Cost-utility analysis and budget impact analysis of pegvisomant for the treatment of adult patients with acromegaly in Poland

Background: The aim of this publication was to evaluate the cost-effectiveness and financial consequences of pegvisomant (PEG) in the treatment of adult patients with acromegaly, who have had an inadequate response to surgery and/or radiation therapy and in whom an appropriate medical treatment with somatostatin analogues (SSA) did not normalize IGF-1 concentrations or was not tolerated compared with SSA continuation. Methods: The Markov model constructed in TreeAge Pro with 45-year time horizon was used in the cost-utility analysis (CUA). Quality adjusted life years (QALY) were used as the measure of effectiveness. CUA was conducted from the perspective of the public payer for health services (Polish National Health Fund, PNHF) and from the patient’s and PNHF’s perspective. Budget impact analysis was performed in a 3-year time horizon from PNHF’s perspective. Two scenarios were compared: “present”, without reimbursement of PEG; “new”, after reimbursement of PEG. Results: The cost of gaining an additional QALY by replacing SSA with PEG is equal 742,724 PLN/ 714,800 PLN (172 470 €/ 165 986 €) from PNHF/PNHF+patient perspective. The annual expenditure of the PNHF’s budget in the first three years would increase by approximately 11.95 million PLN in the first, 26.39 million PLN in the second and 26.5 million in the third year of PEG reimbursement. Conclusion: The creation of drug program for acromegalic patients, in which reimbursement of PEG will be provided, will significantly inf luence the prognosis, course of the disease and improve the patient’s quality of life. Introduction Acromegaly is a rare, chronic disease caused by excessive production of growth hormone (GH). The most common cause of excessive GH production is pituitary tumor. This leads to changes in the external appearance with the enlargement of: facial skins, hands and feet, as well as the growth of internal organs and bones and many systemic complications that cause significant deterioration of the quality of life and consequently lead to premature deaths. [1] The prevalence of acromegaly varies from 50 to 70 cases per million. The incidence rate is 4 million year (both in Poland and in the world), with the same frequency in both gender. The peak of diagnoses is 40-50 years old. In Poland, approximately 2,000 people suffer from acromegaly. [2, 3] The mortality rate in patients with acromegaly is widely quoted to be 2-2.5 times higher than that of the general population. The untreated patients have a shorter life expectancy of an average 10 years, and mortality from cardiovascular, respiratory and a cancer disease is 2-4 times higher than in the general population. [1, 2] The main goal of treatment is normalization of growth hormone (GH) and insulin-like growth factor 1 (IGF-1), followed by removal or reduction of pituitary tumor. [1] Pegvisomant is an analogue of human growth hormone that has been genetically modified to be a growth hormone receptor antagonist. Inhibition of growth hormone action with pegvisomant leads to decreased serum concentrations of insulin-like growth factor-I. [4] In the European Union, pegvisomant is indicate for the treatment of adult patients with acromegaly who have had an inadequate response to surgery and/or radiation therapy and in whom an appropriate medical treatment with somatostatin analogues did not normalize IGF-1 concentrations or was not tolerated. [4] Guidelines of the Polish Society of Endocrinology indicate the possibility of using pegvisomant as monotherapy or the use of pegvisomant in combination with somatostatin analogues. In addition, they indicate that the GH receptor antagonist pegvisomant normalize IGF-1 concentration in more than 90% of patients, thus leading to clinical improvement and alleviation of metabolic disorders (increasing insulin sensitivity improves carbohydrate metabolism). [1] Therapy with an analogue of human growth hormone – pegvisomant in the treatment of acromegaly has already been recommended and reimbursed in most European countries. The objective of this project was to conduct economic analysis (cost-utility analysis, CUA) and budget impact 3 Cost-utility analysis and budget impact analysis of pegvisomant for the treatment of adult patients with acromegaly in Poland analysis (BIA) of pegvisomant for the treatment of adult patients with acromegaly who have had an inadequate response to surgery and/or radiation therapy and in whom an appropriate medical treatment with somatostatin analogues did not normalize IGF-1 concentrations or was not tolerated compared with SSA continuation as part of drug program. The survey was conducted in accordance with the Polish Agency for Health Technology Assessment and Tariffs (AOTMiT) recommendations. [5] Material and methods The decision problem was formulated in accordance with the PICOS scheme (population, intervention, comparator, outcomes, study design) and drug program: Population: adult patients with acromegaly, who have had an inadequate response to surgery and/or radiation therapy and in whom an appropriate medical treatment with somatostatin analogues did not normalize IGF-1 concentrations or was not tolerated; Intervention: pegvisomant (PEG), a loading dose of 80 mg should be administered subcutaneously under medical supervision, following this, patients were given pegvisomant at doses of 10 mg daily (dose adjustments should be based on serum IGF-1 levels); Comparator: continuation of treatment with ineffective somatostatin analogues (SSA); Outcome: quality-adjusted life years (QALY); impact on the payer’s budget; Study design: head-to-head randomized controlled trials (RCT) conducted in parallel groups. Due to the rarity of the indication, observational studies, including patient records, was the main source of pegvisomant effectiveness. The exchange rate of Polish National Bank (2018-11-22) was 1€ = 4.3064 PLN. The size of the target population was calculated on the basis of PNHF data concerning the frequency of highdose SSA in the treatment of acromegaly, expert opinion and the percentage of patients, who have previously received surgery or radiotherapy [6]. Figure 2 showed the methods of calculating the target population. Based on epidemiologic data, a minimum and maximum estimation variant of the target population was also calculated. Analytical technique Due to the statistically significant differences in the response to treatment defined as normalization of serum IGF-1 concentration (main outcome presented in clinical effectiveness assessment of PEG) a cost-utility analysis was performed using the Markov decision model constructed in TreeAge Pro. As the measure of effectiveness, QALY was used and the result was presented as incremental cost-utility ratio (ICUR). ICUR expressed the cost of gaining one additional unit of QALY in case of replacing SSA with PEG. The BIA calculations were made in an MS Excel® spreadsheet. Perspective and time horizon CUA analysis was conducted from the perspective of the public payer for health services (Polish National Health Fund, PNHF) and from the patient and PNHF perspective. Based on the identified economic analyses with similar PICOS, a 20-year time horizon was adopted. [7, 8] Budget impact analysis was performed in a 3-year time horizon from the perspective of the public payer for health services (PNHF). This assumption is consistent with the AOTMiT guidelines. [5] Model structure of CUA In the Markov decision model, the following states, which are important from economic or clinical point of view, were taken into consideration: “IGF-1 normalized”, “IGF-1 non-normalized”, “discontinuation of pegvisomant therapy” (only the first cycle)” and “death” (Figure 1). For example, in the arm with an available option of using pegvisomant, the patient may start the simulation with an answer to PEG, maintain control of IGF-1 concentration, survive the cycle and start the next with preserved disease control or begin, as a non-responder, in the same cycle to discontinue pegvisomant therapy and die from general causes, thus completing the simulation. The length of the model cycle, corresponding to the frequency of health state changes in patients, is one year. Based on the AOTMiT guidelines a discount rate of 5% for costs and 3.5% for benefits was used. [5]