PP016—Exposure to antipsychotics with pro-arrhythmic risk: Combining adverse drug reactions with drug utilization data

e22 Volume 35 Number 8S Department of Clinical Pharmacology, and Department of Dentistry, Oral and Maxillofacial Surgery; Department of Clinical Pharmacology; and Department of Dentistry, Oral and Maxillofacial Surgery, Jichi Medical University, Shimotsukeshi, Japan Introduction: Docetaxel, cisplatin plus 5-FU (DCF) regimen is a useful chemotherapy against malignant diseases such as advanced head and neck cancer. However, DCF regimen is sometimes withdrawn by severe myelosuppression and nonhematologic toxic effects, including mucositis. Previous animal and clinical studies showed that the degrees of docetaxel-, cisplatin-, and 5-FU–induced toxicities depend on their dosing time. We have reported that the frequency of docetaxel-induced intestinal mucositis was greater after dosing at an active phase than at an inactive phase in mice. The aim of the present study was to determine the influence of dosing schedule of DCF regimen on chemotherapy-induced toxicities in clinical practice. Patients (or Materials) and Methods: Patients with oral squamous cell carcinoma treated with DCF regimen were randomly allocated to the following 2 groups: chemotherapy started from morning (10:30) in the first group and evening (18:30) in the second group. Hematologic and nonhematologic adverse effects were assessed for 14 days after the start of chemotherapy. Results: The most frequently observed mild to severe adverse effects were neutropenia, diarrhea, stomatitis, and nausea. The frequency of grade 3 to 4 neutropenia was 62.5% (5 of 8) in the morning group and 28.6% (2 of 7) in the evening group. Grade 3 to 4 event of stomatitis and grade 3 event of nausea were more detected in the morning group. Conclusion: These findings suggest that chronotherapy of DCF regimen might diminish severe adverse effects in patients with oral squamous cell carcinoma. Disclosure of Interest: None declared

Introduction and utilization of high priced HCV medicines across Europe; implications for the future

Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. de Bruijn et al. HCV Medicines Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance

Introduction and utilization of high priced HCV medicines across Europe : implications for the future

Background: Infection with the Hepatitis C Virus (HCV) is a widespread transmittable disease with a diagnosed prevalence of 2.0%. Fortunately, it is now curable in most patients. Sales of medicines to treat HCV infection grew 2.7% per year between 2004 and 2011, enhanced by the launch of the protease inhibitors (PIs) boceprevir (BCV) and telaprevir (TVR) in addition to ribavirin and pegylated interferon (pegIFN). Costs will continue to rise with new treatments including sofosbuvir, which now include interferon free regimens. Objective: Assess the uptake of BCV and TVR across Europe from a health authority perspective to offer future guidance on dealing with new high cost medicines. Methods: Cross-sectional descriptive study of medicines to treat HCV (pegIFN, ribavirin, BCV and TVR) among European countries from 2008 to 2013. Utilization measured in defined daily doses (DDDs)/1000 patients/quarter (DIQs) and expenditure in Euros/DDD. Health authority activities to influence treatments categorized using the 4E methodology (Education, Engineering, Economics and Enforcement). Results: Similar uptake of BCV and TVR among European countries and regions, ranging from 0.5 DIQ in Denmark, Netherlands and Slovenia to 1.5 DIQ in Tayside and Catalonia in 2013. However, different utilization of the new PIs vs. ribavirin indicates differences in dual vs. triple therapy, which is down to factors including physician preference and genotypes. Reimbursed prices for BCV and TVR were comparable across countries. Conclusion: There was reasonable consistency in the utilization of BCV and TVR among European countries in comparison with other high priced medicines. This may reflect the social demand to limit the transmission of HCV. However, the situation is changing with new curative medicines for HCV genotype 1 (GT1) with potentially an appreciable budget impact. These concerns have resulted in different prices across countries, with their impact on budgets and patient outcomes monitored in the future to provide additional guidance

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growing prevalence of both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimise the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need

Use of drugs against osteoporosis in the Baltic countries during 2010–2014

Background and objective Osteoporosis is a major health threat nowadays. Aging of the population and changes in peoples’ lifestyle result in a constant increase in the number of fractures all over the world. Our study aimed at describing the drug utilization pattern and choice of active substances of antiosteoporotic medicines in the Baltic countries. Materials and methods Sales data of the antiosteoporotic medicines was obtained from the internet. These are available on the website of medicines regulatory agencies. The World Health Organization (WHO) methodology of Anatomical Therapeutic Chemical (ATC) classification and defined daily dose (DDD) was used to compare the data among countries. Results During the study period the consumption of antiosteoporotic medicines was rather stable in all the countries. The overall choice of active substances used to treat osteoporosis is similar in all the Baltic countries but the market shares of substances were different. Estonia stands out with high use of combination product of alendronic acid and colecalciferol. In Latvia the highest consumption was of risedronic acid. In Lithuania the most used active substance in 2014 was ibandronic acid and second was denosumab with 0.8 daily doses per 1000 inhabitants per day (DID) and 25% of the total share. Conclusions The differences in consumption of drugs against osteoporosis in the Baltic countries are not very big. The consumption of antiosteoporotic drugs is not to be regarded as sufficient though. The generally low consumption of osteoporotic medicines in the Baltic countries can be attributed to the overall less than EU average wealth of the countries and less than optimal expenditure on healthcare out of the GDP

Use of a national database as a tool to identify primary medication non-adherence: The Estonian ePrescription system

Background Medication adherence can be divided into primary and secondary adherence. Primary medication non-adherence (PMN) occurs when a patient does not obtain medicine with their initial prescription. Secondary non-adherence measures prescription refills among patients who previously filled their first prescription. While secondary non-adherence has been studied thoroughly, PMN has been assessed less extensively, due to lack of available data. Estonian ePrescription system might prove a valuable tool for this. Objectives The aim of this study was to evaluate PMN and the interval between prescribing and dispensing of medicines using the Estonian ePrescriptions database to establish its potential use for this purpose and for other qualitative drug utilization research measures. Osteoporosis medicines were used as an example. Methods The Estonian Prescription Centre was used to evaluate if patients purchase medicines after initial prescription of osteoporosis medicine. Prescriptions from 2012 to 2015 of all patients over 18 were included. PMN was defined as the first prescription not being dispensed before it expired (60 days). The rate of PMN was calculated. Results Estonian ePrescription System enabled fast evaluation of PMN of osteoporosis patients based on data about prescribing, dispensing and time intervals in-between. Of patients who started osteoporosis treatment 13.1% were primary non-adherent. Of primary non-adherent patients 42% still started treatment at some point during the study. Of patients who did purchase their first prescription 80.4% did so within a week and 95% within 25 days. Conclusion The Estonian ePrescription system is a useful tool for monitoring PMN. The PMN of osteoporosis medicines was identified as lower than previously reported. More similar type of studies about other groups of medicines would be needed to understand the pattern of PMN and give valuable information to healthcare specialists about how to increase initiation of treatment

Potential osteoporosis MRNA biomarkers discovered in transcriptome study of Estonian postmenopausal female patients

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Featured Article: Transcriptional landscape analysis identifies differently expressed genes involved in follicle-stimulating hormone induced postmenopausal osteoporosis

Osteoporosis is a disorder associated with bone tissue reorganization, bone mass, and mineral density. Osteoporosis can severely affect postmenopausal women, causing bone fragility and osteoporotic fractures. The aim of the current study was to compare blood mRNA profiles of postmenopausal women with and without osteoporosis, with the aim of finding different gene expressions and thus targets for future osteoporosis biomarker studies. Our study consisted of transcriptome analysis of whole blood serum from 12 elderly female osteoporotic patients and 12 non-osteoporotic elderly female controls. The transcriptome analysis was performed with RNA sequencing technology. For data analysis, the edgeR package of R Bioconductor was used. Two hundred and fourteen genes were expressed differently in osteoporotic compared with non-osteoporotic patients. Statistical analysis revealed 20 differently expressed genes with a false discovery rate of less than 1.47 × 10−4 among osteoporotic patients. The expression of 10 genes were up-regulated and 10 down-regulated. Further statistical analysis identified a potential osteoporosis mRNA biomarker pattern consisting of six genes: CACNA1G, ALG13, SBK1, GGT7, MBNL3, and RIOK3. Functional ingenuity pathway analysis identified the strongest candidate genes with regard to potential involvement in a follicle-stimulating hormone activated network of increased osteoclast activity and hypogonadal bone loss. The differentially expressed genes identified in this study may contribute to future research of postmenopausal osteoporosis blood biomarkers