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.

Adaptive Pathways: Possible Next Steps for Payers in Preparation for Their Potential Implementation.

Medicines receiving a conditional marketing authorization through Medicines Adaptive Pathways to Patients (MAPPs) will be a challenge for payers. The "introduction" of MAPPs is already seen by the European Medicines Agency (EMA) as a fait accompli, with payers not consulted or involved. However, once medicines are approved through MAPPs, they will be evaluated for funding by payers through different activities. These include Health Technology Assessment (HTA) with often immature clinical data and high uncertainty, financial considerations, and negotiations through different types of agreements, which can require monitoring post launch. Payers have experience with new medicines approved through conditional approval, and the fact that MAPPs present additional challenges is a concern from their perspective. There may be some activities where payers can collaborate. The final decisions on whether to reimburse a new medicine via MAPPs will have more variation than for medicines licensed via conventional processes. This is due not only to increasing uncertainty associated with medicines authorized through MAPPs but also differences in legal frameworks between member states. Moreover, if the financial and side-effect burden from the period of conditional approval until granting full marketing authorization is shifted to the post-authorization phase, payers may have to bear such burdens. Collection of robust data during routine clinical use is challenging along with high prices for new medicines during data collection. This paper presents the concept of MAPPs and possible challenges. Concerns and potential ways forward are discussed and a number of recommendations are presented from the perspective of payers.

Pricing and Reimbursement of Biosimilars in Central and Eastern European Countries.

Objectives: The aim of this study was to review the requirements for the reimbursement of biosimilars and to compare the reimbursement status, market share, and reimbursement costs of biosimilars in selected Central and Eastern European (CEE) countries. Methods: A questionnaire-based survey was conducted between November 2016 and January 2017 among experts from the following CEE countries: Bulgaria, Czech Republic, Croatia, Estonia, Hungary, Latvia, Lithuania, Poland, Slovakia, and Romania. The requirements for the pricing and reimbursement of biosimilars were reviewed for each country. Data on the extent of reimbursement of biologic drugs (separately for original products and biosimilars) in the years 2014 and 2015 were also collected for each country, along with data on the total pharmaceutical and total public health care budgets. Results: Our survey revealed that no specific criteria were applied for the pricing and reimbursement of biosimilars in the selected CEE countries; the price of biosimilars was usually reduced compared with original drugs and specific price discounts were common. Substitution and interchangeability were generally allowed, although in most countries they were at the discretion of the physician after a clinical assessment. Original biologic drugs and the corresponding biosimilars were usually in the same homogeneous group, and internal reference pricing was usually employed. The reimbursement rate of biosimilars in the majority of the countries was the same and amounted to 100%. Generally, the higher shares of expenditures were shown for the reimbursement of original drugs than for biosimilars, except for filgrastim, somatropin, and epoetin (alfa and zeta). The shares of expenditures on the reimbursement of biosimilar products ranged from 8.0% in Estonia in 2014 to 32.4% in Lithuania in 2015, and generally increased in 2015. The share of expenditures on reimbursement of biosimilars in the total pharmaceutical budget differed between the countries, with the highest observed value for Slovakia and Hungary and the lowest-for Croatia. Conclusions: The requirements for the pricing and reimbursement of biosimilar products as well as the access of patients to biologic treatment do not differ significantly between the considered CEE countries. Biosimilar drugs significantly influence the reimbursement systems of these countries, and the expenditure on the reimbursement of biosimilars is increasing as they are becoming more accessible to patients.

Hypertension and common complications --analysis of the ambulatory treatment cost.

AIM: Retrospective analysis of the prescribing practice and cost of ambulatory treatment of hypertension and its common complications--heart failure, sequelae of cerebrovascular disease, and angina pectoris. METHODS: Analysis of 3,240 reimbursable ambulatory prescriptions for hypertension, heart failure, sequelae of cerebrovascular disease and angina pectoris according to the complexity of the therapy and frequency of the prescribed medicines. Modeling and calculation of the expected monthly cost for outpatient therapy by using the "decision tree model". Sensitivity analysis is performed within the +/- 30% interval. RESULTS: 65% of the prescription were for the hypertension, and 35% for the observed complications. 1,297 prescriptions for hypertension include one medicine, 647 include two medicines, and only 8% of prescriptions were for three medicines. ACE inhibitors have been prescribed in 41% of all hypertension prescriptions, followed by beta-blockers (19%), Ca channel blockers (16%), diuretics (15%) etc. The prescriptions for hypertension complications are more diverse as therapeutic groups. The expected monthly cost of prescribed medicines per patient with hypertension alone is 6.90 Euro and in case of complications it is 10.71 Euro according to the prevalence of the complexity of therapy, and weighted monthly cost of medicines. The overall ambulatory cost is expected to be around 148 million Euro per year for near 1.5 million patients with 44% reimbursement. The cost of the therapy is sensitive more to changes in the medicine's prices than to its complexity. CONCLUSION: This study is a first step in providing information for evidence-based cost containment measures or policy decisions at ambulatory level in Bulgaria and for the assessment of the share of complications' therapy on the overall hypertension cost.

Safety assessment of newly marketed herbal medicines--methodological approach (Ginkgo biloba example in Bulgaria).

This study presents a proposal for the methodological approach for postmarketing safety profile assessment based on sales data and information for adverse drug reactions of newly introduced herbal medicinal products in the market. The study covers all herbal medicinal products containing dry extract of Ginkgo biloba leaves allowed for sale in Bulgaria. The methodological approach we create should be used for the establishment of the national herbal drugs policy complying with the recent European regulatory changes and specificity of the therapeutic practice in the country.

Prescribing patterns analysis in Bulgaria.

This study was developed to assess the prescribing patterns in the reimbursable and non-reimbursable prescriptions during 1996-2000 and their relevance to morbidity patterns in Bulgaria. It was manually collected 2266 reimbursable and 2330 non-reimbursable prescriptions with 4132 and 4291 prescribed drugs, respectively. The results shows that the leading causes for morbidity during 1995-99 were respiratory tract diseases with 40% relative share, followed by nervous system diseases with 12% share, cardiovascular diseases 10% share, digestive tract diseases, genito-urinary, skin and subcutaneous tissue diseases. All mentioned groups of diseases together with injuries and poisoning perform 70% of the total morbidity of the population. The prevailing causes for the mortality of the population were found to be cardiovascular, respiratory tract diseases, injuries and poisoning. The analysis of the collected prescriptions evaluated as mot often prescribed cardiovascular drugs (35%), drugs acting on digestive system (18%), nervous system (12%), respiratory system (11%) and anti-infective drugs (10%). In spite of the relevance among the prescribing and morbidity a lot of other factors are considered to be important as reimbursement system, pricing, and legislation.