New Epidemiological, Clinical and Economic Data for Patients With Acromegaly in Bulgaria.

Background: Acromegaly and its comorbidities affect the patients' quality of life, each healthcare system and the society. This study aimed to evaluate clinical characteristics and treatment patterns and the economic burden of acromegaly. Materials and methods: All patients with acromegaly treated with expensive medicines and regularly followed up at the main expert clinical center for acromegaly in the country were included in this nationwide, retrospective, observational, population-based study. Patient characteristics, treatment patterns, healthcare resource use, and costs were assessed for 1-year period (01.01.2018-31.12.2018). Results were processed through statistical analysis using MedCalc software version 16.4.1. Results: A total of 191 acromegaly patients were observed. Approximately 67% were female, 45.5% were between 41 and 60 years and the mean age at diagnosis was 40.73 years. Surgical treatment was preferred as a first-line therapy among almost 89% of all diagnosed patients. The level of comorbidities was very high as more than 95% suffered from at least one concomitant disease. The most frequent comorbidities were other endocrine and metabolic diseases (96.7%), followed by cardiovascular diseases (70.7%). The most common first-line pharmacotherapy was long-acting somatostatin analogs (SSA) (38%) followed by dual combination SSA + pegvisomant (21%). The total economic burden of acromegaly was estimated to be 2,674,499.90 € in 2018 as the direct costs (medication costs, hospitalization costs covered by the patients and the National Health Insurance Fund) outnumbered indirect costs (loss of productivity due to hospitalization): 2,630,568.58 € vs. 43,931.32 €. The average annual per-patient direct and indirect costs were 14,002.62 €. Conclusions: The current study demonstrates a significant clinical and socio-economic burden of acromegaly in the country. Proper diagnosing and regular follow up of acromegaly patients in a specialized pituitary center ensure appropriate innovative pharmacotherapy with achievement of disease control.

Incretins and SGLT-2i Therapy of Type 2 Diabetes - Real Life Study of Their Therapeutic and Economic Effects.

AIM: Incretins [dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide 1 RA (GLP-1 RA)] and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) groups are now routinely used for type 2 diabetes therapy and comprise a large number of medicinal products. The long term therapeutic and economic effect of the incretins' and SGLT-2i in real life setting is not well documented. The goal of the current study is to analyze the cost and results of incretins and SGLT-2i based therapy for type 2 diabetes in Bulgaria. METHODS: The study uses information about the changes in glycated hemoglobin (HbA1c) level from the National diabetes register for 6122 patients and cost paid by the National Health Insurance Fund (NHIF) for diabetes complications, and medicine prices. RESULTS: The results show that after the therapy patients achieved excellent diabetes control. There were no HbA1c values less than 6% before treatment. After the therapy, 3356 people showed values less than 7% HbA1c. It is considered very good diabetic control. The number of people with HbA1c above 8% is decreasing significantly. The number of people with values above 9% is decreasing by almost four times. HbA1c level decreases with the highest percentage for the patients treated with GLP-1 RA, followed by those treated with DPP-4i and SGLT-2i. For a year NHIF reimbursed 5.25 million BGN for incretins and SGLT-2i therapy. NHIF can save between 306 and 510 thousand BGN from incidents that have not occurred as a result of 5 years of therapy. CONCLUSION: Incretins [dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA)] and sodium-glucose linked transporter-2 inhibitors (SGLT-2i) therapy steadily decreases the HbA1c level, and risk of developing diabetic incidents is reduced to between 333 and 465 cases among 6122 treated patients. Avoided cost for therapy of diabetes incidents account for between 305 and 510 thousand BGN.

Pilot Study on the Cost of Some Oncohematology Diseases in Bulgaria.

The goal of the current study is to perform a pilot study of the cost of some oncohematology diseases in Bulgaria. This is a pilot broader burden of disease research. The official report of the National health insurance fund provided information about the total expenditures paid for medicines, ambulatory services, and hospitalizations in 2015 and 2016. To evaluate the costs from a patient perspective, an internet inquiry was organized with the support of the patient organization. The inquiry contained questions regarding the patients' demography, type of oncohematology disease, year of diagnosis, quality of life (EuroQol v5D), and additional out of pocket expenditures. Quality of Life data were statistically analyzed and Kruskal-Wallis analysis of variance was performed. From 2015 to 2016 the number of patients with oncohematological diseases decreased by approximately 3000 people. Less than 30% were hospitalized and the hospitalization cost decreased, but the cost for medicines increased by nearly 1.5 million Euros. Cost for medicines almost tripled the hospitalization cost. The reported mean quality of life was 0.749 (SD 0.203). There was positive correlation between QoL and current disease state (p = 0.008) and age (p = 0.025). 42% reported to have additional expenditures related to their oncohematology disease, 22% reported other expenditures (diet, change of everyday habits etc.) and 42% reported to have productivity loses due to loss of employment or change of work, 44% of the respondents reported additional payment for medicines for concomitant diseases. Thus, the total cost (public funds and patients) accounted for 37,708,764 Euro. Despite the high public expenditures, the indirect costs due to productivity loses are higher. Costs for medicines are higher than costs of inpatient treatment, but this tendency is observed in all European countries. The increases in the costs of medicines are compensated by reduced costs of hospitalization. Despite their higher costs, newer medicines are an effective and reasonable investment from a societal perspective. Currently the higher levels of copayment increase the burden on the patients.

Quality of Life and Cost Study of Rheumatoid Arthritis Therapy With Biological Medicines.

Biological medicines are considered as a cornerstone in the therapy of rheumatoid arthritis (RA). They change the course of the disease and improve the quality of life of patients. To this date there has been no study comparing the quality of life of and cost of RA therapy in Bulgaria. This fact is what provoked our interest toward this research. The aim of this study is to analyse the cost and quality of life of patients with RA threated with biological medicines in Bulgaria. This is an observational, real life study of 124 patients treated with biological medicines during 2012-2016 at the University hospital "St. Ivan Riskli" in Sofia, specialized in rheumatology disease therapy. Patients were recruited after their consecutive transfer from non-biological to biological medicines. The yearly pharmacotherapy cost was calculated with tocilizumab (n = 30), cetrolizmab (n = 16), golimumab (n = 22), etanercept (n = 20), adalimumab (n = 20), rituximab (n = 16). Three measurements of the quality of life (QoL) were performed with EQ5D-at the beginning of the therapy, after 6 months and after 1 year of therapy. Both section of EQ5D were used-VAS and EQ5D questionnaire. Cost-effectiveness was calculated for unit of improvement in EQ5D score for a one year period and decision model was built with TreeAgePro software. The observed cost of therapy varied between 12 thousand Euros for tocilizumab to 6 thousand Euros for rituximab. All biological medicines let to substantial increase in the quality of life of the patients. Patients on tocilizumab increased their QoL from 0.43 to 0.63 after 1 year; on cetrolizumab from 0.32 to 0.56; on golimumab from 0.41 to 0.67; on etanercept from 0.45 to 0.62; on adalimumab from 0.43 to 0.57; on rhituximab from 0.46 to 0.66. The cost-effectiveness estimates of different biological therapies also varied between 66 to 30 thousand Euros for unit of improvement in the EQ5D during one the course of the year. Therapy with biological medicines improves statistically significant the quality of life of patients, measured through VAS and EQ5D scales. Despite the improvement in the quality of life all biological medicines appears not to be note cost-effective due to their high incremental cost-effectiveness ration (ICER). Rituximab's incremental ratio has (ICER) falls closer to the three times gross domestic product per capita threshold and should be considered as preferred alternatives for RA therapy. In general we can conclude that the treatment of rheumatoid arthritis with biologicals improves quality of life significantly. Only rituximab was cost-effective.

Chronic Hepatitis C-Related Cirrhosis Hospitalization Cost Analysis in Bulgaria.

OBJECTIVE: HCV infection is a leading cause of chronic liver disease with long-term complications-extensive fibrosis, cirrhosis, and hepatocellular carcinoma. The objective of this study is to perform cost analysis of therapy of patients with chronic HCV-related cirrhosis hospitalized in the University Hospital "Queen Joanna-ISUL" for 3-year period (2012-2014). METHODS: It is a prospective, real life observational study of 297 patients with chronic HCV infection and cirrhosis monitored in the University Hospital "Queen Joanna-ISUL" for 3-year period. Data on demographic, clinical characteristics, and health-care resources utilization (hospitalizations, highly specialized interventions, and pharmacotherapy) were collected. Micro-costing approach was applied to evaluate the total direct medical costs. The points of view are that of the National Health Insurance Fund (NHIF), hospital and the patients. Collected cost data are from the NHIF and hospitals tariffs, patients, and from the positive dug list for medicines prices. Descriptive statistics, chi-squared test, Kruskal-Wallis, and Friedman tests were used for statistical processing. RESULTS: 76% of patients were male. 93% were diagnosed in grade Child-Pugh A and B. 97% reported complications, and almost all developed esophageal varices. During the 3 years observational period, patients did not change the critical clinical values for Child-Pugh status and therefore the group was considered as homogenous. 847 hospitalizations were recorded for 3 years period with average length of stay 17 days. The mortality rate of 6.90% was extremely high. The total direct medical costs for the observed cohort of patients for 3-year period accounted for 1,290,533 BGN (€659,839) with an average cost per patient 4,577 BGN (€2,340). Statistically significant correlation was observed between the total cost per patient from the different payers' perspective and the Child-Pugh cirrhosis score. CONCLUSION: HCV-related cirrhosis is resource demanding and sets high direct medical costs as it is related with increased hospitalizations and complications acquiring additional treatment.

Clinical characteristics, treatment patterns, and socio-economic burden of COPD in Bulgaria.

BACKGROUND: While the impact of COPD in Western-Europe is known, data from Eastern-Europe is scarce. This study aimed to evaluate clinical characteristics, treatment patterns, and the socio-economic burden of COPD in Eastern-Europe, taking Bulgaria as a reference case. METHODS: A representative sample of Bulgarian patients with COPD was randomly chosen by pulmonologists, based on the following inclusion criteria: COPD diagnosis with at least 1 year of living with COPD, ≥40 years of age, and use of COPD medication. Patient characteristics, treatment, quality-of-life, healthcare resource use, and costs were systematically assessed. RESULTS: A total of 426 COPD patients were enrolled. Approximately 69% were male, 40% had occupational risk factors, 45% had severe and 11% had very severe COPD. Mean CAT scores were 13.80 (GOLD A), 21.80 (GOLD B), 17.35 (GOLD C), and 26.70 (GOLD D). Annual per-patient costs of healthcare utilization were €579. Yearly pharmacotherapy costs were €693. Indirect costs (reduced and lost work productivity) outnumbered direct costs three times. CONCLUSIONS: Bulgaria has relatively high percentages of (very) severe COPD patients, resulting in considerable socio-economic burden. High smoking rates, occupational risk factors, air pollution, and a differential health system may be related to this finding. Eastern-European COPD strategies should focus on prevention, risk-factor awareness, and early detection.

Economic consequences of the vaccination against hepatitis A in the Bulgarian healthcare setting.

The purpose of the present analysis is to calculate and compare the costs and results of the implication of the inactivated vaccine against hepatitis A virus (HAV) in the Bulgarian healthcare setting in the period of 2002-2012. A combined pharmacoeconomic and epidemiological study was performed on the basis of the prevalence of hepatitis A infection in this 10-year period. The investments in the vaccination were considered as costs and the avoided costs in the case of vaccination of all one-year old children in the population - as benefits. The results show that the vaccination of one-year-old children would be cost effective to the healthcare system in the years with an epidemiologic outbreak, as in these years the total cost of treatment of patients with hepatitis A infection exceeds the cost for vaccination of the whole one-year-old cohort. The critical threshold is 4600 infected patients per year that equalize the benefits to costs. The inclusion of HAV vaccine in the National Immunization Calendar would be cost effective for the healthcare system when the vaccination is performed in certain risk groups and could help to decrease the circulation of the virus in the general population.