Kulikov Andrey Yurievich

professor of Department of organization of medical provision and pharmacoeconomics, I.M. Sechenov First Moscow State Medical University Moscow,Russia
Komarov E.A., Kulikov A.Y. 5435

Although there have been improvements in the detection and treatment of breast cancer (BC) it remains the most common cancer in women and oneof the leading causes of death. In Western Europe and North America, breast cancer is the leading cause of death among women aged 35 to 54 years (20%), and the second leading cause of death in women aged over 55 years exceeded only by cardiovascular diseases. Breast cancer incidence increases with age, beginning from 40 years, with a peak at 60 to 65 years. The objective of this study was to determine, from the pharmacoeconomic point of view, the preferred treatment regimen (Kadcyla, lapatinib + capecitabine, trastuzumab + capecitabine, capecitabine), used in the treatment of HER2-positive breast cancer, on the basis of comparison of cost-effectiveness ratio, safety and life quality. The use of Kadcyla in the treatment of patients with HER2-positive breast cancer resulted in the highest values of life years gained and quality adjusted life years in comparison with lapatinib + capecitabine, trastuzumab + capecitabine, or capecitabine regimen. According to the results of the costeffectiveness analysis and cost-utility analysis it was found that the therapy with Kadcyla required higher costs to achieve LYG and QALY compared to those of the treatment regimens with the use of lapatinib + capecitabine, trastuzumab + capecitabine, and capecitabine, respectively. Incremental ratios in both analyses are higher than the willingness to pay threshold values for the Russian Federation.

Kulikov A.Y., Ursu E.P. 5383

Main points on financing of healthcare at the regional level are presented, the interrelation between expenditures of regional budgets and the working-age mortality, between the average duration of one case of the temporary disability and the level of public satisfaction with the quality of healthcare is showed. A brief description of the analysis was performed, the types of behavior were highlighted, the results were presented and common trends were emphasized.

Babiy V.V., Kulikov A.Y. 5385

The aim of this study was to determine optimal medical technique based on assessing cost and efficacy of treatment of von Willebrand disease using blood clotting factor concentrates (blood clotting factor VIII + von Willebrand factor): Wilate, Haemate P, Immunate. It was determined that in studies on assessing the efficiency of the concentrates more than 95% of patients rated hemostasis excellent/good. However, the studies were based on different scales of efficiency assessment, different vWF:RСo doses and different data for vWD patients (severity of the disease), therefore the efficiency of blood clotting factor concentrates might be not equal. Results of present study with the assumption about equality of groups, that were analyzed in studies on assessing the efficiency of the concentrates (although, studies on Wilate included more severe patients),evidence that prescribing blood clotting factor concentrate Wilate lead to cost savings compared to the older generation products.

Babiy V.V., Kulikov A.Y. 5328

In this study, a pharmacoeconomic analysis of chronic lymphocytic leukemia therapy in previously untreated patients was conducted, using treatment regimens obinutuzumab (Gazyva) + chlorambucil and rituximab +chlorambucil. The results of the study showed that though the costs of the first treatment course with obinutuzumab + chlorambucil are significantly higher, this regimen reduces the cumulative cost of subsequent therapy lines in patients with CLL (due to a longer progression-free survival). In the end of the third year of therapy, cumulative costs become relatively similar: with the use of the obinutuzumab + chlorambucil regimen, the cumulative cost per 1 patient/year will be 38,390 rubles higher compared to the rituximab + chlorambucil regimen. At the same time, the obinutuzumab regimen showed a lower cost-effectiveness ratio, i.e. it had an advantage over the alternative technology.

Kulikov A.Y., Protsenko M.V. 5345

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.

Kulikov A.Y., Strunina (Rybchenko) Y.V. 5276

Follicular lymphoma is a disease requiring effective therapy that helps to improve a patient’s quality of life. In this study, a comparative analysis of subcutaneous administration of MabThera versus intravenous MabThera was performed. Considering that the formulations are equally effective, a cost minimization analysis was carried out, which showed that transition from intravenous to subcutaneous MabThera resulted in savings of 35,847 rubles per one patient during the treatment course due to the decreased drug administration expenses, medical staff costs, and expenses for hospitalization or day-time staying. The use of the subcutaneous formulation can also prevent economic damage caused by loss of the drug remaining in the vial with the use of the intravenous formulation where the dose depends on the body surface area.

Komarov E.A., Kulikov A.Y. 5304

Breast cancer (BC) is the most common type of cancer in women and one of the leading causes of death among women worldwide, including our country. According to the World Health Organization, over 11,000,000 women with diagnosed BC receive care and treatment worldwide. Each year approximately 1,200,000 new cases of breast cancer are registered and more than 500,000 women die, and it is estimated that the incidents will increase up to 1,450,000. The objective of this study was to determine a treatment regimen (pertuzumab+trastuzumab+docetaxel or placebo+trastuzumab+docetaxel) more advantageous from the pharmacoeconomic point of view, used in the treatment of HER2+ metastatic breast cancer (mBC), on the basis of comparison of costeffectiveness ratio, safety and life quality. The results of the cost-effectiveness analysis showed that cost-effectiveness ratios (effectiveness criterion – Life Years Gained, LYG) were as follows (over a period of 25 years: 1,823,530 rubles in the pertuzumab+trastuzumab+docetaxel group and 587,120 rubles in the placebo+trastuzumab+docetaxel group. The incremental costeffectiveness ratio for the health technologies compared was 8,150,535 rubles/LYG. The results of the cost-utility analysis showed that the cost-utility ratios (utility criterion – Quality Adjusted Life Years, QALY) were as follows (over a period of 25 years): 2,716,738 rubles in the pertuzumab+trastuzumab+docetaxel group and 908,787 rubles in the placebo+trastuzumab+docetaxel group. The incremental cost-effectiveness ratio for the health technologies compared was 10,187,748 rubles/QALY. The results of the budget impact analysis demonstrated that for the Perjeta-trastuzumab-docetaxel treatment regimen, the difference in the required budgetary funds was 5,711,668 rubles in comparison with the placebo-trastuzumab-docetaxel treatment regimen per treatment of one patient with BC (over a period of 25 years).

Kulikov A.Y., Novikov I.V. 5214

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.

Kulikov A.Y., Snegovoy A.V., Ugrekhelidze D.T. 5213

This article deals with pharmacoeconomic study of erythropoietin use in patients with chemotherapy-induced anemia. Four treatments were evaluated, i.e. Epoetin alfa, Epoetin beta, Epoetin theta and Darbepoetin alfa. The results of pharmacoeconomic analysis show that use of Epoetin theta (Eporatio) is the most cost-effective regimen for anemia treatment in cancer patients. Cost-cutting upon patient’s transition to Eporatio amounts up to 9,129 rubles (transition from Epoetin beta), up to 13,812 rubles (transition from Epoetin alfa) and 165,527 rubles (transition from Darbepoetin alfa). Budget impact analysis demonstrated a possibility of total cost-cutting in the amount of 197,075,449 rubles if purchase share of Eporatio increases to 30% via reducing purchase share of Epoetin alfa by 15%, Epoetin beta by 13% and Darbepoetin alfa by 2%.

Kulikov A.Y., Tishchenko D.G. 5174

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.

Kulikov A.Y., Ugrekhelidze D.T., Yagudina R.I. 5113

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.

Alferova I.P., Velednitskiy V.B., Vinoglyadova S.V., Voronin S.V., Golihina T.A., Goroshko L.V., Davydova A.N., Zhukova T.P., Irinina N.A., Kapustina N.K., Kuzin A.V., Kulikov A.Y., Lukina N.V., Mardanova A.K., Maryashina T.M., Matulevich S.A., Mihalchuk V.V., Nelyubova Z.G., Nikonov A.M., Pushkina M.A., Sahar O.V., Strunina (Rybchenko) Y.V., Teunaeva M.M., Hramihina S.S., Chesnokova M.A., Shelkova E.V., Erbis G.A., Yudintseva T.V., Yagudina R.I. 5152

Phenylketonuria is a hereditary disease associated with a metabolic disorder of amino acids in the organism, the prevalence of which in the Russian Federation is 1:10000. Currently, the main treatment of phenylketonuria is diet therapy with specialized health food (a mixture of amino acids without phenylalanine). This research presents the results of a comparison of diet therapy with medicinal mixtures of MDmil PKU line taken from the first month of life of a child compared to food of other producers, taken in later periods. Efficiency analysis is based on data provided by the major regional genetics specialists from 24 regions of the Russian Federation on treatment of 1088 children suffering from phenylketonuria. Cost analysis of treatment of patients with PKU until their majority reveals least expensive diet therapy initiated from the first month of life with specialized health food of MDmil PKU line compared with diet, started in later periods with specialized products of different manufacturers. During the “cost-effectiveness” analysis and the “cost-utility”analysis indicators of CER and CUR are identified showing that when used from the first month of life diet therapy with MDmil PKU line compared with diet, started in later periods with various manufacturers, it is easy to determine treatment of the first group of children as dominant. Budget impact analysis shows that diet therapy with specialized health food of MDmil PKU line in treatment of phenylketonuria can achieve cost savings of 34% to 38% depending on periods of commencement of the diet.

Abdrashitova G.T., Kulikov A.Y. 5103

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.

Kulikov A.Y., Serpik V.G. 5106

Pharmacoeconomic study comparing luteinizing hormonereleasing hormone agonists (LHRH-A), used for prostate cancer treatment was conducted. The study included drugs: buserelin, goserelin, triptorelin and leuprorelin. Pharmacoeconomic study included the following methods:cost analysis, cost-effectiveness analysis, cost minimization analysis and budget impact analysis. The time horizon for cost analysis, cost minimization analysis and budget impact analysis amounted to 1 year, whereas for costeffectiveness analysis it was equal to 6 months. Direct costs were taken into account. As a result, it was found that annual costs for the treatment of one patient for each of the considered drugs (buserelin, goserelin, triptorelin and leuprorelin) respectively accounted for 55 169 rubles, 90 130 rubles, 90 133 rubles и 94 599 rubles. Results of the budget impact analysis showed that the annual budget per patient using drug therapy buserelin, goserelin, triptorelin and leuprorelin respectively amounted to 129 545 rubles, 164 506 rubles, 164 509 rubles and 168 974 rubles. Cost minimization analysis demonstrated that under the assumption of equal clinical effectiveness review of medications, annual treatment of one patient using buserelin is characterized with 34 961 rubles compared with goserelin and 39 430 rubles compared with leuprorelin. Cost-effectiveness analysis using the criterion of decreasing the prostatespecific antigen (PSA) level, it was found that buserelin is characterized with the greatest rate of decrease in the PSA value, so it has the smallest value of the cost-effectiveness ratio and, thus, relative to the comparison drugs is strictly preferred drug.

Babiy V.V., Kulikov A.Y. 5031

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.

Zinchuk I.Y., Kulikov A.Y. 5039

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.

Komarov E.A., Kulikov A.Y., Pochuprina A.A. 4949

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.

Babiy V.V., Kulikov A.Y. 4896

The objectives of this study were to determine the most advantageous antiviral therapy option for chronic hepatitis C (CHC) (peginterferon alfa + ribavirin (PegIFN + RBV) 48 weeks (F0–F4), peginterferon alfa + simeprevir + ribavirin (PegIFN + SMV + RBV) 24 weeks (F0–F4), peginterferon alfa + sofosbuvir + ribavirin (PegIFN + SOF + RBV) 12 weeks (F0–F4), dasabuvir + ombitasvir/paritaprevir/ritonavir (Dasabuvir + Ombitasvir/ paritaprevir/ritonavir) 12 weeks (F0–F3) and dasabuvir + ombitasvir/ paritaprevir/ritonavir + ribavirin (Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV) 12 weeks (F4)) among treatment-naive and treatment-experienced patients (HCV genotype 1) based on the comparison of cost-effectiveness ratios and economic outcomes (“budget impact” analysis) from implementing the treatment strategy PegIFN-α + SOF + RBV instead of PegIFN-α + RBV, PegIFN-α + SIM + RBV and Dasabuvir + Ombitasvir/paritaprevir/ritonavir. Model-based pharmacoeconomic analysis has been conducted. The costeffectiveness analysis showed that independently of the former treatment experience of CHC (genotype 1) patients the combination PegIFN-α + SOF + RBV was a predominant regimen as compared to PegIFN-α + RBV and PegIFN-α + SMV + RBV. In the groups of patients without cirrhosis and with cirrhosis the highest QALY value was noted for Dasabuvir + Ombitasvir/ paritaprevir/ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV combinations, respectively. Also a smaller cost-effectiveness ratio (CER) relative to the two above regimens was noted for PegIFN-α + SOF + RBV. In the group of treatment-naive patients without cirrhosis incremental costeffectiveness ratio (ICER) of Dasabuvir + Ombitasvir/paritaprevir/ritonavir vs PegIFN-α + SOF + RBV was higher than willingness-to-pay threshold (WPT), whereas in the group of patients with cirrhosis ICERDasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV vs PegIFN-α + SOF + RBV was lower than WPT. Using “budget impact” analysis it was shown that switching to PegIFN-α + SOF + RBV from PegIFN-α + RBV regimen will involve extra direct costs for antiviral treatment (AVT), but will lead to a reduction in medical aid costs to the patients not reaching SVR, patients with CHC complications and, as a consequence, will lead to a reduction in cumulative medical costs. Moreover, transition from PegIFN-α + SMV + RBV, Dasabuvir + Ombitasvir/paritaprevir/ ritonavir and Dasabuvir + Ombitasvir/paritaprevir/ritonavir + RBV to PegIFN-α + SOF + RBV will lead to a reduction in both AVT costs and cumulative medical costs.

Kulikov A.Y., Pochuprina A.A. 4894

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.

Arinina E.E., Kulikov A.Y., Tolordava G.A. 4877

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.

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Babiy V.V., Kulikov A.Y. 5031

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.

Kulikov A.Y., Protsenko M.V. 5345

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.

Kulikov A.Y., Tishchenko D.G. 5174

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.

Kulikov A.Y., Ugrekhelidze D.T., Yagudina R.I. 5113

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.

Zinchuk I.Y., Kulikov A.Y. 5039

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.

Kulikov A.Y., Pochuprina A.A. 6045

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.

Kulikov A.Y., Novikov I.V. 5214

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.

Kulikov A.Y., Strunina (Rybchenko) Y.V. 4819

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.

Komarov E.A., Kulikov A.Y., Pochuprina A.A. 4949

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.

Kulikov A.Y., Ugrekhelidze D.T. 5774

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).

Abdrashitova G.T., Kulikov A.Y. 5103

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.

Kulikov A.Y., Novikov I.V. 6497

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.

Kulikov A.Y. 22143

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

Kulikov A.Y., Petrovskiy A.V., Skripnik A.R., Strunina (Rybchenko) Y.V. 4857

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.

Arinina E.E., Kulikov A.Y., Tolordava G.A. 4877

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.

Kulikov A.Y., Novikov D.E. 5649

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.

Kulikov A.Y., Pochuprina A.A. 4894

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.

Babiy V.V., Kulikov A.Y., Shestakova I.V. 4826

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.

Kulikov A.Y., Tishchenko D.G. 5819

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.

Kulikov A.Y., Larionova V.B., Snegovoy A.V., Ugrekhelidze D.T. 5974

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.

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Professor of the Department of organization of drug supply and pharmacoeconomics, leading researcher pharmacoeconomic studies of the Laboratory Research Institute of Pharmacy, First MGMU them. IM Sechenov. Moscow, Russia