Quality of life and disease activity of patients with rheumatoid arthritis on tofacitinib and biologic disease-modifying antirheumatic drug therapies.

The aim of this study was to analyze the therapeutic results of rheumatoid arthritis (RA) therapy with different biologic disease-modifying antirheumatic drugs (bDMARDs) and the first Janus-activated kinase (JAK) inhibitor in real-life clinical settings. This is a prospective, observational, longitudinal study at the largest rheumatology clinic in Bulgaria conducted during the period 2012-2020. One hundred seventy-four patients were followed up for a period of one year. Patients naïve to biological therapy were consecutively assigned on the available at the time bDMARDs (infliximab, etanercept, adalimumab, rituximab, golimumab, cetrolizumab, tocilizumab) or tofacitinib. We evaluated the disease activity score (DAS28-CRP), Health assessment questionnaires (HAQ) and short form 36 (SF-36) were applied at the initiation of biological therapy, after 6, and 12 months of follow-up. We analyze the changes in the two major subgroups of SF36-physical (MCS) and mental health (PCS). The age and gender distribution were similar between the groups on bDMARDs and tsDMARD. All observed indicators for disease control and QoL improve after the initiation of the biological or JAK inhibitor therapy. We also analyze the effect of therapies on DAS28-CRP, HAQ, SF-36 (PCS, MCS). Dispersion analysis for the effect of therapy measured through DAS28 between 1st and 3rd measurement shows a statically significant difference in between the average effect of therapies (p = 0.005). According to the average change in DAS28 between the first and third measurement the most effective is the golimumab (Median difference = 2.745), followed by rituximab (median = 2.305) and etanercept (median = 2.070). According to the average change in HAQ between first and third the most effective is tofacitinib (median 0.563), followed rituximab and infliximab (median 0.500 for both). Less effective in term of HAQ changes between the first and third measurement appears to be etanercept (median difference 0.250). All differences are statistically significant (p < 0.05). Regarding the changes in the QoL measured with SF-36 MCS and PCS there is no statistically significant differences in the average effect of different therapeutic agents. Tofacitinib is non-inferior in comparison to bDMARDs and improve both-disease activity and QoL in patients with RA.

Development of transferability guidance for integrated care models with special focus on Central and Eastern European countries.

AIM: To develop pragmatic recommendations for Central and Eastern European (CEE) policymakers about transferability assessment of integrated care models established in higher income European Union (EU) countries. METHODS: Draft recommendations were developed based on Horizon 2020-funded SELFIE project deliverables related to 17 promising integrated care models for multimorbid patients throughout Europe, as well as on an online survey among CEE stakeholders on the relevance of implementation barriers. Draft recommendations were discussed at the SELFIE transferability workshop and finalized together with 22 experts from 12 CEE countries. RESULTS: Thirteen transferability recommendations are provided in three areas. Feasibility of local implementation covers the identification and prioritization of implementation barriers and proposals for potential solutions. Performance measurement of potentially transferable models focuses on the selection of models with proven benefits and assurance of performance monitoring. Transferability of financing methods for integrated care explores the relevance of financing methodologies and planning of adequate initial and long-term financing. CONCLUSIONS: Implementation of international integrated care models cannot be recommended without evidence on its local feasibility or scientifically sound and locally relevant performance assessment in the country of origin. However, if the original financing method is not transferable to the target region, development of a locally relevant alternative financing method can be considered.

Costs and outcomes for individuals with psychosis prior to hospital admission and following discharge in Bulgaria.

PURPOSE: To examine the cost of psychotic disorders in Bulgaria prior to hospital admission and following discharge from two perspectives: healthcare and societal; and to evaluate the association between the costs and the patient's characteristics. METHODS: 96 individuals with psychosis experiencing psychotic exacerbation and their primary caregivers were evaluated upon the patients' hospital admission. The participants were followed up after 12 months. The costs were evaluated from healthcare and societal perspective using the Client's Sociodemographic and Service Receipt Inventory (CSSRI-EU). The psychopathology, functioning, quality of life and caregiver's burden were measured using standardized instruments. The mean differences in the costs and the associations with the clinical and socio-demographic characteristics of the patients were evaluated. RESULTS: The healthcare costs increase from EUR 120.66 (SD = 163.85) at baseline to EUR 177.54 (SD = 136.98) at follow-up. The total cost from societal perspective are up to sixfold higher than the healthcare costs at both assessments [EUR 717.41 (SD = 402.33) and 880.40 (SD = 1592.00), respectively] and do not change significantly. A major shift in the subtypes of costs, and significant associations of the costs with the socio-demographic and clinical characteristics, were found. CONCLUSIONS: Psychotic disorders and psychotic exacerbations have high societal costs. The underfunding of mental healthcare in Bulgaria is at the expense of high caregivers' and societal cost. The treatment of psychotic exacerbation is effective and investment in mental healthcare for the improvement of the psychopathology, social functioning, quality of life and the burden of informal care should be viewed as a sustainable investment.

Аn affordability of statins therapy - comparative analysis between Ukraine and Bulgaria.

BACKGROUND: The statins are а developing group of cardiovascular medicines, widely used for dyslipidemia. As a whole statins consumption leads to reduction in cardiovascular events and death, and improves the disease control. The main study issue considers the differences in an affordability to lipid lowering medicines in the countries with the highest morbidity and mortally rate within and outside EU. The affordability has been researched by exploring the price differences and average wages. METHODS: On total 7 international nonproprietary names and 19 dosage forms available on both markets are observed during 2013-2016. An average, minimum, and maximum retail prices per DDD, standard deviation (SD) has been calculated for all marketed dosage forms. A price ratio between the minimal and maximal price per DDD is estimated in order to evaluate their difference. Affordability of the treatment is determined as the number of working hours per month needed for patient to purchase medicines for a monthly therapy. RESULTS: Large variations of price per DDD, SD and the average price exist between different dosage forms in both countries. The highest value of a price ratio is observed for 5 mg rosuvastatin in Bulgaria and 10 mg rosuvastatin in Ukraine. The number of working hours needed to cover monthly therapy has increased during 2013-2016 in Ukraine. The most affordable is treatment with a generic atorvastatin in Bulgaria and generic rosuvastatin in Ukraine. The most expensive rosuvastatin in Bulgaria and atorvastatin in Ukraine are found as the least affordable for a monthly therapy. CONCLUSIONS: The decrease of prices for statins is not the only reason influencing patients' affordability to therapy for statin therapy in Ukraine and Bulgaria. The difference in affordability in Ukraine and Bulgaria is affected mainly by the economic development in the country as well as wages variation.

EQ-5D studies in musculoskeletal and connective tissue diseases in eight Central and Eastern European countries: a systematic literature review and meta-analysis.

EQ-5D is becoming the preferred instrument to measure health-state utilities involved in health technology assessment. The objective of this study is to assess the state of EQ-5D research in musculoskeletal disorders in 8 Central and Eastern European countries and to provide a meta-analysis of EQ-5D index scores. Original research articles published in any language between Jan 2000 and Sept 2016 were included, if they reported any EQ-5D outcome from at least two musculoskeletal patients from Austria, Bulgaria, the Czech Republic, Hungary, Poland, Romania, Slovakia, or Slovenia. Risk of bias was assessed with the Cochrane Collaboration's tool. Twenty-nine articles (5992 patients) were included on rheumatoid arthritis (n = 7), osteoporosis (n = 5), chronic pain (n = 5), osteoarthritis (n = 4), ankylosing spondylitis (n = 2), psoriatic arthritis (n = 2), total hip replacement (n = 2), and scleroderma (n = 2). Low back pain was under-represented, while studies in neck pain, systemic lupus erythematosus, gout, and childhood disorders were lacking. EQ-5D index scores were reported in 24 studies, while the version of the instrument and the value-set was not specified in 41% and 46% of the articles, respectively. Meta-analysis was performed on 24 disease states involving 6876 observation points. Intervention effect was reported in 22 subgroups, out of which risk of bias was low in 41%. This review provides recommendations to improve reporting standards of EQ-5D results and highlights potential areas for future research. Coordinated research in conditions with greatest public health impact as well as a development of a regional value-set could provide locally relevant health-state utilities that are transferable among countries within the region.

EQ-5D in Central and Eastern Europe: 2000-2015.

OBJECTIVE: Cost per quality-adjusted life year data are required for reimbursement decisions in many Central and Eastern European (CEE) countries. EQ-5D is by far the most commonly used instrument to generate utility values in CEE. This study aims to systematically review the literature on EQ-5D from eight CEE countries. METHODS: An electronic database search was performed up to 1 July 2015 to identify original EQ-5D studies from the countries of interest. We analysed the use of EQ-5D with respect to clinical areas, methodological rigor, population norms and value sets. RESULTS: We identified 143 studies providing 152 country-specific results with a total sample size of 81,619: Austria (n = 11), Bulgaria (n = 6), Czech Republic (n = 18), Hungary (n = 47), Poland (n = 51), Romania (n = 2), Slovakia (n = 3) and Slovenia (n = 14). Cardiovascular (21 %), neurologic (17 %), musculoskeletal (15 %) and endocrine, nutritional and metabolic diseases (13 %) were the most frequently studied clinical areas. Overall, 112 (78 %) of the studies reported EQ VAS results and 86 (60 %) EQ-5D index scores, of which 27 (31 %) did not specify the applied tariff. Hungary, Poland and Slovenia have population norms. Poland and Slovenia also have a national value set. CONCLUSIONS: Increasing use of EQ-5D is observed throughout CEE. The spread of health technology assessment activities in countries seems to be reflected in the number of EQ-5D studies. However, improvement in informed use and methodological quality of reporting is needed. In jurisdictions where no national value set is available, in order to ensure comparability we recommend to apply the most frequently used UK tariff. Regional collaboration between CEE countries should be strengthened.

Health technology assessment in the Balkans: opportunities for a balanced drug assessment system.

Countries in the Balkan region use pharmaco-economic data for decisions about the inclusion of new pharmaceuticals into their positive drug lists, but no predefined frameworks are used and resources for health technology assessment (HTA) are limited. The goal of this analysis is to investigate into possible development directions for the HTA system in the region, and provide some practical recommendations for a sustainable model. For this purpose, the main factors currently influencing HTA in Balkan countries are briefly presented, and possible development strategies are compared. A resource-saving balanced assessment approach is proposed. It is aligned with available resources and capabilities, and helps access to new pharmaceuticals while ensuring the transparency of decision-making processes and the stability of the pharmaceutical budget.

ISO 9001 certification for hospitals in Bulgaria: does it help service?

The aim of our study is to review the published literature on establishment and implementation of ISO 9001 QMS in European hospitals, to study the availability of International Organization for Standardization (ISO) quality management systems (QMS) in Bulgarian hospitals and to outline the main advantages of ISO implementation in the hospitals in Bulgaria. The information on availability of ISO QMS in the hospitals in Bulgaria was gathered via Bulgarian certification register, the registries of various quality associations, websites of hospitals and certification companies presented in Bulgaria. A total number of 312 hospitals in Bulgaria were screened for the availability of QMS certified against the ISO 9001 requirements. The experience of European hospitals that implemented QMS is positive and the used approaches to improve the processes and the demonstrated effects from ISO implementation are analysed by the researchers. Unlike other European Union member states, the establishment of quality management systems in Bulgaria is not compulsory. However, our study revealed that 14.42% of the hospitals in Bulgaria have implemented and have certified quality systems against the requirements of ISO 9001. Our study confirmed that a quality management system using the ISO 9001 standard is useful for the hospitals as it can help to increase the operational efficiencies, to reduce errors, improve patient safety and produce a more preventive approach instead of a reactive environment.

Humanistic and economic aspects of haemophilia treatment in Bulgaria. Comparison between two therapeutic approaches: prophylactic vs. on-demand treatment.

The aim of the present study was to calculate the cost-effectiveness of on-demand and prophylactic treatments of severe haemophilia A for Bulgarian patients. The point of view is that of all patients suffering from severe haemophilia A. An epidemiological model was created, which includes data regarding the number of patients divided into age groups up to 74 years. In the model, the transition age from prophylactic to on-demand treatment was gradually increased to up to 40 years. Costs of blood clotting factor, hospitalization, major surgery and indirect costs were considered; incremental cost-effectiveness ratio was calculated. The results showed that despite the increase in the costs for factor VIII with 20 million BGN, the saving obtained from other health services and indirect expenses reduce the overall expenses with 5.3 million BGN. If there is a gradual increase in the age when patients are transferred from a prophylactic to an on-demand regimen, the costs for factor VIII would increase from 10.4 million to 19.7 million BGN, but due to a decrease in indirect costs as well as other health service costs, the total costs would decrease. The sensitivity analysis showed that the costs for clotting factor VIII are what influences the cost-effectiveness in both regimes. This indicates that decreases in the factor VIII cost will increase the overall efficiency in both regimes. In conclusion, the application of the prophylactic regime for patients up to 40 years of age will provide better treatment, increase the quality of life and decrease the incremental costs.

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.

Comparison of health-related quality-of-life measurement instruments in diabetic patients.

The objective of the study was to compare three different questionnaires (Short Form (SF)-6D, EuroQuol (EQ)-5D and WHO-5) to establish which one is more sensitive and which one gives an adequate assessment of the quality of life in patients with diabetes. In an observational and transversal study with duration of 4 months, in 5 Bulgarian cities, 146 patients were randomly selected. The following quality-of-life measuring instruments were applied: 146 questionnaires SF-6D, 146 questionnaires EQ-5D and 103 questionnaires of WHO-5. Descriptive statistics, chi-Square and correlation coefficients were used for data analysis. The study assessed the quality of life of patients suffering from diabetes mellitus with a mean age of 57.39 years (standard deviation (SD) 17.087); 95% confidence interval (CI) 54.60-60.19; 76% of the patients had diabetes type 2. The patients received a mean SF-6D score of 0.6290, an EQ-5D score of 0.6272, a visual analogue scale score of 0.7158 and a WHO-5 score of 0.4635. Preferences measured by the SF-6D and by the EQ-5D showed significant correlations with one another, and the Pearson coefficient was r = 0.906 (p < 0.01). The most current version of SF-6D, based on the 2002 model, was found to be valid and reliable when compared to the EQ-5D and is a questionnaire alternative to assess preferences in economic analysis carried out in health care.

The role of insurance policies in the drug pricing landscape.

INTRODUCTION: This overview paper aims at summarizing and analyzing the available literature on healthcare system organization and pricing policies of 11 European countries, comparing them to the Bulgarian pharmaceutical system. The countries were selected based on the reference basket for the pricing of pharmaceuticals in Bulgaria - Belgium, Greece, Spain, Italy, Latvia, Lithuania, Romania, Slovakia, Slovenia, and France. AREAS COVERED: In the first part, we explore the health system models in the above-mentioned countries. In the second part we explore the pricing and reimbursement policies, and in the third part we analyze healthcare and pharmaceutical economic indicators, as well as life expectancy. The major focus of the review is the outpatient care. EXPERT OPINION: In this work, we attempted to outline differences and similarities between the countries of interest. Despite the differences in their healthcare system organization, health and pharmaceutical expenditures constantly increased during the observed 2 decades. This increase in expenditures, however, has not had a significant impact on life-expectancy. Minor increases were observed - from 2 to 4 years total. No country had an expectancy above 85 years of age. It might be said that other factors are influencing the life expectancy to a greater extent.

Approved and Commercialized Antidiabetic Medicines (Excluding Insulin) in Seven European Countries-A Cross-Sectional Comparison.

Diabetes mellitus is a complex, multifactorial, progressive condition with a variety of approved therapeutic options. The purpose of this study was to offer an overview of the authorized antidiabetic medicines (excluding insulin) compared with marketed products in seven European countries. Data were obtained from primary sources, including the websites of national authorities and directly from specialists in the countries of interest. The range of marketed medicines compared with the authorized group was assessed in terms of active pharmaceutical ingredients (>60% in Bulgaria, France, Serbia), brand names (>70% in Bulgaria, the Czech Republic, Romania, Serbia, Spain), pharmaceutical forms (>60% in all countries), strengths (>60% in Bulgaria, the Czech Republic, Romania, Serbia, Spain), marketing authorization holder (≥50% in all countries) and the status of medicine. Spain was found to have the highest number of products based on most of these attributes. Over 90% of authorized medicines had a pharmacy price in Serbia. Regarding the newer class of GLP-1 receptor agonists, a retail price for all approved substances was available in Bulgaria, Romania, Serbia, and Spain. Only one brand name with one concentration was found available for some agents, being susceptible to drug shortages: glibenclamide (Romania, Serbia, Spain), glipizide (the Czech Republic, Poland, Romania, Spain), glisentide (Spain), acarbose (the Czech Republic), sitagliptin (Bulgaria, Poland), vildagliptin (the Czech Republic, Poland) and saxagliptin (the Czech Republic, France, Romania, Serbia). An overview of the national and international therapeutic options may allow competent authorities and health professionals to take rapid measures in case of supply problems or health crises.

Clinical aspects of reimbursement policies for orphan drugs in Central and Eastern European countries.

Objectives: The aim of this study was to characterize the reimbursement policy for orphan drugs (ODs) in Central and Eastern European (CEE) countries in relation to the availability and impact of clinical evidence, health technology assessment (HTA) procedure, selected economic indicators, and the drug type according to indications. Materials and methods: A list of authorized medicines with orphan designation and information about active substance, Anatomical Therapeutic Chemical (ATC) classification, and therapeutic area was extracted from the web-based register of the European Medicines Agency (EMA). A country-based questionnaire survey was performed between September 2021 and January 2022 in a group of selected experts from nine CEE countries (an invitation was sent to 11 countries). A descriptive and statistical analysis was conducted to determine statistical significance, correlations, between the drug or country characteristic and the positive recommendation or reimbursement of ODs. Results: The proportion of reimbursed orphan drugs differed between countries, ranging from 17.7% in Estonia to 49.6% in Hungary (p < 0.001). The odds that ODs were reimbursed were reduced in countries with a "strong" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), the presence of other additional specific clinical aspects (e.g., genomic data) considered in the reimbursement decision (p < 0.001) and mandatory (without exception) safety assessments (p=0.004). The probability that ODs were reimbursed was increased in countries with a "moderate" level of impact of drug safety and efficacy on reimbursement decisions (p=0.018), when reimbursement decisions are dependent on the EMA registration status and orphan drug designation (p < 0.001), the presence of the "positive HTA recommendation guarantees reimbursement" policy (p < 0.001), higher GDP per inhabitant (p=0.003), and higher healthcare expenditure (p < 0.001). Conclusion: We found that there are differences among CEE countries in the reimbursement of orphan drugs, and we identified aspects that may influence these differences. Safety, efficacy, and specific clinical aspect issues significantly influenced reimbursement decisions. Antineoplastic and immunomodulating agents drugs were the largest group of ODs and increased the chance of getting a positive recommendation. The higher GDP per inhabitant and healthcare expenditures per inhabitant were positively linked to the chance that an OD receives reimbursement.

Economic evaluation of continuous subcutaneous insulin infusion for children with diabetes - a pilot study: CSII application for children - economic evaluation.

BACKGROUND: The objective of this study is to assess the cost of using continuous subcutaneous insulin infusion to treat children with type-1diabetes in Bulgaria, considering changes in body mass index (BMI) and the glycated hemoglobin. The study was performed from the perspective of the Bulgarian National Health Insurance Fund (NHIF) and patients. METHODS: A total of 34 pediatric type-1-diabetes patients were observed for 7 months, divided into 2 groups - on pumps and on insulin analogue therapy. Patient demographic data, BMI and glycated hemoglobin level were obtained and recorded. The cost of insulin, pumps, and consumables were calculated and compared with changes in glycated hemoglobin level. The incremental cost-effectiveness ratio was below the threshold value of gross domestic product per capita. RESULTS: The results were sensitive to changes in glycated hemoglobin level. Improvements associated with glycemic control led to a reduced glycated hemoglobin level that could ensure good diabetes management, but its influence on BMI in growing children remains unclear. CONCLUSION: Continuous subcutaneous insulin infusion appears to be more cost-effective for the Bulgarian pediatric population and health care system.

Complex regional pain syndrome acceptance and the alternative denominations in the medical literature.

OBJECTIVE: To analyze the use of the term 'complex regional pain syndrome' in the medical literature and evaluate whether or not the traditional names 'reflex sympathetic dystrophy' and 'causalgia' have already been replaced with the new terms 'complex regional pain syndrome type I' and 'complex regional pain syndrome type II', respectively. MATERIALS AND METHODS: The Scopus and PubMed databases were searched for reports written between 2001 and 2012 for the following descriptors in the titles: 'complex regional pain syndrome', 'complex regional pain syndrome type I', 'complex regional pain syndrome type 1', 'complex regional pain syndrome type II', 'complex regional pain syndrome type 2', 'CRPS', 'CRPS type I', 'CRPS type 1', 'CRPS type II', 'CRPS type 2', 'reflex sympathetic dystrophy', 'algodystrophy', 'algoneurodystrophy', 'causalgia', 'transient osteoporosis', 'Sudeck', and 'shoulder-hand syndrome'. RESULTS: Systematization of the 1,318 articles found yielded the following: 953 (72.31%) articles for the descriptor 'complex regional pain syndrome' and a further 94 (7.13%) for its abbreviation 'CRPS'; 180 (13.66%) for 'reflex sympathetic dystrophy'; 33 (2.50%) for 'shoulder-hand syndrome'; 29 (2.20%) for 'algodystrophy'; 13 (0.99%) for 'causalgia'; 13 (0.99%) for 'Sudeck'; 2 (0.15%) for 'algoneurodystrophy', and 1 (0.08%) for 'transient osteoporosis'. The total number of articles using new terminology represents 1,047 (79.44%) of all articles. CONCLUSION: The new neutral term 'complex regional pain syndrome' was most commonly used and will likely replace the traditional names 'reflex sympathetic dystrophy' and 'causalgia'. The new terminology is now widely accepted by the medical professionals who are mostly engaged in the treatment of CRPS patients, but not yet so in other medical spheres.

Study of Symptom Severity and Adherence to Therapy of Myelofibrosis Patients Treated with Ruxolitinib.

We aimed to explore symptom severity and adherence to therapy for patients with myelofibrosis treated with ruxolitinib in Bulgaria. It is a prospective, non-interventional study performed at the specialized hospital for active treatment of hematological diseases in Sofia during 2022-2023. Date of diagnosis, demographic characteristics, clinical indicators, ruxolitinib dose, and other data points were collected. Clinical indicators were assessed at baseline, in the middle, and at the end of observation. Severity of symptoms was measured with MPN-SAF TSS and adherence to therapy with the Morisky 4 questionnaire six times during the observation. The mean age of diagnosis was 58.5 years, with the average duration of disease of 3 years. Patients' laboratory results were within physiological ranges, with spleen size experiencing a constant decrease. The average value for the severity of the symptoms per MPN-SAF TSS results decreased significantly, indicating better disease control. The average adherence to therapy did not change and remained high at around 9 points, except for one patient. In conclusion the treatment of myelofibrosis patients with ruxolitinib decreased symptom severity and spleen size. Patients were adherent to the therapy over the observed period, but as treatment duration increases, the risk of adherence decreases.

Tackling reimbursement challenges to fair access to medicines - introduction to the topic.

INTRODUCTION: Ensuring both financial and physical access to medicines is a challenge for the reimbursement system. How countries are currently tackling this challenge is an issue worth exploring in this review paper. AREAS COVERED: The review covered three areas of studies such as pricing, reimbursement, and patient access measures. We compared the use and shortcomings of all measures influencing patients' access to medicines. EXPERT OPINION: In this work, we tried attempted to outline fair access policies toward reimbursed medicines in a historical manner by researching the measures accepted during different time periods by governments that affect patient access. From the review, it is evident that the countries are following similar models with a focus on pricing measures, reimbursement measures, and measures directly affecting the patients. It is our opinion that most of the measures are focused on ensuring the sustainability of the payer's funds and less are those that stimulate faster access. Even worse, we found that studies that are measuring the real patients access, and affordability are scarce.

Therapeutic Results and Survival of Patients with Myelofibrosis Treated with Ruxolitinib-A Real-Life Longitudinal Study.

The aim of this study was to analyze the therapeutic results and survival of patients with myelofibrosis treated with ruxolitinib in comparison with a group on standard therapy. It is a cross-sectional, retrospective, non-interventional, real-life study that was performed between January 2000 and February 2023. Patients treated between 2000 and 2016, before the introduction of ruxolitinib, constituted the control group (n = 45), while those treated after May 2016, after ruxolitinib inclusion, constituted the active group (n = 66). Demographic characteristics, clinical indicators, the severity of the disease, and survival were explored using Kaplan-Meier survival analyses. Spearman's correlation, linear regression, and other statistical analyses were performed. According to the Kaplan-Meier analysis, there was a 75.33% reduction in the fatality risk in the sample. On a general-population level, the fatality risk in the group treated with ruxolitinib varied between 7.9% and 77.18% compared to that of the risk in the control group. There was a decrease in blood parameters (leukocytes, hemoglobin, and platelets) and spleen size. During the first six months, the spleen size of the patients on ruxolitinib decreased by 6%, and during the second six months, it decreased by another 9%. This study shows that patients in a real-life clinical setting treated with ruxolitinib exhibited improved clinical signs of the disease, had a lower symptom severity, and survived longer than patients on standard therapy before ruxolitinib's entrance into the national market. The improvements correlate with those reported in randomized clinical trials.

How Managed Entry Agreements Influence the Patients' Affordability to Biological Medicines-Bulgarian Example.

Managed entry agreements are applied in almost all European countries in order to improve patients' access to therapy. The current study aims to evaluate the changes in the affordability of biological medicines for patients in Bulgaria during 2019-2022. The study is a top-down macroeconomic analysis of the key economic indicators and reimbursed costs of biologic therapies. Affordability was determined as the number of working hours needed to pay for monthly therapy. The average NHIF budget for pharmaceuticals increased significantly along with inflation in the healthcare sector. Bulgarian patients had to devote a large part of their income to buying medicines if a co-payment existed. The percentage of the monthly income of pensioners needed for therapy co-payment varied between 10% and 280%. The hours of work required to purchase a package of biologicals varied between 7 and 137 working hours. The global economic crisis has affected Bulgaria and led to worsening economic parameters. There are still no well-established practices to control public spending, as the measures taken to reduce the final cost of medicines mainly affect the pharmaceutical companies. This type of cost-containment policy provides an opportunity for innovative treatment with biologicals for patients with inflammatory diseases. Most of the therapies cost more than the patients' monthly income.