COST-EFFECTIVENESS AND BUDGET IMPACT ANALYSIS OF NILOTINIB FOR THE SECOND LINE TRATMENT OF CHRONIC MIELOID LEUKEMIA IN THE RUSSIAN FEDERATION Avxentyev N. A. 1 , Frolov M. Y. 2 , Makarov A. S. 3 1 Research Institute of Finance and Russian Presidential Academy of National Economy and Public Administration, Moscow, Russia 2 Volgograd State Medical University of the Ministry of Health Russian Federation and Interregional Association of Clinical Pharmacologists, Volgograd, Russia 3 Interregional Association of Clinical Pharmacologists, Volgograd, Russian Federation PCN 90 ISPOR Europe 2018, Barcelona, Spain, 10-14 November, 2018 BACKGROUND ● As of 2016, the majority of patients on active treatment for chronic myeloid leukemia (CML) in Russia are receiving imatinib (5 500 out of 7 000) which makes it the most widely used drug for CML treatment in Russia [1]. However, some patients are resistant or intolerant to imatinib. ● 2 nd generation tyrosine kinase inhibitors (TKI) nilotinib, dasatinib and bosutinib are available for these patients, however only dasatinib is currently included in the Government Drug Reimbursement Program (GDRP) [2], which due to affordability effectively limits the treatment options for Russian patients. OBJECTIVES The aim of the current paper is to conduct pharmacoeconomic evaluation of nilotinib, dasatinib and bosutinib for the 2 nd line treatment of patients with CML from the Russian healthcare system’s perspective. METHODS ● We proposed a Markov model of CML progression on nilotinib, dasatinib or bosutinib 2 nd line therapy. Model included 5 states: 2 nd line treatment, discontinuation (which refers to discontinuation due to adverse event or loss of complete hematological response, major cytogenetic response, progression as assessed by clinical study investigator, excluding progression to accelerated phase or blast crisis), accelerated phase (AP), blast crisis (BC) and death (figure 1). ● Transition probabilities were derived from published clinical trials of the considered drugs [3-5]. We used progression-free and overall survival estimates, which were both corrected on Russian natural mortality rate. Additionally, progression-free survival on dasatinib was re-estimated due to differences in approaches of censuring data between nilotinib, bosutinib [3, 5] and dasatinib [4] trials. ● Due to limited long term clinical data we applied a 4-year time horizon with 3-months cycle length. All costs were discounted at 5 % rate, as proposed by the the Russian guidelines for pharmacoeconomic research [6]. ● Model was used to calculate per patient medical costs, including 2 nd and 3 rd line medication costs (the later corresponds to discontinuation health state), adverse event treatments, inpatient and outpatient care. ● Cost-effectiveness and budget impact analyses were conducted with all costs and health states specific to Russia in accordance with the local guidelines for the pharmacoeconomic research [6]. ● Budget impact was defined as the difference in GDRP costs of treating eligible patients with nilotinib or bosutinib, compared to dasatinib. ● To estimate the number of patients for the budget impact analysis we assumed that all patients who are currently treated with high-dose imatinib (> 400 mg/daily), have an unmet need of nilotinib, dasatinib or bosutinib. We also considered patients, who currently receive any 2 nd generation tyrosine kinase inhibitor in the 2 nd line CML treatment. The resulting sum was multiplied by 40 % (assumption), since not all patients are eligible for reimbursement through GDRP – the program that provides benefits only to certain groups of the Russian population (figure 2). RESULTS The patient distribution during the 4-year modeling period is shown in figure 3. Use of nilotinib, dasatinib and bosutinib resulted in 3.66, 3.56 and 3.69 life-years saved, respectively. Monthly medication costs of nilotinib were US$ 2,626 1 , which were $ 54 (2.0%) less, compared to dasatinib and US$ 1,011 (27.8%) less compared to bosutinib. 4-year total medical costs of nilotinib were US$ 70,336, or 13.9% less compared to dasatinib and 37.3% less compared to bosutinib (table 1). Nilotinib also had the lowest cost / effectiveness ratio: 19 224 US$ per life-year saved, compared to 22 919 and 30 445 US$ per life- year saved for dasatinib and bosutinib, respectively (table 2). If 996 patients (fig. 2) have access to nilotinib through Government Drug Reimbursement Program, 4-year budget spending on drugs will be US$12.4 million (-12 457 US$ x 996 patients) less, compared to dasatinib. DISCUSSION ● A primary limitation of the study was the lack of head-to-head trials of nilotinib, dasatinib and bosutinib, or trials with similar designs that could have been used to conduct an adjusted indirect comparison (such as a network meta-analysis) ● Results of this study were driven by clinical outcomes from trials, which design is usually more conservative in terms of patient characteristics and disease management, compared to real-world practice ● A strength of this economic study was that it considered 3 options, available for the 2 nd line CML treatment in Russia CONCLUSIONS International clinical guidelines indicate that the second generation TKIs are interchangeable in the management of second-line CML patients [7]. This pharmacoeconomic analysis resulted in nilotinib as a cost-saving option in the second-line treatment of patients with CML compared to treatment with dasatinib and bosutinib from a Russian healthcare perspective. LITERATURE 1. Turkina A. G. et al. “Chronic Myeloid Leukemia Patient Registry in the Russian Federation: From Observational Studies to the Efficacy Evaluation in Clinical Practice.” Clinical oncohematology 10.3 (2017): 390–401 (in Russian). 2. State drug registry of the Ministry of Health of the Russian Federation. URL: https://grls.rosminzdrav.ru/Default.aspx (in Russian) 3. Giles, F. J., et al. “Nilotinib in imatinib-resistant or imatinib-intolerant patients with chronic myeloid leukemia in chronic phase: 48-month follow-up results of a phase II study.” Leukemia 27.1 (2013): 107-112. 4. Shah, Neil P., et al. “Long-term outcome with dasatinib after imatinib failure in chronic-phase chronic myeloid leukemia: follow-up of a phase 3 study.” Blood 123.15 (2014): 2317-2324. 5. Gambacorti‐Passerini, Carlo, et al. “Bosutinib efficacy and safety in chronic phase chronic myeloid leukemia after imatinib resistance or intolerance: Minimum 24‐month follow‐up.” American journal of hematology 89.7 (2014): 732-742. 6. Russian Guidelines for pharmacoeconomic research. URL: https://rosmedex.ru/wp-content/uploads/2016/12/MR-KE%60I-23.12. 2016.pdf (in Russian) 7. Bacarini M et al. “European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013”. Blood 122(6):872-884 1 Here and after 1 USD = 62.154 RUB as of June 2018 Figure 1. Markov model of CML progression Note: AP – acceleration phase, BC – blast crisis Figure 2. Number of patients for budget impact analysis Note: TKI – tyrosine kinase inhibitors. Source: Authors’ calculations based on [1] Figure 3. Patient distribution Source: Authors’ calculations Table 1. 4-year treatment costs, US$ per patient Nilotinib Dasatinib Bosutinib Difference: nilotinib - dasatinib Difference: nilotinib - bosutinib 2nd line drug therapy 66 949 79 406 109 800 -12 457 -42 851 Adverse events treatments 295 207 288 88 7 3rd line drug therapy 2 207 1 332 1 484 875 723 Inpatient care 719 566 548 153 172 Outpatient care 166 139 145 27 21 Total 70 336 81 650 112 264 -11 314 -41 928 Source: Authors’ calculations Table 2. Cost-effectivness analysis, US$ per life-years saved Nilotinib Dasatinib Bosutinib Costs, US$ per patient 70 336 81 650 112 264 Life-years saved (LYS), years 3.66 3.56 3.69 Cost-effectiveness ratio (CER), US$ per LYS 19 224 22 919 30 445 Source: Authors’ calculations Copies of this poster are for personal use only and may not be reproduced without written permission of the authors