Diabetes mellitus (DM) is a widespread, severe disease that has outpaced many infectious and non-infectious diseases in terms of both incidence increases and economic burden in most developed countries. In addition to the direct threat to the health and well-being of patients, DM is associated with many severe complications. Among the most significant late complications of DM are diabetic retinopathy (DR) and diabetic macular edema (DME) which can lead to slow, persistent vision loss up to blindness. Significant progress in treating DME has been obtained after the role of vascular endothelium growth factor (VEGF) in the disease’s pathophysiology became more understood, with several powerful clinical options emerging as result. Among the anti-VEGF drugs that have proven themselves well in clinical trials and practice with regards to treating DME are ranibizumab and aflibercept. Since there is currently relatively little understanding of their comparative pharmacoeconomic performance within context of Russian healthcare, the current pharmacoeconomic research (PHe) effort was undertaken. Aim. To perform comparative PHe analysis of ranibizumab and aflibercept for treatment of patients with DME in Russian Federation (RF). Methodology. A Markov model with 3 month long cycles, simulating the changes in patient’s vision acuity was designed for this research effort. For each of the compared therapeutic alternative a simulated group of 1000 DME patients was constructed. The PHe analysis was performed from the point of view of Russian healthcare system within context of Mandatory Medical Insurance system and also from point of view of Russian budget as whole. Randomized controlled clinical trials investigating safety and efficacy of analyzed drugs were used as source of efficacy and safety data. Number of patients who avoided stage IV vision loss (blindness) was used as efficacy criterion. Time horizon of PHe analysis was set at 3 years. Costs were accounted based on existing treatment standards, and literature sources were used to link quality of life and vision acuity and then register QALY for various model states. Modelling results were used to carry out cost-effectiveness analysis (CEA), cost-utility analysis (CUA) and budget impact analysis (BIA). Two single-factor sensitivity analyses (SA) were used to ensure the results are robust to changes in market situation, and an additional analysis was undertaken to test for effects of choice of eye being treated (better seeing or worse seeing). Results. CEA indicated that ranibizumab administered using Pro Re Nata (PRN) regimen has best cost-efficacy, with lowest CER of 1 264 rub. Ranibizumab administered in Treat and Extend (T&E) regimen and aflibercept had higher CERs and thus inferior cost-efficacy (1 403 rub and 1667 rub respectively). The advantage of ranibizumab PRN extended to CUA, in which CUR was 554 rub for ranibizumab PRN, 616 rub for ranibizumab T&E and 729 rub for aflibercept. BIA performed per 100 000 population (accounted for prevalence of DM and DME epidemiology) has found that use of ranibizumab PRN instead of aflibercept could result in budget burden reduction of more than 17 million rubles per 3 years. All SA have confirmed result robustness. Conclusion. These results indicate that ranibizumab demonstrates favorable pharmacoeconomic properties and its further introduction into Russian clinical practice would allow to increase the efficacy of healthcare resource utilization in the RF.

Diabetes mellitus (DM) is a widespread, severe disease that has outpaced many infectious and non-infectious diseases in terms of both incidence increases and economic burden in most developed countries. In addition to the direct threat to the health and well-being of patients, DM is associated with many severe complications. Among the most significant late complications of DM are diabetic retinopathy (DR) and diabetic macular edema (DME) which can lead to slow, persistent vision loss up to blindness. Significant progress in treating DME has been obtained after the role of vascular endothelium growth factor (VEGF) in the disease’s pathophysiology became more understood, with several powerful clinical options emerging as result. Among the anti-VEGF drugs that have proven themselves well in clinical trials and practice with regards to treating DME are ranibizumab and aflibercept. Since there is currently relatively little understanding of their comparative pharmacoeconomic performance within context of Russian healthcare, the current pharmacoeconomic research (PHe) effort was undertaken. Aim. To perform comparative PHe analysis of ranibizumab and aflibercept for treatment of patients with DME in Russian Federation (RF). Methodology. A Markov model with 3 month long cycles, simulating the changes in patient’s vision acuity was designed for this research effort. For each of the compared therapeutic alternative a simulated group of 1000 DME patients was constructed. The PHe analysis was performed from the point of view of Russian healthcare system within context of Mandatory Medical Insurance system and also from point of view of Russian budget as whole. Randomized controlled clinical trials investigating safety and efficacy of analyzed drugs were used as source of efficacy and safety data. Number of patients who avoided stage IV vision loss (blindness) was used as efficacy criterion. Time horizon of PHe analysis was set at 3 years. Costs were accounted based on existing treatment standards, and literature sources were used to link quality of life and vision acuity and then register QALY for various model states. Modelling results were used to carry out cost-effectiveness analysis (CEA), cost-utility analysis (CUA) and budget impact analysis (BIA). Two single-factor sensitivity analyses (SA) were used to ensure the results are robust to changes in market situation, and an additional analysis was undertaken to test for effects of choice of eye being treated (better seeing or worse seeing). Results. CEA indicated that ranibizumab administered using Pro Re Nata (PRN) regimen has best cost-efficacy, with lowest CER of 1 264 rub. Ranibizumab administered in Treat and Extend (T&E) regimen and aflibercept had higher CERs and thus inferior cost-efficacy (1 403 rub and 1667 rub respectively). The advantage of ranibizumab PRN extended to CUA, in which CUR was 554 rub for ranibizumab PRN, 616 rub for ranibizumab T&E and 729 rub for aflibercept. BIA performed per 100 000 population (accounted for prevalence of DM and DME epidemiology) has found that use of ranibizumab PRN instead of aflibercept could result in budget burden reduction of more than 17 million rubles per 3 years. All SA have confirmed result robustness. Conclusion. These results indicate that ranibizumab demonstrates favorable pharmacoeconomic properties and its further introduction into Russian clinical practice would allow to increase the efficacy of healthcare resource utilization in the RF.

Aim. To assess the pharmacoeconomic feasibility of including lenvatinib in the list of vital and essential drugs (VED) and the state program for providing to the necessary drugs to treat patients with differentiated radioiodine-resistant thyroid cancer. Materials and methods. The design of the study is a retrospective analysis of the literature data. Methods of pharmacoeconomic analysis - cost analysis, budget impact analysis, cost-effectiveness analysis. Results. The replacement of sorafenib with lenvatinib when included in the VED list and the state program for providing the necessary medicines for the treatment of patients with differentiated radioiodine-resistant thyroid cancer will reduce the burden on the program budget. At the size of the target group of 100 people for 3 years, the savings will amount to 43.95 million rubles. The total reduction in the load on the budget will be 11.8%. The results obtained are resistant to an increase in the price of lenvatinib by 19.0% and a decrease in the price of sorafenib by 52%. The average cost of therapy for 1 patient with differentiated radioiodine-resistant thyroid cancer for 1 year with the use of lenvatinib in the first line is 36.0% lower than with sorafenib. The savings for 1 year is 334 911 rubles on the patient. In terms of «cost-effectiveness», the drug lenvatinib dominates sorafenib. The CER value per patient for the year using lenvatinib is 48.7% lower than with sorafenib. Conclusion. From the pharmacoeconomic point of view, the use of lenvatinib in the first line of therapy of radioiodide-differentiated thyroid cancer is preferred in comparison with the use of sorafenib. The inclusion of lenvatinib in the list of vital and essential drugs and the state program for providing the necessary drugs is pharmacoeconomically feasible.

The share of antineoplastic drug dossiers submitted to reimbursement in Russia raised from 15% in 2014 to 28% in 2017. The effectiveness and safety of innovative anti-cancer therapy is higher comparing to widely used traditional treatments. At the mean time the costs of innovative anti-cancer care are much higher, which request the incremental costs calculation. Aim. To determine the refence value of incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR). Materials and methods. We analyzed health-economic (HE) studies submitted in the drug dossiers with ATC codes L01 and L02 to the reimbursement in Russia in 2014-2017. Life-years gained (LYG), cost of one LYG and cost of one quality adjusted life-year (QALY) gained we taken from HE studies. Subgroups of drugs included and not included in the reimbursement were compared. The reference cost of one LYG was calculated. Results. The median and geometric mean value of ICER/LYG and ICUR/QALY in the subgroup of drugs included in the reimbursement are 2 335 076 RUR/LYG and 2 343 954 RUR/QALY, consequently. Median and geometric mean of ICER/LYG in the subgroup of drugs included and in the reimbursement are by 33% and 21% lower comparing to the subgroup of drugs not included in the reimbursement. Median and geometric mean of cost of one QALY gained is 2 324 906 RUR/QALY. Conclusion. The reference value of ICER/LYG and ICUR is in the interval 2 300 000 - 2 500 000 RUR.

Aim. Evaluation of the impact on the budget of the program for the provision of necessary medications (ONLS program) for the inclusion of a new drug vedolizumab for the treatment of adult patients with moderate or severe active ulcerative colitis (UC) and moderate or severe active Crohn’s disease (CD). Material and methods. The analysis provides a retrospective study based on published data. Based on the results of the auctions for the purchase of compared drugs, the size of the target population of the patients was calculated in the framework of ONLS. The calculation was carried out taking into account the proportion of drugs used for the therapy of inflammatory bowel diseases (IBD) in the total volume of purchased inhibitors of TNF-a. For the target group identified, the budget load is determined with the gradual replacement of TNFa inhibitors with vedolizumab. The horizon of the study was 3 years. The calculations used the average tender prices for the package of the preparation for 2016. Results. It is established that the cost of 1 year of therapy with vedolizumab is lower than that for infliximab, adalimumab or golimumab. The inclusion of vedolizumab in ONLS implies the subsequent replacement of TNFa inhibitors by vedolizumab: in the first year in 11% of patients with UC and 15% of patients with CD, in the second year in 17 and 32%, respectively, in the 3rd year 28 and 43% respectively. This allows to reduce the budget impact for 3 years for the treatment of UC by 11,9 million rubles, and for CD therapy by 24,1 million rubles. With the increase in the share of vedolizumab on the market by replacing TNFa inhibitors, budgetary savings are increasing. Vedolizumab therapy is the most effective option in the treatment of IBD from a clinical and clinico-economic point of view in comparison with TNFa inhibitors. Conclusion. The inclusion of the drug vedolizumab in ONLS is pharmacoeconomically feasible. The use of vedolizumab in terms of Budget impact Analysis is preferable to the current treatment regimen including infliximab, adalimumab, golimumab and cerolizumab pegol.

Chronic heart failure (CHF) is a disease characterized by a number of typical symptoms, which are related to inadequate blood perfusion of internal organs both at rest and under exercise, which often also leads to liquid retention. It has poor prognosis and constitutes considerable burden on healthcare system. Supramolecular sacubitril/valsartan complex has been shown to significantly reduce frequency of hospitalization and emergency room visits in international RCT's. This indicates that there is a significant interest in performing local, Russian studies focusing on effects of using sacubitril/valsartan may have on healthcare system burden. Methodology. Epidemiological characteristics of patients with CHF receiving “standard” care were assessed. 75 healthcare professionals have been questionnaired to investigate patient parameters and significant event frequency. The study was carried out in 10 large cities of Russian Federation. Effects of switching patients to the new therapy were also assessed. Results. It was confirmed that epidemiological properties of patient population is within parameters found during previous large Russian epidemiological studies. It was found that utilization of sacubitril/valsartan is associated with significant reduction in healthcare resource utilization due to reduction in hospitalizations and emergency service use. Per 3 month of observation, patients receiving standard treatment had average hospitalization frequency of 0,8 and a similar frequency of requiring ambulance dispatch. Switching patients to sacubitril/valsartan resulted in drop of hospitalization frequency to 0,3 (per 3 month of observation) and a similar reduction of ambulance calls. Conclusions. Preliminary analysis of data obtained during this study confirms high efficacy of new therapy using sacubitril/valsartan supramolecular complex within Russian healthcare, specifically regarding reduction of clinically significant unfavorable events such as hospitalizations and ambulance calls. This indicates that this treatment approach has potentially beneficial effect on burden experienced by medical facilities and expedience of carrying out further research in this direction.

The results of the analysis of the cohort of children and adolescents 7-16 years old from the central and northwestern regions of Russia (n=250) are presented. Levels 25(OH)D>30 ng/ml were observed no more than in 6% of participants. The diagnosis E55 «Vitamin D deficiency» was comorbid with diagnoses of bronchial asthma (P=0.003856), nasal congestion (P=0.003016), wheezing (P=0.000133), seasonal allergic rhinitis (P<0.00001), diabetes mellitus (P<10^-10), obesity (P<10^-10), as well as with an increased risk of ankle/foot injuries (P<10^-10) and scoliosis (P<10^-10). A age-dependent scheme for calculating the required dose of vitamin D is presented.

Neurotoxicity is not uncommon in use of the drugs in many therapeutic classes. Manifestations of neurotoxicity vary from ototoxicity, visceral neuropathy and neuromuscular blockade (defeat of the peripheral nervous system) to impaired consciousness, nonspecific encephalopathy, seizures and non-convulsive epileptic status (central nervous system damage). The article presents predisposing factors of neurotoxicity, as well as the mechanisms of its development. On the example of neuroactive drugs (anticonvulsants, anesthetics and psychotropic drugs) their effect in the antenatal period and during lactation is examined. In the post-neonatal period antibiotics play an important role in the neurotoxic effect, in particular, ß-lactams and fluoroquinolones.