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Prevalence of pulmonary arterial hypertension in the Camerino area of central Italy and savings resulting from generic bosentan
  1. Sonia Natali1,
  2. Martina Palmieri1,
  3. Carlo Polidori2
  1. 1 Hospital Pharmacy of the Santa Maria Hospital of Camerino, Camerino, Italy
  2. 2 Experimental Medicine and Public Health Department, University of Camerino, Camerino, Italy
  1. Correspondence to Dr. Sonia Natali, Hospital Pharmacy of the Santa Maria Hospital of Camerino, Camerino 62032, Italy; sonia.natali{at}sanita.marche.it

Abstract

Objective Pulmonary arterial hypertension is a rare and progressive respiratory disease characterised by high blood pressure and vascular resistance producing right ventricular fatigue. In Italy, pulmonary hypertension can be treated with different drugs available on the market at different costs, and in the Marche region distributed exclusively by hospital pharmacies. The present study examined in an area of the Marche region the use of drugs specifically indicated for pulmonary hypertension, and evaluated how the introduction of the generic bosentan might lower pharmaceutical costs for the healthcare budget.

Methods The study examined oral administration prescriptions and costs using data from the Apotheke Gold (Record Data) database from 1 January 2012 to 31 August 2017.

Results Annually (from 1 January 2012 to 31 August 2017), an average of 4.83 patients were treated (prevalence of 102.35 cases per 1 million residents) with ambrisentan (Volibris), bosentan (Tracleer), macitentan (Opsumit), tadalafil (Adcirca) or sildenafil (Revatio). The total expenditure during the 5-year 8-month period was €472 405. Ambrisentan was by far the most expensive product overall, with a total expenditure of €222 380 for the period studied (a daily cost of €67.39), even though Tracleer had the highest cost for a day of treatment (a daily cost of €94.48, but a total expenditure of €163 976 for the period, due to its more recent marketing). Providing patients with the generic form bosentan in place of Tracleer would lower the costs dramatically. A very significant annual savings per patient of approximately €31 879 would be achieved, a striking 92.4% reduction in costs.

Conclusion The prevalence of pulmonary arterial hypertension reported for Camerino and its surrounding area in the Marches region is quite high compared with that reported by other authors for France and Scotland. The introduction of the generic bosentan would cut costs drastically. It is to be hoped that centralised procurement at the regional level would bring further savings.

  • pharmacoeconomics
  • pharmacy management (organisation, financial)
  • drug procurement
  • ethics (see medical ethics)
  • health economics
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Introduction

Pulmonary arterial hypertension is a rare disease characterised by pathophysiological conditions that can affect cardiovascular, pulmonary and haematological system functions.

In the last classification made by WHO experts, pulmonary hypertension was divided into five subgroups, related to the underlying cause of the disease:

  1. Pulmonary arterial hypertension.

  2. Pulmonary hypertension caused by left-sided heart disease.

  3. Pulmonary hypertension caused by parenchymal lung disease and/or hypoxaemia.

  4. Thromboembolic chronic pulmonary heart.

  5. Pulmonary hypertension associated with unclear and multifactorial pathogenic mechanism.

The first subgroup is a rare and progressive respiratory disease characterised by high blood pressure and vascular resistance; it determines right ventricular fatigue with cardiac failure that, in some cases, can lead to death. Left untreated, pulmonary arterial hypertension leads to death of patients approximately 2.8 years after diagnosis, while the life expectancy of patients receiving appropriate treatment is on average 5 years.1 2

Up to 2017, no epidemiological studies on pulmonary hypertension have been available for Italy. The only studies for Europe were conducted in France and Scotland and reported a disease incidence of 2.4–7.6 new cases per year per 1 million inhabitants.3 4 However, an indirect study of the prevalence of this rare disease, based on drug distribution throughout Italy, was published in 2010 by Guidi and Mignini.5

In the French study published in 2006, the prevalence and incidence estimates for the period October 2002–October 2003 were 15 and 2.4 cases per million residents in France, respectively,3 based on a registry produced by the French Reference Center for Pulmonary Arterial Hypertension. In the period 2000–2002, the Centre recruited 17 university hospital centres in France that treated at least five newly diagnosed patients per year. Between October 2002 and October 2003, all the patients observed by the centres were included in the registry.

In the Scottish study published in 2007, Peacock and colleagues4 collected data on hospitalisations for pulmonary arterial hypertension in Scotland and compared them with the information from the Scottish Pulmonary Vascular Unit (SPVU). The Scottish Morbidity Record Scheme documented all patients between 16 and 65 years hospitalised for the idiopathic subtype, for the congenital cardiovascular form and for the connective tissue diseases of pulmonary hypertension identified in the period of observation from 1986 and 2001. The annual incidence was 7.1 new cases per million residents, while the prevalence estimate was 52 cases per million residents. The SPVU data regarded the period from 1997 to 2006; 2005 was the last year with complete data, and the incidence of the disease for this year was 7.6 cases per million residents, with a corresponding prevalence of 26 cases per million residents.4 The guidelines for the diagnosis and treatment of pulmonary arterial hypertension, which include a summary of the data described above,2 were published in 2015 by the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology and by the European Respiratory Society, supported by the International Society of Heart and Lung Transplantation.

In the present study, we applied to the Italian population the Humbert et al 3 and Peacock et al 4 prevalence data, indicating a minimum and a maximum number of pulmonary arterial hypertension cases in order to estimate how many patients were treated in the period studied and calculate how much was spent to treat this disease. Based on these two studies and taking into consideration the population of the 20 Italian regions (drawn from the Italian National Statistics Institute (ISTAT) reports from 1 January 20096), the estimated prevalence of the disease ranges from 900 to 3122 cases. The regions with the lowest number of cases are Valle D’Aosta (2–7 cases) and Molise (5–17 cases), while the regions with the highest number of cases are Lombardia (146–507 cases) and Campania (87–302 cases).5

As mentioned above, an indirect analysis of prevalence was reported by Guidi and Mignini,5 on the basis of analysis of the sales of a medication specifically prescribed for pulmonary arterial hypertension. Their estimated prevalence value for Italy was higher than those of Humbert et al for France3 and Peacock et al for Scotland.4 Indeed, the Guidi and Mignini5 study indicated a prevalence range of 39–51 cases per 1 million inhabitants, in relation to the use of the lowest dose (20 mg three times a day) or the highest dose (80 mg three times a day) of sildenafil; the annual cost (for the period 2007–2009) was €876 969.38.

The present epidemiological study used the methodology of the Humbert et al 3 and Peacock et al 4 studies to estimate how many inhabitants of the Camerino area, one of the 13 geographical areas of the Marches regional public healthcare system, are affected by this rare disease. The population of the entire region is about 1 538 055 inhabitants, according to the January 2017 ISTAT data, and the population for the city of Camerino and its surrounding area is 47 190 residing inhabitants. The Marche region public healthcare system is organised into five major areas (area vasta) that cover a total of 13 major cities and surrounding areas. Each area vasta is responsible for about two or three major cities and their surrounding areas. Area Vasta 3—Camerino includes the cities of Camerino, Civitanova and Macerata. This study focused specifically on the city of Camerino and its surrounding area.

The objective of our study was to measure the consumption of medicines with a specific indication for pulmonary hypertension, namely the endothelin receptor antagonists ambrisentan, bosentan and macitentan, or the phosphodiesterase type-5 inhibitors tadalafil and sildenafil citrate (see table 1), and to determine the savings that might be possible by providing the generic form bosentan rather than the expensive brand Tracleer.

Methods

In order to estimate the prevalence of pulmonary arterial hypertension in the Camerino area, we looked at the annual average number of patients provided drugs for pulmonary arterial hypertension by the pharmaceutical service of the Camerino hospital. To do so, we examined prescriptions for the oral administration drugs using the Apotheke Gold (Record Data), a software given to hospital pharmacies for analysis of pharmaceutical prescriptions both in the hospital and in community pharmacies, focusing on the period from 1 January 2012 to 31 August 2017 (the last month of patent coverage for Tracleer). We report the value as the number of cases treated, out of one million residing inhabitants, in order to allow a comparison with other findings in the literature.3 4

In order to estimate the cost of treatment for each drug, we considered the cost of a day of therapy, in line with the 2010 Guidi and Mignini methodology,5 calculated according to the current dosages specified in an up-to-date Italian pharmaceutical database that serves pharmacies and other businesses in the pharmaceutical sector (data source: Farmadati Italia, March 2018).

Results

Based on our examination of prescriptions for drugs to treat pulmonary arterial hypertension, we found a female to male ratio of 2:7. The average age at the time of the study was 63±15.93 years (mean±SD); the average annual number of patients treated was 4.83, which corresponds to a prevalence of 102.35 cases per 1 million residing inhabitants.

Not considering the year 2017, as data are available only until 31 August, the total annual expenditure for patients in Camerino and its surrounding area ranged from a low of €60 883 (in 2016) to a high of €99 783 (in 2013), with a fluctuating trend over the years. The total expenditure for the entire period of 2012–2016 was €472 404 (table 1). As can be seen in table 1, ambrisentan was by far the most expensive product overall, with a total expenditure of €222 376 for the period studied (a daily cost of €67.39), even though Tracleer had the highest cost for a day of therapy (a daily cost of €94.48, but with a total expenditure of €163 976 for the period, due to its more recent marketing). If Tracleer were to be replaced with the generic bosentan, which costs only €7 for a day of treatment, the Camerino area healthcare system could achieve annual savings per patient of €31 879, a striking 92.4% reduction in costs.

Table 1

Expenditure data for the city of Camerino and its surrounding area, which is part of the ASUR Marche—Area Vasta 3—area of Camerino

Discussion

The small sample population examined could represent a limitation to this work. Pulmonary arterial hypertension is a rare disease and the population of the city of Camerino and its surrounding area is limited (47 190 residing inhabitants).

Further study would be advisable, as our estimate of the prevalence of pulmonary arterial hypertension in the Camerino area (102.35 cases per million) is markedly higher than that reported for France (15 cases per million) and Scotland (26–52 cases per million).3–5 Indeed, according to the literature, the Camerino value should have been found between 0.72 and 2.51 cases per million.

The choice to restrict the study to orally administered drugs with a specific indication for pulmonary arterial hypertension was necessary in order to compare our results with those derived with a similar methodology5 and therefore to evaluate the costs.

A different estimation would have been difficult to carry out due to the variety of treatment schemes possible for pulmonary arterial hypertension and the frequent usage of non-pharmacological treatments or off-label use of drugs.

The choice to treat pulmonary arterial hypertension with the generic bosentan rather than the Tracleer brand over a period of 1 year could save the Marche region over €2 million. Were the national healthcare system to implement the same change, the Italian government could save almost €78 million in a year.

Conclusions and considerations

The prevalence of pulmonary arterial hypertension in the Camerino area is markedly higher than that reported in the literature.3–5

In sum, on the basis of our findings for Camerino and its surrounding area, the introduction of the generic bosentan to the entire Marche region would have a very significant impact on the pharmaceutical budget. It would also be advisable to organise a centralised procurement procedure for the region which would enhance the ability to negotiate favourable prices. These two initiatives could free financial resources which would hopefully be dedicated to scientific research on finding a cure for this rare and deadly pathology.

What this paper adds

What is already known on this subject

  • Pulmonary arterial hypertension is a rare and progressive respiratory disease characterised by pathophysiological conditions that can affect cardiovascular, pulmonary and haematological system functions.

  • The generic bosentan, a drug for the treatment of the disease, came to the market in late 2017.

What this study adds

  • This work shows that significant savings are possible through the choice of a generic drug to treat pulmonary hypertension in the Camerino hospital area, which it is hoped could be extended to the entire Marche region through a centralised procurement procedure.

References

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Footnotes

  • EAHP statement 2: selection, procurement and distribution.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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