Adoption of biosimilar infliximab for rheumatoid arthritis, ankylosing spondylitis, and inflammatory bowel diseases in the EU5: A budget impact analysis using a Delphi panel

Introduction: Introducing biosimilar infliximab for the treatment in rheumatology (rheumatoid arthritis and ankylosing spondylitis) and inflammatory bowel disease (Crohn's disease and ulcerative colitis) may reduce treatment costs associated with biologics. This study aimed to investigate the budget impact of adopting biosimilar infliximab in five European countries, considering that the budget impact includes the adoption of biosimilar infliximab and the availability of biologic alternatives such as vedolizumab, biosimilar etanercept, biosimilar rituximab, and other relevant factors. Methods: An existing budget impact model was adapted to forecast the budget impact in the UK, Germany, France, Spain, and Italy. Epidemiological parameters were derived from published literature reviewed in July 2015. Current market shares of biologics were derived from Therapy Watch (2012/2013 data). Respondents in a Delphi panel, conducted in 2015 and consisting of several leading rheumatologists and gastroenterologists from different nationalities, were asked to forecast uptake of biosimilar infliximab and estimate the proportion of patients eligible for a particular type of biological treatment, including biosimilar infliximab. Scenario analyses assessed the influence of various factors, including price reductions, on the budget. Results: Uptake of biosimilar infliximab was particularly expected for naïve patients; switching patients that already received other biologics was not expected much. Market shares after 5 years of biosimilar infliximab were ~2% in rheumatology in all five countries and in gastroenterology ranged from 4% in France to over 30% in Italy. Except for France, budgets were expected to decrease for rheumatologic diseases. For gastroenterology, budgets were expected to decrease in Spain and Italy. Budgets were expected to increase substantially in the UK and Germany, due to the introduction of vedolizumab in the studied period. In France, budget was expected to slightly increase for ankylosing spondylitis, Crohn's Disease, and ulcerative collitis. Savings in budget were expected in all countries, for all diseases, when larger price discounts on biosimilar infliximab were used. Discussion and Conclusion: This study has shown that only when price reductions are large en

Pharmacoeconomics of cardiovascular disease prevention

In this thesis, some of the methodological challenges in simulating and synthesizing pharmacoeconomic evidence in cardiovascular disease (CVD) prevention were assessed and potential solutions to those challenges were proposed. This includes a set of recommendations for enhancing the robustness of pharmacoeconomic analyses that apply CVD risk prediction models. The application of these recommendations was also explored in a simplified model of primary CVD prevention with antihypertensives. Another challenging issue relates to the robustness of evidence on the health-related quality of life (HRQoL) values used in pharmacoeconomic analyses. Here, evidence-synthesis was suggested as a relevant approach to, where appropriate, synthesize HRQoL values in specific CVD disorders as well as to indicate the level of heterogeneity across those values and possibly its sources. As an example, evidence-synthesis of instrument-specific HRQoL values in coronary heart disease and its underlying disease-forms was explored. In this study large heterogeneity within and between the instrument-specific values and inherent uncertainty if applied within pharmacoeconomic analysis, were found.This thesis also derives pharmacoeconomic evidence on the use of oral anticoagulants (i.e. vitamin K antagonists (VKAs) and novel oral anticoagulants (NOACs) e.g. apixaban, dabigatran) for secondary CVD prevention that may have direct societal relevance and implications in the Dutch setting. Firstly, optimizing the standard anticoagulant care with VKAs was explored. Secondly, the health and economic consequences associated with the use of apixaban for the prevention of stroke in non-valvular atrial fibrillation, and dabigatran for treatment and prevention of venous thromboembolism indicated that both apixaban and dabigatran were favourable alternatives to treatment with VKAs.In conclusion, several studies in this thesis emphasize that standardizing methodological requirements and recommendations for conducting and reporting pharmacoeconomic studies in CVD prevention including the ones proposed in this thesis may enhance the quality and validity of pharmacoeconomic evidence and reduce possible bias. Furthermore, this thesis provides pharmacoeconomic evidence that NOACs may present a valuable alternative to VKAs for thromboprophylaxis in the Dutch setting

Pharmacoeconomics of cardiovascular disease prevention

In this thesis, some of the methodological challenges in simulating and synthesizing pharmacoeconomic evidence in cardiovascular disease (CVD) prevention were assessed and potential solutions to those challenges were proposed. This includes a set of recommendations for enhancing the robustness of pharmacoeconomic analyses that apply CVD risk prediction models. The application of these recommendations was also explored in a simplified model of primary CVD prevention with antihypertensives. Another challenging issue relates to the robustness of evidence on the health-related quality of life (HRQoL) values used in pharmacoeconomic analyses. Here, evidence-synthesis was suggested as a relevant approach to, where appropriate, synthesize HRQoL values in specific CVD disorders as well as to indicate the level of heterogeneity across those values and possibly its sources. As an example, evidence-synthesis of instrument-specific HRQoL values in coronary heart disease and its underlying disease-forms was explored. In this study large heterogeneity within and between the instrument-specific values and inherent uncertainty if applied within pharmacoeconomic analysis, were found.This thesis also derives pharmacoeconomic evidence on the use of oral anticoagulants (i.e. vitamin K antagonists (VKAs) and novel oral anticoagulants (NOACs) e.g. apixaban, dabigatran) for secondary CVD prevention that may have direct societal relevance and implications in the Dutch setting. Firstly, optimizing the standard anticoagulant care with VKAs was explored. Secondly, the health and economic consequences associated with the use of apixaban for the prevention of stroke in non-valvular atrial fibrillation, and dabigatran for treatment and prevention of venous thromboembolism indicated that both apixaban and dabigatran were favourable alternatives to treatment with VKAs.In conclusion, several studies in this thesis emphasize that standardizing methodological requirements and recommendations for conducting and reporting pharmacoeconomic studies in CVD prevention including the ones proposed in this thesis may enhance the quality and validity of pharmacoeconomic evidence and reduce possible bias. Furthermore, this thesis provides pharmacoeconomic evidence that NOACs may present a valuable alternative to VKAs for thromboprophylaxis in the Dutch setting

Apigenin-7-O-glucoside versus apigenin

Bioactive potential of apigenin derivative apigenin-7-O-glucoside related to its antifungal activity on Candida spp. and cytotoxic effect on colon cancer cells was studied and compared with bioactive potential of apigenin. Antifungal activity was tested on 14 different isolates of Candida spp. using membrane permeability assay, measuring inhibition of reactive oxidative species and inhibition of CYP51 C. albicans enzyme. Cytotoxic potential of apigenin-7-O-glucoside was tested on colon cancer HCT116 cells by measuring cell viability, apoptosis rate and apoptosis- and colon cancer-related gene expression. Obtained results indicated considerable antifungal activity of apigenin-7-O-glucoside towards all Candida isolates. Breakdown of C. albicans plasma membrane was achieved upon treatment with apigenin-7-O-glucoside for shorter period of time then with apigenin. Reduction of intra- and extracellular reactive oxidative species was achieved with minimum inhibitory concentrations of both compounds, suggesting that reactive oxidative species inhibition could be a mechanism of antifungal action. None of the compounds exhibited binding affinity to C. albicans CYP51 protein. Besides, apigenin-7-O-glucoside was more effective compared to apigenin in reduction of cell’s viability and induction of cell death of HCT116 cells. Treatment with both compounds resulted in chromatin condensation, apoptotic bodies formation and apoptotic genes expression in HCT116 cells, but the apigenin-7-O-glucoside required a lower concentration to achieve the same effect. Compounds apigenin-7-O-glucoside and apigenin displayed prominent antifungal potential and cytotoxic effect on HCT116 cells. However, our results showed that apigenin-7-O-glucoside has more potent activity compared to apigenin in all assays that we used

Application of nonvascular interventional radiology procedures in the treatment of iatrogenic ureteral injuries

Introduction. He most common ureteral injuries are iatrogenic injuries. Diagnosis of ureteral lesions includes ultrasound, computer tomography, intravenous urography, anterograde and retrograde ureterography. For a definitive diagnosis it is necessary to determine the existence of the extralumination of contrast media from the ureter. Minor ureteral injuries can be treated with nonvascular interventional radiology procedures. Case presentation. We have presented two patients with iatrogenic ureteral in-juries. Injury in the first patient occurred at the sigmoid colon resection and partial resection of the bladder, whereas in the second patient the lesion was formed as a result of cesarean section. In both patients, there was a history of previously conducted interventions, clinical picture included fever and pain, a diagnosis was made by intravenous and anterograde urography. Patients were treated with interventional radiology procedures and they have been definitely cured. Conclusion. Methods of nonvascular inter-ventional radiology can be successfully applied in the treatment of minor iatrogenic ureteral injuries

Compliance and approach to voluntary HIV testing in a high-risk region for HIV transmission in Europe

Background: The Kosovo province is being considered as a high-risk region for the spread of HIV. Objective: To estimate the prevalence and factors associated with HIV testing in a sample of university students from the Serbian northern Kosovo province. Material and Methods: A questionnaire examining socio-demographic characteristics, HIV–related knowledge, attitudes towards people living with HIV (PLHIV) and HIV testing was used in data collection. A total of 1,017 students from the University of Priština temporarily seated in Kosovska Mitrovica completed the questionnaire. Results: Only 5.4% of students have previously been tested for HIV, even though the majority (70.9%) had a positive approach to HIV testing. Factors associated with having been tested for HIV were being male and younger, having interest in HIV testing and having previous contact with PLHIV. Being more knowledgeable about HIV and having stronger positive attitude towards PLHIV, being older, receiving information about HIV through friends and special educational programs, using condom at last sexual intercourse, having positive opinion on gays/lesbians and previous contact with PLHIV were associated with positive approach to HIV testing. Conclusion: Having a positive approach to HIV testing does not suggest that students would take the HIV test. However, students who have low HIV-related knowledge, negative approach or lack of interest in HIV testing (believing that there is no need to take it) would likely never take the HIV test. Increasing HIV-related knowledge, acceptance of PLHIV and access to testing facilities should be public health priorities to raise HIV testing rates. Keywords: HIV testing; attitude; knowledge; University students

Economic evaluation of apixaban for the prevention of stroke in non-valvular atrial fibrillation in the Netherlands

BACKGROUND: Stroke prevention is the main goal of treating patients with atrial fibrillation (AF). Vitamin-K antagonists (VKAs) present an effective treatment in stroke prevention, however, the risk of bleeding and the requirement for regular coagulation monitoring are limiting their use. Apixaban is a novel oral anticoagulant associated with significantly lower hazard rates for stroke, major bleedings and treatment discontinuations, compared to VKAs.OBJECTIVE: To estimate the cost-effectiveness of apixaban compared to VKAs in non-valvular AF patients in the Netherlands.METHODS: Previously published lifetime Markov model using efficacy data from the ARISTOTLE and the AVERROES trial was modified to reflect the use of oral anticoagulants in the Netherlands. Dutch specific costs, baseline population stroke risk and coagulation monitoring levels were incorporated. Univariate, probabilistic sensitivity and scenario analyses on the impact of different coagulation monitoring levels were performed on the incremental cost-effectiveness ratio (ICER).RESULTS: Treatment with apixaban compared to VKAs resulted in an ICER of €10,576 per quality adjusted life year (QALY). Those findings correspond with lower number of strokes and bleedings associated with the use of apixaban compared to VKAs. Univariate sensitivity analyses revealed model sensitivity to the absolute stroke risk with apixaban and treatment discontinuations risks with apixaban and VKAs. The probability that apixaban is cost-effective at a willingness-to-pay threshold of €20,000/QALY was 68%. Results of the scenario analyses on the impact of different coagulation monitoring levels were quite robust.CONCLUSIONS: In patients with non-valvular AF, apixaban is likely to be a cost-effective alternative to VKAs in the Netherlands.</p