This study analyzed the economic aspects of treatment options for pulmonary arterial hypertension from the perspective of the Brazilian public health system. An indirect comparison of clinical trials found similar efficacy for ambrisentan, bosentan, and sildenafil. The total annual costs per patient were estimated to be R$13,169.76 for ambrisentan, R$13,226.86 for sildenafil, and R$30,227.70 for bosentan, with drugs being the main cost driver. Probabilistic sensitivity analysis confirmed ambrisentan as the lowest cost option with similar clinical outcomes compared to other therapies.

1. ECONOMIC ANALYSIS OF TREATMENTS FOR PULMONARY ARTERIAL HYPERTENSION
FROM THE BRAZILIAN PUBLIC HEALTH SYSTEM PERSPECTIVE
C amila Pepe, Ale x andre Olimpio, Márcio Machado, Gisela Meyer
1 2 2 3
1. MedInsight Decisions in Healthcare, São Paulo, SP, Brasil
PCV47 This study was funded by GlaxoSmithKline Brazil . 2. GlaxoSmithKline Brasil, Rio de Janeiro, RJ, Brasil
3. Complexo Hospitalar Santa Casa de Misericórdia de Porto Alegre, Porto Alegre, RS, Brasil
Figure 3 - Probabilistic sensitivity analysis results
introduction results
Bosentan
• Pulmonary arterial hypertension (PAH) is a chronic disease characterized by progressive elevation of pulmonary artery • There were no studies directly comparing any of the targeted agents . Thus, an indirect comparison
6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16
Ambrisentan R$80,000.00
pressure and vascular resistance, leading to right-sided heart failure and premature death.1,2,3
of placebo controlled trials of selected PAH therapies was conducted. Standardized mean differences (SMD) between
ANNUAL TREATMENT COST
Sildenafil
R$70,OOO.00
• PAH treatment aims at improving disease symptoms, exercise tolerance, long-term results (i.e., prevent clinical agents (over placebo) was calculated and the magnitude of effects between the comparators suggested similar
worsening) and quality of life. clinical efficacy over 12–16 weeks of treatment (Figure 1). R$60,000.00
• Epidemiological data for PAH in Brazi is scarce .
2
• Confidence intervals of treatment effects overlapped substantially and supported the clinical assumption. R$50,000.00
• The total annual/monthly costs for the interventions were R$13,169.76/R$1,097.48 for ambrisentan, R$13,226.86/
R$40,000.00
objective R$1,102.24 for sildenafil, and R$30,227.70/R$2,518.98 for bosentan. (Figure 2)
• Disaggregated cost analysis showed drugs as the key economic driver (Table 1). R$30,000.00
• The objective of the present research was to assess the clinical and economic aspects of current oral treatments • Probabilistic sensitivity analysis confirmed base case results (Figure 3). R$20,000.00
options for PAH, New York Heart Association (NYHA) functional classes II and III, from the Brazilian Public Health System
R$10,000.00
perspective. conclusions 0
methods • Ambrisentan was identified as the alternative with the lowest cost and similar clinical outcomes compared with other
0 100 200 300 400 500 600 700 800 900 1000
NUMBER OF INTERATIONS
selected therapies for treating patients diagnosed with PAH, NYHA functional classes II and III, under the Brazilian public
• A literature review was conducted on the efficacy and safety of ambrisentan, bosentan and sildenafil in patients perspective.
diagnosed with PAH, in order to support the assumption of clinical equivalence between the treatments and the
development of a cost-minimization analysis. The clinical outcome of interest was improvement in the distance (in Figure 2 - Annual and monthly cost per patient with bosentan, ambrisentan and sildenafil
meters) walked in 6 minutes (6MWD). references
• For the economic analysis, direct medical costs were considered. Treatment, diagnostic, and procedure costs were Annual Cost
Monthly Cost R$35,OOO.00
obtained from public price/reimbursement databases. Government acquisition prices were used for all drugs .
4 5
R$30,227.70
1. Avaliação hemodinâmica da hipertensão pulmonar. Jornal Brasileiro de Pneumologia. 2005; 31 (Supl 2): S9 – S12
2. Lapa SM. Características clínicas dos pacientes com hipertensão pulmonar em dois centros de referência de SP. Rev Assoc Med Bras 2006; 52(3): 139-43
Eventual costs associated with adverse drug reactions and treatment withdrawals were also considered. R$30,000.00
3. Archer O, Rich S. Primary pulmonary hypertension: a vascular biology and translational research “Work in progress”. Circulation. 2000; 102(22): 2781-91
• PAH treatment protocols were the following: ambrisentan 5mg QD (titration to 10mg as per Ouriz et al., 2009 long- R$25,000.00
4. Sistema de Gerenciamento da Tabela de Procedimentos, Medicamentos e OPM do SUS. Ministério da Saúde - Secretaria de Atenção à Saúde - Departamento de
Informática do SUS/SE/MS.
term data ); bosentan 62,5mg BID in the first 4 weeks and 125mg BID in the following weeks; sildenafil 20mg TID.
12
5. Ministério da Saúde. Banco de Preço em Saúde. Available at: <http://portal2.saude.gov.br/bps/login.cfm> [Access in: 18/06/2010].
R$20,000.00
• A one-year time-horizon was used and all costs were presented in 2011 Brazilian currency (1BRL=0.60USD). 6. Rubin JL, Badesh DB, Barst RJ, et al. Bosentan Therapy for Pulmonary Arterial Hypertension. N Engl J Med 2002; 346(12):896-904
7. Galiè N, Rubin LJ, Hoeper MM et al. Treatment of patients with mildly symptomatic pulmonary arterial hypertension with bosentan (EARLY study): a double-blind,
• Second order Monte Carlo sensitivity analysis tested model robustness (1.000 model iterations used, ±30% variation R$15,000.00
R$13,169.76
R$13,226.86
randomised controlled trial. The Lancet 2008; 371:2093-2100.
in all parameters). R$10,000.00 8. Channick RN, Simonneau G, Sitbon Ol, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomized
placebo-controlled study. Lancet 2001; 358:1119-23
Figure 1 - Standardized mean differences relative to placebo in the 6-minute walk distance (m). R$5,000.00 R$2,518.98 9. Galie N, Beghetti M, Gatzoulis MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled
R$1,097.48 R$1,102.24 study. Circulation 2006; 114: 48-54
Study Standardized means difference 0 10. McLaughlin VV, Sitbon O, Badesch DB, et al. Survival with first-line Bosentan in patients with primary pulmonary hypertension. Eur Respir J 2005; 25: 244-9
(95% CI) AMBRISENTAM SILDENAFIL BOSENTAN 11. Galiè N, Olschewski H, Oudiz RJ, et al. Ambrisentan for the Treatment of Pulmonary Arterial Hypertension: Results of the Ambrisentan in Pulmonary Arterial
Hypertension, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Efficacy (ARIES) Study 1 and 2. Circulation 2008; 117:3010-3019
Oudiz 2007 (ambrisentan) 0.38 (0.04, 0.72) 12. Oudiz JR, Gali N, Olschewski H, et al. Long Term Ambrisentan Therapy for the Treatment of Pulmonary Arterial Hypertension. J Am Coll Cardiol 2009; 54(21):1971-81
Olschewsk et al. 2006 (ambrisentan) 0.70 (0.34, 1.06) 13. Denton CP, Humbert M, Rubin L, Black CM. Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of
Rubin et al. 2002 (bosentan) 0.33 (0.00, 0.65)
the pivotal clinical trials and their open-label extensions. Ann Rheum Dis. 2006 Oct;65(10):1336-40.
14. Galie` N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148-57.
Channick et al. 2001 (bosentan) 0.80 (0.05, 1.56) Table 1 - Dissaggregated cost analysis 15. Oudiz RJ. Long term ambrisentan therapy provides sustained benefit in patients with pulmonary arterial hypertension [abstract]. Chest 2007; 132: 474s.
Galiè et al. 2006 (bosentan) 0.81 (0.22, 1.41) 16. Olschewski H, Galie` N, Kramer M, et al. Ambrisentan improves exercise capacity and time to clinical worsening in patients with pulmonary arterial hypertension:
Galiè et al. 2005 (sildenafil) 0.36 (0.02, 0.69)
annual treatment cost results of the ARIES-2 study [abstract]. 102nd International Conference of the American Thoracic Society; 2006 May 19-24; San Diego (CA)
type of cost
Bosentan Ambrisentan Sildenafil
Standardized mean difference
-0.5 0 0.5 1.0 1.5 Drugs R$29,628.69 R$12,680.28 R$12,745.74
Standardized mean differences (Cohen’s d) for individual studies relative to placebo in the 6-minute walk distance (m). Heterogeneity between trials: chi-squared (X2) = 5.23
Adverse reactions R$329.14 R$155.47 R$171.28
(degrees of freedom = 7); p=0.632. Oudiz, Olschewski et al., Rubin et al., Channick et al., Galiè et al., Barst et al., Galiè et al. Adapted from: Dranitsaris, G; Mehta S. Oral Therapies Clinical worsening (hospitalization) R$19.50 R$15.11 R$15.06 ISPOR 17th Annual International Meeting
for the Treatment of Pulmonary Arterial Hypertension A Population-Based Cost-Minimization Analysis. Appl Health Econ Health Policy 2009; 7 (1). 43-59. Physician visits and lab tests R$249.83 R$318.90 R$294.78 Washington, DC, USA - June, 2012.
Total R$30,227.16 R$13,169.76 R$13,226.86