Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

doi:10.3389/fphar.2016.00197

. 2016 Jul 22:7:197.

doi: 10.3389/fphar.2016.00197. eCollection 2016.

Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

Winnie de Bruijn¹, Cristina Ibáñez², Pia Frisk³, Hanne Bak Pedersen⁴, Ali Alkan⁵, Patricia Vella Bonanno⁶, Ljiljana S Brkičić⁷, Anna Bucsics⁸, Guillaume Dedet⁹, Jaran Eriksen¹⁰, Joseph O Fadare¹¹, Jurij Fürst¹², Gisselle Gallego¹³, Isabella P Godói¹⁴, Augusto A Guerra Júnior¹⁴, Hakkı Gürsöz⁵, Saira Jan¹⁵, Jan Jones¹⁶, Roberta Joppi¹⁷, Saim Kerman⁵, Ott Laius¹⁸, Newman Madzikwa¹⁹, Einar Magnússon²⁰, Mojca Maticic²¹, Vanda Markovic-Pekovic²², Amos Massele²³, Olayinka Ogunleye²⁴, Aisling O'Leary²⁵, Jutta Piessnegger²⁶, Catherine Sermet²⁷, Steven Simoens²⁸, Celda Tiroyakgosi²⁹, Ilse Truter³⁰, Magnus Thyberg³¹, Kristina Tomekova³², Magdalena Wladysiuk³³, Sotiris Vandoros³⁴, Elif H Vural⁵, Corinne Zara², Brian Godman³⁵

Affiliations

¹ Department of Pharmaceutical Sciences, Utrecht University Utrecht, Netherlands.
² Catalan Health Service - Servei Català de la Salut Barcelona, Spain.
³ Public Health Services Committee, Stockholm County Council Stockholm, Sweden.
⁴ Health Technologies and Pharmaceuticals, Division of Health Systems and Public Health, WHO Regional Office for Europe Copenhagen, Denmark.
⁵ Turkish Medicines and Medical Devices Agency, Ministry of Health Ankara, Turkey.
⁶ Independent Pharmaceutical Consultant Mellieha, Malta.
⁷ Croatian Health Insurance Fund Zagreb, Croatia.
⁸ Department of Finance, University of Vienna Vienna, Austria.
⁹ Ministry of Health Paris, France.
¹⁰ Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge Stockholm, Sweden.
¹¹ Department of Pharmacology, Ekiti State University Ado-Ekiti, Nigeria.
¹² Health Insurance Institute Ljubljana, Slovenia.
¹³ School of Medicine, The University of Notre Dame AustraliaDarlinghurst, NSW, Australia; Department of Pharmacology and Clinical Neuroscience, Umea UniversityUmea, Sweden.
¹⁴ School of Pharmacy, Graduate Program in Medicines and Pharmaceutical Assistance, Federal University of Minas GeraisBelo Horizonte, Brazil; Department of Social Pharmacy, SUS Collaborating Centre - Health Technology Assessment and Excellence in Health, College of Pharmacy, Federal University of Minas GeraisBelo Horizonte, Brazil.
¹⁵ Clinical Pharmacy, Rutgers State University of New JerseyPiscataway, NJ, USA; Horizon Blue Cross Blue Shield of New JerseyNewark, NJ, USA.
¹⁶ Scottish Medicines Consortium Glasgow, UK.
¹⁷ Pharmaceutical Drug Department, Azienda Sanitaria Locale of Verona Verona, Italy.
¹⁸ State Agency of Medicines Tartu, Estonia.
¹⁹ Ministry of Health and Child Care Harrare, Zimbabwe.
²⁰ Department of Health Services, Ministry of Health Reykjavík, Iceland.
²¹ Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana Ljubljana, Slovenia.
²² Faculty of Medicine, University of Banja LukaBanja Luka, Bosnia and Herzegovina; Ministry of Health and Social WelfareBanja Luka, Bosnia and Herzegovina.
²³ Department of Clinical Pharmacology, School of Medicine, University of Botswana Gaborone, Botswana.
²⁴ Clinical Pharmacology Unit, Department of Medicine, Lagos State University Teaching HospitalLagos, Nigeria; Department of Pharmacology and Therapeutics, Lagos State University College of MedicineLagos, Nigeria.
²⁵ National Centre for Pharmacoeconomics Dublin, Ireland.
²⁶ Hauptverband der Österreichischen Sozialversicherungsträger Wien, Austria.
²⁷ IRDES Paris, France.
²⁸ Department of Pharmaceutical and Pharmacological Sciences, KU Leuven Leuven, Belgium.
²⁹ Ministry of Health, Nelson Mandela Drive Gaborone, Botswana.
³⁰ Drug Utilisation Research Unit, Faculty of Health Sciences, Nelson Mandela Metropolitan University Port Elizabeth, South Africa.
³¹ Stockholms Läns Landsting, Hälso-och Sjukvårdsförvaltningen Stockholm, Sweden.
³² Faculty of Management, Comenius University Bratislava, Slovakia.
³³ HTA Consulting Cracow, Poland.
³⁴ School of Management and Business, King's College London London, UK.
³⁵ Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital HuddingeStockholm, Sweden; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of StrathclydeGlasgow, UK.

PMID: 27516740
PMCID: PMC4964878
DOI: 10.3389/fphar.2016.00197

Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

Winnie de Bruijn et al. Front Pharmacol. 2016.

. 2016 Jul 22:7:197.

doi: 10.3389/fphar.2016.00197. eCollection 2016.

Authors

Affiliations

¹ Department of Pharmaceutical Sciences, Utrecht University Utrecht, Netherlands.
² Catalan Health Service - Servei Català de la Salut Barcelona, Spain.
³ Public Health Services Committee, Stockholm County Council Stockholm, Sweden.
⁴ Health Technologies and Pharmaceuticals, Division of Health Systems and Public Health, WHO Regional Office for Europe Copenhagen, Denmark.
⁵ Turkish Medicines and Medical Devices Agency, Ministry of Health Ankara, Turkey.
⁶ Independent Pharmaceutical Consultant Mellieha, Malta.
⁷ Croatian Health Insurance Fund Zagreb, Croatia.
⁸ Department of Finance, University of Vienna Vienna, Austria.
⁹ Ministry of Health Paris, France.
¹⁰ Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge Stockholm, Sweden.
¹¹ Department of Pharmacology, Ekiti State University Ado-Ekiti, Nigeria.
¹² Health Insurance Institute Ljubljana, Slovenia.
¹³ School of Medicine, The University of Notre Dame AustraliaDarlinghurst, NSW, Australia; Department of Pharmacology and Clinical Neuroscience, Umea UniversityUmea, Sweden.
¹⁴ School of Pharmacy, Graduate Program in Medicines and Pharmaceutical Assistance, Federal University of Minas GeraisBelo Horizonte, Brazil; Department of Social Pharmacy, SUS Collaborating Centre - Health Technology Assessment and Excellence in Health, College of Pharmacy, Federal University of Minas GeraisBelo Horizonte, Brazil.
¹⁵ Clinical Pharmacy, Rutgers State University of New JerseyPiscataway, NJ, USA; Horizon Blue Cross Blue Shield of New JerseyNewark, NJ, USA.
¹⁶ Scottish Medicines Consortium Glasgow, UK.
¹⁷ Pharmaceutical Drug Department, Azienda Sanitaria Locale of Verona Verona, Italy.
¹⁸ State Agency of Medicines Tartu, Estonia.
¹⁹ Ministry of Health and Child Care Harrare, Zimbabwe.
²⁰ Department of Health Services, Ministry of Health Reykjavík, Iceland.
²¹ Clinic for Infectious Diseases and Febrile Illnesses, University Medical Centre Ljubljana Ljubljana, Slovenia.
²² Faculty of Medicine, University of Banja LukaBanja Luka, Bosnia and Herzegovina; Ministry of Health and Social WelfareBanja Luka, Bosnia and Herzegovina.
²³ Department of Clinical Pharmacology, School of Medicine, University of Botswana Gaborone, Botswana.
²⁴ Clinical Pharmacology Unit, Department of Medicine, Lagos State University Teaching HospitalLagos, Nigeria; Department of Pharmacology and Therapeutics, Lagos State University College of MedicineLagos, Nigeria.
²⁵ National Centre for Pharmacoeconomics Dublin, Ireland.
²⁶ Hauptverband der Österreichischen Sozialversicherungsträger Wien, Austria.
²⁷ IRDES Paris, France.
²⁸ Department of Pharmaceutical and Pharmacological Sciences, KU Leuven Leuven, Belgium.
²⁹ Ministry of Health, Nelson Mandela Drive Gaborone, Botswana.
³⁰ Drug Utilisation Research Unit, Faculty of Health Sciences, Nelson Mandela Metropolitan University Port Elizabeth, South Africa.
³¹ Stockholms Läns Landsting, Hälso-och Sjukvårdsförvaltningen Stockholm, Sweden.
³² Faculty of Management, Comenius University Bratislava, Slovakia.
³³ HTA Consulting Cracow, Poland.
³⁴ School of Management and Business, King's College London London, UK.
³⁵ Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital HuddingeStockholm, Sweden; Strathclyde Institute of Pharmacy and Biomedical Sciences, University of StrathclydeGlasgow, UK.

PMID: 27516740
PMCID: PMC4964878
DOI: 10.3389/fphar.2016.00197

Abstract

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.

Keywords: Hepatitis C; boceprevir; cross national drug utilization study; demand-side measures; introduction new medicines; sofosbuvir; telaprevir.

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Figures

**Figure 1**
**Uptake BCV and TVR across European countries from the month first reimbursed**. Each Bar represents a 3 month period. Only the first quarter of 2012 and 2013 is displayed in the legend to include all countries. **(A)** Included countries are: AU, Austria; BE, Belgium; DK, Denmark; EE, Estonia; ES (CT), Catalonia (Spain). **(B)** Included countries are: IT, Italy; NL, the Netherlands; UK-Scot (TS), Tayside (Scotland); SI, Slovenia; SE, Sweden; TR, Turkey.

**Figure 2**
**Percentage utilization of TVR vs. ribavirin in quarters following reimbursement**. NB: Upper range genotype 1 prevalence (=GT1) is 65% and highest percentages (50%) triple therapy containing TVR (mostly non-cirrhotic patients). Lower range GT1 prevalence is only 45% and lowest percentages (25%) triple therapy containing TVR (mostly cirrhotic patients).

**Figure 3**
**Percentage utilization of BCV vs. ribavirin in quarters following reimbursement**. Upper range genotype 1 prevalence (=GT1) is 65% and highest percentages (92%) triple therapy containing BVC (mostly cirrhotic patients). Lower range GT1 prevalence is only 45% and lowest percentages (67%) triple therapy containing BVC (mostly naïve non-cirrhotic patients).

**Figure 4**
**Expenditure on treatments for HCV (Euro/1000 inhabitants/quarter) from 2008 to 2013**. NB: ◯ = reimbursement agreed BVC. Sweden and Denmark first quarter after EMA approval are included.

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[1] Adamski J., Godman B., Ofierska-Sujkowska G., Osiñska B., Herholz H., Wendykowska K., et al. . (2010). Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers. BMC Health Serv. Res. 10:153. 10.1186/1472-6963-10-153 - DOI - PMC - PubMed

[2] Adamski J., Godman B., Ofierska-Sujkowska G., Osiñska B., Herholz H., Wendykowska K., et al. . (2010). Risk sharing arrangements for pharmaceuticals: potential considerations and recommendations for European payers. BMC Health Serv. Res. 10:153. 10.1186/1472-6963-10-153 - DOI - PMC - PubMed

[3] Andrieux-Meyer I., Cohn J., de Araújo E. S. A., Hamid S. S. (2015). Disparity in market prices for hepatitis C virus direct-acting drugs. Lancet Glob. Heal. 3, e676–e677. 10.1016/S2214-109X(15)00156-4 - DOI - PubMed

[4] Andrieux-Meyer I., Cohn J., de Araújo E. S. A., Hamid S. S. (2015). Disparity in market prices for hepatitis C virus direct-acting drugs. Lancet Glob. Heal. 3, e676–e677. 10.1016/S2214-109X(15)00156-4 - DOI - PubMed

[5] Atun R., Aydın S., Chakraborty S., Sümer S., Aran M., Gürol I., et al. . (2013). Universal health coverage in Turkey: enhancement of equity. Lancet 382, 65–99. 10.1016/S0140-6736(13)61051-X - DOI - PubMed

[6] Atun R., Aydın S., Chakraborty S., Sümer S., Aran M., Gürol I., et al. . (2013). Universal health coverage in Turkey: enhancement of equity. Lancet 382, 65–99. 10.1016/S0140-6736(13)61051-X - DOI - PubMed

[7] Aygen B., Yıldız O., Akhan S., Çelen M. K., Ural O., Koruk S. T., et al. . (2015). Retreatment of Chronic Hepatitis C Infection with Telaprevir: preliminary results in Turkey. Balkan. Med. J. 32, 266–272. 10.5152/balkanmedj.2015.15366 - DOI - PMC - PubMed

[8] Aygen B., Yıldız O., Akhan S., Çelen M. K., Ural O., Koruk S. T., et al. . (2015). Retreatment of Chronic Hepatitis C Infection with Telaprevir: preliminary results in Turkey. Balkan. Med. J. 32, 266–272. 10.5152/balkanmedj.2015.15366 - DOI - PMC - PubMed

[9] Barua S., Greenwald R., Grebely J., Dore G. J., Swan T., Taylor L. E. (2015). Restrictions for medicaid reimbursement of sofosbuvir for the treatment of hepatitis C virus infection in the United States. Ann. Int. Med. 163, 215–223. 10.7326/M15-0406 - DOI - PubMed

[10] Barua S., Greenwald R., Grebely J., Dore G. J., Swan T., Taylor L. E. (2015). Restrictions for medicaid reimbursement of sofosbuvir for the treatment of hepatitis C virus infection in the United States. Ann. Int. Med. 163, 215–223. 10.7326/M15-0406 - DOI - PubMed

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Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

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Introduction and Utilization of High Priced HCV Medicines across Europe; Implications for the Future

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