitus patients with insufficient glycemic control, treated with maximum tolerated doses of metformin in monotherapy.
Materials and methods: Study design – retrospective, modeling. Methods of pharmacoeconomic analysis used are “cost-effectiveness” (“cost–utility”). The modeling horizon was 10 years; the discounting rate was 3%. Alternative comparators included combination of insulin degludec/insulin aspart (Ryzodeg®) and biphasic insulin aspart (NovoMix® 30).
Results: Calculated ICUR ratio showed that incremental cost of 1 additional QALY gained as a result of switching from NovoMix® 30 therapy to Ryzodeg® in addition to metformin therapy equals 519,896 rub. Comparing ICUR with WPS in the RF it can be concluded that Ryzodeg® insulin use is clinico-economically effective in comparison with biphasic insulin aspart. Pharmacoeconomic benefit of Ryzodeg® insulin reflects clinical superiority of the new insulin over the conventional biphasic insulin analogue: possibility to achieve control with a significantly better safety profile, a lower dose of insulin, less pronounced body weight changes and a flexible dosage regimen.

Introduction. On average, about 520,000 cases of acute coronary syndrome (ACS) are registered annually in Russia, and 41,136 patients in 2013 underwent percutaneous coronary intervention (PCI). Every year Russia loses from 100,000 to 120,000 years of life of the working-age population, predominantly male, which leads to a significant loss of the working-age population of the country and presents a significant threat to social and economic welfare of society [8]. The use of more effective antiplatelet therapy in ACS patients can improve outcomes, thus contributing to the reduction in cardiovascular mortality and improving long-term prognosis.
Objectives. The aim of this study was to perform a comparative pharmacoeconomic analysis of ticagrelor + ASA and clopidogrel + ASA therapy in patients with ACS undergoing PCI in the context of the Russian health system.
Results. Analysis of effectiveness revealed that effectiveness of ticagrelor + ASA treatment regimen was higher. Cost-effectiveness analysis showed that ticagrelor + ASA was a dominant therapy considering average prices in Russia by the results of tenders, as well as ticagrelor price planned for registration in the Essential Medicines List and prices for clopidogrel registered in the Essential Medicines List. According to the results of budget impact analysis, the use of ticagrelor + ASA regimen leads to money saving considering average prices in the Russian Federation by the results of tenders, as well as ticagrelor price planned for registration in the Essential Medicines List and price of Clopidogrel registered in the Essential Medicines List.
Conclusion. Therapy of acute coronary syndrome patients managed with PCI with combination of ticagrelor and ASA is economically preferable in comparison with therapy with combination of clopidogrel and ASA

According to the World Health Organization, breast cancer is the most common form of cancer in women worldwide. The steady increase in the prevalence of breast cancer, followed by an increase in the state budget expenditures on drug supply for this category of patients, determines the relevance of pharmacoeconomic evaluation of treatment of HER2-positive breast cancer using a combination of lapatinib and capecitabine and trastuzumab emtansine monotherapy. A subgroup analysis of the therapeutic outcomes in patients with HER2+ breast cancer conducted by the EMILIA study failed to find a statistically significant difference in median overall survival in patients receiving either trastuzumab emtansine or a combination of lapatinib and capecitabine as second-line treatment, or in patients with non-visceral metastases. Analysis of overall survival of the entire population of patients in the EMILIA study revealed that trastuzumab emtansine is more effective than a combination of lapatinib and capecitabine. Despite this, NICE does not recommend treatment with trastuzumab emtansine due to high cost of treatment. The EMILIA study results were used as a basis for pharmacoeconomic models for HER2+ breast cancer therapy, using such methods of pharmacoeconomic analysis as budget impact analysis, cost-effectiveness analysis, and costminimization analysis for these subgroups of patients. Result of budget impact analysis revealed that the use of the lapatinib and capecitabine combination can reduce health system expenditures by 3,985,271 rubles per patient per year or by 5,851,484 rubles over three years per one patient, which allows treating 4 additional patients given the fixed budget. Cost-effectiveness ratio of lapatinib + capecitabine equals to 869,705 rubles and 3,461,960 rubles with LYG and QALY as efficacy endpoints, respectively, which identifies this therapy as cost-effective in pharmacoeconomic terms. Cost-minimization analysis of lapatinib+capecitabine patient groups in the second-line treatment, and a group of patients with non-visceral metastases showed that the use of this treatment may reduce costs by 78% in comparison with trastuzumab emtansine.

Blockade of renin-angiotensin system (RAS) remains one of the most main strategies in treatment of arterial hypertension (AH), and drugs blocking this system, mainly angiotensin-converting-enzyme inhibitor (ACEI) and blockers of receptors to angiotensin II, are the main classes of antihypertensive drugs. The presence of different clinical effectiveness of drugs in these groups, as well as different frequencies of occurrence of undesirable cardiovascular events, side effects and formed the basis of pharmacoeconomic (PE) studies. According to the conducted cost-effectiveness analysis, the treatment regimen using Monopril is characterized by lowest cost and the lowest coefficient of cost-effectiveness ratio in the treatment of patients with AH. The results of the budget impact analysis suggest that therapy with Monopril leads to budget savings. The results of the sensitivity analysis demonstrated the adequacy of the performed pharmacoeconomic analysis and the stability of the obtained data – during the change of the cost factors in the range of ± 97% the therapy with the drug Monopril maintained its advantage expressed by the results of the cost-effectiveness analysis. Сost-effectiveness analysis and budget impact analysis were used in this study. The indirect comparison of two antihypertensive drugs was performed: ACEI (fosinopril, ramipril, lisinopril, perindopril) and ARB II (valsartan, losartan, telmisartan, candesartan). Both groups of drugs are not only one of the main classes of antihypertensive drugs, which can be prescribed to all patients with AH, but also have priority indications, such as diabetes mellitus, metabolic syndrome etc. Results of costs analysis show that fosinopril treatment scheme is characterized with total costs - 22 751 rub., with the lowest cost-effectiveness ratio – 285, during the treatment of AH and budget economy from 5 048 rub. to 46 805 rub. per 1 person per year compared with–ramipril, lisinopril, perindopril, valsartan, losartan, telmisartan, candesartan.

Objective: to assess pharmacoeconomic aspects of treatment substitution of metformin immediate release (IR) form for metformin extended release (XR) form in diabetes mellitus (DM) type 2 treatment in Russian Federation healthcare system.
Methods: retrospective modelling performed according to standardized pharmacoeconomic methods such as: “cost-effectiveness analysis”, “budget impact analysis”, “sensitivity analysis”. Markov model with 20-years time horizon was used to forecast compared therapy methods long-term impact on “cost-effectiveness” results in terms of QALY, direct and indirect costs. Analyzed competitors: Glucophage Long (metformin extended release (XR) form) and three generic metformin immediate release (IR) forms which are in the lead of consumption on Russian market (Siofor, Metformin-Richter, Formetin).
Results: the results of effectiveness analysis QALY-scores were 5.2925 and 4.6479 (20-years horizon with 3% discount rate) for metformin XR and IR forms respectively. While total expenditures are 3169258.07 b for Glucophage Long (XR form) therapy and 3 422 420.90 b, 3 426 951.18 b and 3 439 108.79 b for Formetin, Metformin-Richter and Siofor respectively.
Conclusion: metformin XR using improves glycemic control in comparison to metformin IR, which mediately (according to modelling results) decrease risk of DM complications and, in hence, decrease expenditures. Therefore and due to the most favorable tolerance, Glucophage Long therapy demonstrates the minimal total expenditures with the maximum QALY-scores.

Pharmacoeconomic evaluation of patients with BRAF mutation-positive melanoma treatment with dabrafenib and vemurafenib was conducted in the present study. When analyzing the costs required per one year of the therapy with the drugs being compared, it was established that treatment with dabrafenib was 28% less expensive in comparison with vemurafenib, and the differences in the cost per patient per year was 1,633,622 RUB. The budget impact analysis has shown that dabrafenib comparing to vemurafenib treatment to may reduce budget costs by 1,268,108 RUB per patient within first one year. The results based on data from previous clinical studies have shown that treatment with dabrafenib reduces costs by 35% as compared to the therapy with vemurafenib. Analysis demonstrated that throughout the projected cohort of patients (1245 patients), requiring BRAF-kinase inhibitors treatment, dabrafenib treatment allows to treat additional 680 patients in comparison with vemurafenib within the period before the beginning of progression. Therefore, dabrafenib therapy is preferred treatment option for patients with BRAF mutation-positive advanced and unresectable melanoma in Russian Federation.

The goals of this study was: 1. to evaluate the superior regimen of antiviral drug treatment of chronic hepatitis C (daclatasvir + asunaprevir (a combination of the medicinal products) versus perginterferon alfa + ribavirin or peginterferon alfa + ribavirin + simeprevir or paritaprevir + ritonavir + ombitasvir + dasabuvir) in treatment-naive and treatment-experienced patients (HCV genotype 1b) without liver cirrhosis and with liver cirrhosis based on comparison of cost, effectiveness and safety; 2. To define, using «budget impact» analysis, economic outcomes of including daclatasvir + asunaprevir in current practice of HCV treatment This analysis was performed using two scenarios of the adjusted model “The MONARCH Cost-effectiveness Model”. «Budget impact» analysis was conducted using adapted model «ALLY: Daklinza® (Daclatasvir) Budget Impact Model». The study demonstrated that the first study hypothesis was correct: the combination of the medicinal products for treatment of HCV-infection (HCV genotype 1) daclatasvir + asunaprevir was found to have advantages over the combinations peginterferon alfa + ribavirin, peginterferon alfa + ribavirin + simeprevir and dasabuvir, ombitasvir + paritaprevir + ritonavir in respect of the cost-effectiveness ratio. Furthermore, results of «budget impact» analysis confirmed the second study hypothesis – introduction of DCV + ASV in current practice of HCV treatment will lead to decreasing of complication treatment costs.

This paper represents the results of pharmacoeconomic study of the drug pomalidomide use in treatment of patients with relapsed or refractory multiple myeloma (MM) with more than 50% reduction in M protein, who have received at least two lines of therapy comprising lenalidomide and bortezomib. Lenalidomide and bortezomib were used as comparative treatment options in the study. The pharmacoeconomic study was carried out using the methods for analysis of efficiency, cost, cost-effectiveness, sensitivity and impact on the budget under frame of the medicinal assistance program for people suffering from hemophilia, cystic fibrosis, pituitary dwarfism, Gaucher’s disease, formation of malignant lymphoid haematogenic and related tissues, multiple sclerosis, as well as organ and/or tissue transplants (hereinafter referred to as the Seven Nosologies (VZN) Program). The time horizon of the «impact on the budget» analysis for the “Seven Nosologies” program was consisted of 4 years (2015–2018). The pharmacoeconomic analysis showed that pomalidomide can be recommended for inclusion in the “Seven Nosologies” federal program within the existing budget. From the perspective of the cost-effectiveness analysis, pomalidomide is the dominant option, since the use of pomalidomide in the MM treatment has a significant advantage over lenalidomide and bortezomib therapy in terms of «cost of the average time to disease progression» and «value of survival time». In other words, pomalidomide therapy has the lowest cost of achieved efficiency unit. Analysis of the impact on the budget in case of pomalidomide (Imnovid) inclusion into the pattern of government procurement as part of the “Seven Nosologies” program for the target period (2016–2018) showed that pomalidomide inclusion will not lead to increase the program budget.

As part of this work a pharmacoeconomic study of prophylaxis for febrile neutropenia with granulocyte colony-stimulating factor drugs was carried out. Four prevention schemes of G-CSFs were compared: lipegfilgrastim, pegfilgrastim, filgrastim, lenograstim. As a result, it was found that prophylaxis with lipegfilgrastim is characterized by the lowest “cost-effectiveness” ratio (217,352 rubles) as compared to prophylaxis with pegfilgrastim (342,748 rub.), filgrastim (302,077 rub. for 11 days of prophylaxis), lenograstim (788,582 rub. for 11 days of prophylaxis) by the end of the 1st year of prophylaxis. In the context of budget impact analysis, the least costly scheme was prophylaxis with lipegfilgrastim (211,484 rubles) by the end of the 1st year when calculating per 1 patient. Costs in pegfilgrastim group resulted in 314,986 rubles, in filgrastim group (11 days of treatment) – 264,620 rubles, in lenograstim group (11 days of treatment) – 690,798 rubles. In the context of pharmacoeconomic analysis it is preferable to use lipegfilgrastim for prophylaxis of febrile neutropenia as compared to other G-CSFs (pegfilgrastim, filgrastim, lenograstim), as it allows to increase the number of patients who responded to prophylaxis of febrile neutropenia while reducing costs as compared to other granulocyte colonystimulating factor drugs.