Compras públicas de medicamentos para hepatite C no Brasil no período de 2005 a 2015 / Public procurement of hepatitis C medicines in Brazil from 2005 to 2015

Resumo O artigo analisa as compras de medicamentos para hepatite C, feitas pelo Ministério da Saúde (MS), de 2005 a 2015. Os dados são do Sistema Integrado de Administração de Serviços Gerais (SIASG). Para estimar o gasto contratado anual selecionou-se medicamentos previstos nos Protocolos Clínicos e Diretrizes Terapêuticas para Hepatite C do MS e incluiu-se todas as apresentações e concentrações que apareceram no SIASG. Houve aumento de 159,5 vezes no gasto com os medicamentos selecionados de 2005 a 2006 porque esses produtos passaram a ser comprados de forma centralizada. Em 2007 houve aumento de 730% no gasto pela incorporação de alfapeginterferona 2a e 2b. Em 2012 a compra de dois novos antivirais de ação direta (AAD) representou 99% do gasto anual. Em 2015, a adoção de novos AAD provocou aumento de 230% (R$ 945 milhões) no gasto do MS. No período estudado houve aumento dos gastos do MS com os medicamentos para Hepatite C devido ao aumento do volume adquirido e à incorporação tecnológica de alfapeginterferona e de novos AAD. Garantir acesso universal ao tratamento da hepatite C depende da implementação de estratégias que aumentem o poder de barganha do MS em negociações de redução de preços de produtos em situação de monopólio.

Abstract This paper analyzes the Minister of Health's (MoH) procurement of medicines for hepatitis C from 2005 to 2015. Data sources were the Integrated General Services Administration (SIASG), to estimate annual expenditure for selected medicines of the MoH Clinical Protocols and Therapeutic Guidelines (PCDT) for Hepatitis C. All presentations and strengths recorded on SIASG were included. The unit prices were estimated based on the purchase with the highest volume each year. There was a 159.5 fold increase in expenditure of the selected medicines from 2005 to 2006, because procurement of those medicines became centralized. In 2007 there was 730% increase in spending due to the incorporation of pegainterferons alfa 2a and 2b. In 2012 the purchase of only two new direct-acting antivirals (DAA) accounted for 99% of total annual expenditure. In 2015 the adoption of a new DAA led to an increase of 230% (R$945 million) in MoH spending. The significant increase of MoH expenditure on medicines for hepatitis C from 2005 to 2015 was due to the increase of volumes purchased as well as the incorporation of alfapeginterferon and new DAAs. Ensuring universal access to treatment for hepatitis C will depend on the implementation of strategies that strengthen the MoH's bargaining power in price reduction negotiations with the manufacturers of monopoly medicines.

Custo-efetividade da inclusão dos respondedores virológicos lentos no tratamento da hepatite C na presença da coinfecção com o HIV / Cost-effectiveness of hepatitis C treatment in slow virologic responders coinfected with HIV / Coste-efectividad del tratamiento de la hepatitis C en coinfectados con el VIH con respuesta virológica lenta

Evidências recentes demonstram que respondedores virológicos lentos podem se beneficiar com a extensão do tratamento antiviral. O estudo investigou a adoção desse protocolo diante da coinfecção VHC/HIV. O objetivo foi estudar a relação de custo/efetividade da terapêutica com peguinterferon associado à ribavirina em portadores do genótipo 1 do VHC coinfectados com o HIV, comparando-se a inclusão ou não de respondedores virológicos lentos. Simulou-se por meio de um modelo de Markov a progressão da doença hepática em uma coorte hipotética de mil homens, maiores de 40 anos, considerandose a perspectiva do Sistema Único de Saúde (SUS) e horizonte temporal de 30 anos. A extensão do tratamento para respondedores lentos resultou em uma razão incremental de custo efetividade de R$ 44.171/QALY, valor abaixo do limiar de aceitabilidade proposto pela Organização Mundial da Saúde. A análise de sensibilidade não modificou os resultados alcançados. A inclusão de indivíduos coinfectados VHC/HIV respondedores virológicos lentos no protocolo de tratamento apresenta-se como uma estratégia custo-efetiva para o SUS.

Recent evidence has demonstrated that slow responders may benefit from antiviral treatment in HCV/HIV coinfection. This study aimed to evaluate the cost-effectiveness of HCV treatment in individuals with genotype 1 coinfected with HIV, with peg-interferon in combination with ribavirin, compared to the inclusion (versus non-inclusion) of slow responders. A Markov model was developed that simulated the progression of liver disease in a hypothetical cohort of one thousand men over 40 years of age, considering the Brazilian Unified National Health System (SUS) perspective and a 30-year timeline. The extension of treatment to slow responders provided a 60% increase in the number of individuals who eliminated HCV and an incremental cost-effectiveness ratio of 44,171 BRL/QALY, below the acceptability threshold proposed by World Health Organization. Sensitivity analysis did not alter the results. The inclusion of HCV/ HIV-coinfected slow virologic responders in the treatment protocol is shown to be a cost-effective strategy for the SUS.

La evidencia reciente ha demostrado que los individuos con respuesta virológica lenta pueden beneficiarse de una extensión del tratamiento antiviral. El estudio investigó la adopción de este protocolo antes de la coinfección por VHC/HIV. El objetivo fue estudiar la relación coste-efectividad de la terapia con peginterferon asociado con ribavirina en pacientes con genotipo 1 del VHC, coinfectados por el HIV respondedores virológicos lentos. Se simula mediante un modelo de Markov la progresión de la enfermedad hepática en una cohorte hipotética de un millar de hombres, más de 40, teniendo en cuenta la perspectiva del Sistema Único de Salud (SUS) y un horizonte temporal de 30 años. El grado de tratamiento a los respondedores lentos dio lugar a un incremento de coste-efectividad de R$ 44.171/QALY, por debajo del umbral de aceptabilidad propuesto por la Organización Mundial de la Salud. El análisis de sensibilidad no modificó los resultados. La inclusión de los individuos coinfectados y con respuesta virológica lenta en el protocolo de tratamiento se presenta como una estrategia económica para el SUS.

Economic evaluation of treatments for chronic hepatitis B

The aim of this study was to conduct a cost-utility study of adefovir, entecavir, interferon alpha, pegylated interferon alpha, lamivudine and tenofovir for chronic hepatitis B in the context of Brazilian Public Health Care System. A systematic review was carried out for efficacy and safety. Another review was performed to collect utility data and transition probabilities between health states. A Markov model was developed in a time horizon of 40 years with annual cycles for three groups of: HBeAg positive, HBeAg negative, and all patients. These strategies were compared to a fourth group that received no treatment. Discount rates of 5% were applied and sensitivity analyses were performed. Tenofovir offered the best cost-utility ratio for the three evaluated models: U$397, U$385 and U$384 (per QALY, respectively, for HBeAg positive, negative, and all patients). All other strategies were completely dominated because they showed higher costs and lower effectiveness than tenofovir. The sequence of cost-utility in the three models was: tenofovir, entecavir, lamivudine, adefovir, telbivudine, pegylated interferon alpha, and interferon alpha. In the sensitivity analysis, adefovir showed lower cost-utility than telbivudine in some situations. The study has some limitations, primarily related to the creation of scenarios and modeling. In this study, tenofovir presented the best cost-utility ratio. The results obtained in this study will be valuable in decision-making and in the review of the clinical protocol, mainly involving the allocation of available resources for health care.

Cost effectiveness of peginterferon alfa-2B combined with ribavirin for the treatment of chronic hepatitis C in Brazil

The treatment of chronic hepatitis C (CHC) with peginterferon alpha-2b/ribavirin (PegIFN + Rib) produced larger sustained viral response (SVR) compared to the conventional (non-pegylated) interferon/ribavirin (IFN + Rib), but its cost-effectiveness was not assessed in Brazil. We developed a Markov model to mirror the natural disease history and cohorts of patients with hepatitis C virus (HCV), that received PegIFN + Rib or IFN + Rib treatment for 48 or 24 weeks, according to viral genotype and liver histology. The SVRs for the treatments PegIFN + Rib and IFN + Rib were respectively 48 percent and 34 percent (genotype 1), and 88 percent and 80 percent (genotype non-1). Three Delphi panels were conducted with hepatologists and intensivists, and another one with oncologists. The costs are expressed in 2006 Brazilian Reais (R$) and the benefits were discounted at 3 percent. In genotype 1 HCV patients, PegIFN + Rib increases the life expectancy (LE) in 0.51 year, and the quality-adjusted life years (QALY) in 0.78, as compared to IFN + Rib. In genotype non-1 HCV patients, PegIFN + Rib increases the LE in 0.29 years and the QALY in 0.44 years, as compared to IFN + Rib. The incremental cost-effectiveness rate, considering all the genotypes, was of R$19,848.34 per QALY. Peginterferon alpha-2b with ribavirin is a cost-effective therapy for the treatment of naïve CHC adult patients compared to the interferon alpha-2b and ribavirin regime, irrespective of the viral genotype.