Hepatitis C disease burden and strategies for elimination by 2030 in Brazil. A mathematical modeling approach

ABSTRACT Introduction and aim: Hepatitis C is a key challenge to public health in Brazil. The objective of this paper was to describe the Brazilian strategy for hepatitis C to meet the 2030 elimination goal proposed by World Health Organization (WHO). Methods: A mathematical modeling approach was used to estimate the current HCV-infected Brazilian population, and to evaluate the relative costs of two different scenarios to address HCV disease burden in Brazil: (1) if no further changes are made to the HCV treatment program in Brazil; (2) where the WHO targets for 2030 elimination are met through diagnosis and treatment efforts peaking before 2024. Results: An anti-HCV prevalence of 0.53% was calculated for the total population. It was estimated that the number of HCV-RNA+ individuals in Brazil in 2017 was 632,000 (0.31% of the population). Scale-up of treatment and diagnosis over time will be necessary in order to achieve WHO targets beginning in 2018. Direct costs (diagnostic, treatment and healthcare costs) are projected to increase significantly during the scale-up of treatment and diagnosis in the initial years of the intervention scenario, but then fall below the base case on an annual basis by 2025-2036, once HCV is eliminated, due to health sectors savings from the prevention of HCV liver-related morbidity and mortality. Conclusion: Achieving the WHO targets is technically feasible in Brazil with a scale-up of treatment and diagnosis over time, beginning in 2018. However, elimination of hepatitis C requires policy changes to substantially scale-up prevention, screening and treatment of HCV, together with public health advocacy to raise awareness among affected populations and healthcare providers.

Acciones prioritarias para un programa nacional de detección, tratamiento y seguimiento de pacientes con hepatitis C / Priority actions towards a national program for detection, treatment, and monitoring of patients with hepatitis C

Resumen: En el escenario de la salud mexicana, la epidemia por virus de la hepatitis C se encuentra presente junto con sus comorbilidades y mortalidad prematura. Actuar de manera inmediata permitirá una contención de la misma en el corto plazo dada la existencia de herramientas de prevención, diagnóstico y terapias farmacológicas altamente eficaces. La Coalición para el estudio de la hepatitis C en México ha desarrollado una postura donde aprovecha esas medidas de contención y presenta el desarrollo de un programa nacional para la detección, tratamiento oportuno y seguimiento de pacientes con hepatitis C.

Abstract: In the Mexican health scenario, the hepatitis C virus epidemic is present, along with its comorbidities and premature mortality. Acting immediately will allow its containment in short term with the proper implementation of the current available tools for prevention, diagnosis and highly effective pharmacological therapies. The Coalition for the study of hepatitis C in Mexico has developed a position paper that takes advantage of these containment measures and presents the development of a National program for the detection, timely treatment and follow-up of patients with hepatitis C.

Characteristics of a hepatitis C patient cohort at a specialized tertiary care facility: Identifying criteria to improve the allocation of public health resources

OBJECTIVES: Our objective was to analyze, in a population treated for hepatitis C infection at a tertiary care treatment unit, the prevalence of comorbidities and extrahepatic manifestations, the range and degree of the clinical complexity and the associations between advanced liver disease and clinical variables. METHODS: Medical records from chronically infected hepatitis C patients seen at a dedicated treatment facility for complex cases in the Infectious Diseases Division of Hospital das Clínicas in Brazil were analyzed. Clinical complexity was defined as the presence of one or more of the following conditions: advanced liver disease (Metavir score F3 or F4 and/or clinical manifestations or ultrasound/endoscopy findings consistent with cirrhosis) or hepatocellular carcinoma and/or 3 or more extrahepatic manifestations and/or comorbidities concomitantly. RESULTS: Among the 1574 patients analyzed, only 41% met the definition of being clinically complex. Cirrhosis or hepatocarcinoma was identified in 22.2% and 1.8% of patients, respectively. According to multiple logistic regression analysis, male sex (p=0.007), age>40 years (p<0.001) and the presence of metabolic syndrome (p=0.008) were independently associated with advanced liver disease. CONCLUSION: The majority of patients did not meet the criteria for admittance to this specialized tertiary service, reinforcing the need to reevaluate public health policies. Enhanced utilization of existing basic and intermediate complexity units for the management of less complex hepatitis C cases could improve care and lower costs.

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.

Avaliação econômica das abordagens terapêuticas para o tratamento das hepatites B e C: comparação das diretrizes nacionais e internacionais / Economic evaluation of therapeutic approaches for the treatment of hepatitis B and C: comparison of national and international guidelines

As hepatites virais B e C, nas últimas décadas, emergiram e se mantiveram em evidência como um grande problema de saúde pública. O desenvolvimento e a disseminação do uso de medicamentos antivirais vêm contribuindo para a diminuição da carga dessas infecções em nível individual e coletivo. Especialmente na última década, disponibilizaram-se tecnologias mais seguras e eficazes para o diagnóstico precoce e para o tratamento. No intuito de assegurar o uso racional desses insumos, muitos países elaboraram recomendações que incluem, os critérios de inclusão e exclusão para o tratamento e o estabelecimento do curso terapêutico. As recomendações nacionais e internacionais para o tratamento das hepatites B e C divergem em diversos aspectos, principalmente no que se refere aos fármacos eleitos como primeira linha de tratamento e ao público prioritário. No caso da hepatite C, o Ministério da Saúde brasileiro indica a terapia tripla somente para portadores de doença hepática avançada. O consenso internacional, representado pela OMS, pela AALSD e pelo NICE, assume direção oposta, ao propor como público prioritário, indivíduos com hepatite leve e moderada. As recomendações nacionais e internacionais para o tratamento da hepatite B se assemelham em grande medida, mas são conflitantes no que diz respeito aos medicamentos eleitos como primeira escolha. Com base nas divergências das diretrizes terapêuticas nacionais e internacionais, esse estudo objetivou confrontar as óticas nacionais e internacionais e avaliar as estratégias mais custo-efetivas para o tratamento contra o vírus da hepatite B (VHB) e o vírus da hepatite C (VHC) sob a perspectiva do SUS. Os resultados do modelo econômico construído indicam que o uso precoce e universal dos inibidores de protease (IPs) emerge como a conduta mais racional para o tratamento da hepatite C crônica na atualidade. Essa abordagem resulta em melhores desfechos clínicos e econômicos se comparada à terapia dual (peguinterferon + ribavirina) e ao uso de IPs no caso de refratariedade ao tratamento prévio e especialmente quando empregada restritamente aos casos de fibrose avançada, tal como recomendado pelas diretrizes nacionais. Na avaliação do custo-efetividade das recomendações terapêuticas para o tratamento contra o VHB em indivíduos HBeAg não reagentes, o uso do tenofovir se mostrou a estratégia mais eficiente. A terapia com tenofovir constitui a primeira linha de tratamento nas diretrizes nacionais atuais e foi a que apresentou maior efetividade associada ao menor custo global, contrariando as proposições de protocolos internacionais e de algumas publicações anteriores. Em síntese, a análise farmacoeconômica comparativa entre as diretrizes nacionais e internacionais para o tratamento das hepatites crônicas revela que a conduta de tratamento contra o VHB adotada no Brasil é adequada pelos pontos de vista clínico e econômico. Em contrapartida, as mesmas conclusões não se aplicam ao caso do tratamento da infecção do genótipo 1 da hepatite C, que, da forma como está sendo conduzido, penaliza uma parcela significativa dos indivíduos portadores, por oferecer o que há de mais avançado em tratamento antiviral exclusivamente aos pacientes com menores chances de resposta, maior risco de desenvolvimento de intolerância medicamentosa e já em estágio terminal da doença hepática

In the last decades, viral hepatitis B and C have emerged and have remained in evidence as a major public health problem. The development and dissemination of the use of antiviral drugs has contributed to reduce the burden of these infections at the individual and collective levels. Especially in the last decade, safer and more effective technologies have been made available for early diagnosis and treatment. In order to ensure the rational use of antivirals, many countries have developed recommendations that adds the inclusion and exclusion criterias for the treatment and establishment of the therapeutic course. National and international recommendations for the treatment of hepatitis B and C differ in several respects, especially for the drugs chosen as the first treatment line and for the priority public. In the case of hepatitis C, the Brazilian Ministry of Health indicates triple therapy only for patients with advanced liver disease. The international consensus, represented by WHO, AALSD and NICE, assumes the opposite direction proposing as a priority public, individuals with mild and moderate hepatitis. National and international recommendations for the treatment of Hepatitis B closely resemble each other but are in conflict with regard to medicines chosen as the first choice. Based on divergences among national and international therapeutic guidelines, this study aimed to compare national and international perspectives and to evaluate the most cost-effective strategies for the treatment of hepatitis B virus (HBV) and hepatitis C virus (HCV) from the SUS perspective. The results of the constructed economic model indicate that the early and universal use of protease inhibitors (PIs) emerges as the most rational conduct for the treatment of chronic hepatitis C today. This approach results in better clinical and economic outcomes compared to dual therapy (peginterferon + ribavirin) and the use of PIs in the case of refractoriness to previous treatment and especially when used strictly to cases of advanced fibrosis, as recommended by the national guidelines. In cost-effectiveness evaluation of the therapeutic recommendations for the treatment against HBV in non-reactive HBeAg individuals, the use of tenofovir was the most efficient strategy. In current national guidelines, tenofovir is recommended as the first-line treatment and was the one with the highest effectiveness associated with the lowest overall cost, contrary to the proposals of international protocols and some previous publications. In summary, the comparative pharmacoeconomic analysis between the national and international guidelines for the treatment of chronic hepatitis reveals that the treatment approach against HBV adopted in Brazil is adequate from the clinical and economic points of view. In contrast, the same conclusions do not apply to the treatment of hepatitis C genotype 1 infection, which, as it is being conducted, penalizes a significant portion of carriers because it offers the most advanced antiviral treatment exclusively to patients with lower chances of response, higher risk of developing drug intolerance and already in the terminal stage of liver disease

Medicamentos de dispensação excepcional: histórico e gastos do Ministério da Saúde do Brasil / Medicamentos de dispensación excepcional: historia y gastos del Ministerio de la Salud de Brasil / Exceptional circumstance drug dispensing: history and expenditures of the Brazilian Ministry of Health

OBJETIVO: Descrever aspectos técnicos do Programa de Medicamentos de Dispensação em Caráter Excepcional do Ministério de Saúde do Brasil, especialmente em relação aos gastos com os medicamentos distribuídos. MÉTODOS: Os aspectos técnicos foram obtidos por meio de consulta a todas as portarias que regulamentaram o Programa. Gastos no período de 2000 a 2007 foram obtidos do Sistema de Informações Ambulatoriais do Sistema Único de Saúde. Foram analisados os medicamentos dispensados de 1993 a 2009, quantidades e valor de cada procedimento informados nas autorizações de procedimentos de alta complexidade para cada estado. RESULTADOS: O Programa mudou, com aumento do número de fármacos e apresentações farmacêuticas distribuídas e de doenças contempladas. Eram distribuídos 15 fármacos em 31 diferentes apresentações farmacêuticas em 1993, passando para 109 fármacos em 243 apresentações em 2009. Os gastos totais do Ministério da Saúde com medicamentos somaram, em 2007, R$ 1.410.181.600,74, quase o dobro do valor gasto em 2000: R$ 684.975.404,43. Algumas das doenças que representaram maiores gastos nesse período foram: insuficiência renal crônica, transplante e hepatite C. CONCLUSÕES: O Programa de Medicamentos de Dispensação em Caráter Excepcional está em constante transformação, visando aprimorar os instrumentos e estratégias que assegurem e ampliem o acesso da população aos medicamentos. Devem-se buscar alternativas para reduzir o impacto financeiro do Programa para que não haja prejuízos às outras áreas do sistema de saúde, dado o custo elevado das novas tecnologias.

OBJETIVO: Describir aspectos técnicos del Programa de Medicamentos de Dispensación en Carácter Excepcional del Ministerio de Salud de Brasil, especialmente con relación a los gastos con los medicamentos distribuidos.MÉTODOS: Los aspectos técnicos fueron obtenidos por medio de consulta a todas los reglamentos que rigen el Programa. Gastos en el período de 2000 a 2007 fueron obtenidos del Sistema de Informaciones Ambulatorias del Sistema Único de Salud. Se analizaron los medicamentos dispensados de 1993 a 2009, cantidades y valor de cada procedimiento, informado en las autorizaciones de procedimientos de alta complejidad para cada estado.RESULTADOS: El Programa cambió, con aumento del número de fármacos y presentaciones farmacéuticas distribuidas y de enfermedades contempladas. Eran distribuidos 15 fármacos en 31 diferentes presentaciones farmacéuticas en 1993, pasando para 109 fármacos en 243 presentaciones en 2009. Los gastos totales del Ministerio de Salud con medicamentos sumaron, en 2007, R$ 1.410.181.600,74, casi el doble del valor gastado en el año 2000: R$ 684.975.404,43. Algunas enfermedades que representaron mayor gastos en ese período fueron: insuficiencia renal crónica, trasplante y hepatitis C. CONCLUSIONES: El Programa de Medicamentos de Dispensación en Carácter Excepcional está en constante transformación, buscando mejorar los instrumentos y estrategias que aseguren y amplíen el acceso de la población a los medicamentos. Se deben buscar alternativas para reducir el impacto financiero del Programa para que no exista prejuicio hacia las otras áreas del sistema de salud, dado el costo elevado de las nuevas tecnologías.

Cost-effective analysis of different algorithms for the diagnosis of hepatitis C virus infection

We compared the cost-benefit of two algorithms, recently proposed by the Centers for Disease Control and Prevention, USA, with the conventional one, the most appropriate for the diagnosis of hepatitis C virus (HCV) infection in the Brazilian population. Serum samples were obtained from 517 ELISA-positive or -inconclusive blood donors who had returned to Fundação Pró-Sangue/Hemocentro de São Paulo to confirm previous results. Algorithm A was based on signal-to-cut-off (s/co) ratio of ELISA anti-HCV samples that show s/co ratio ≥95 percent concordance with immunoblot (IB) positivity. For algorithm B, reflex nucleic acid amplification testing by PCR was required for ELISA-positive or -inconclusive samples and IB for PCR-negative samples. For algorithm C, all positive or inconclusive ELISA samples were submitted to IB. We observed a similar rate of positive results with the three algorithms: 287, 287, and 285 for A, B, and C, respectively, and 283 were concordant with one another. Indeterminate results from algorithms A and C were elucidated by PCR (expanded algorithm) which detected two more positive samples. The estimated cost of algorithms A and B was US$21,299.39 and US$32,397.40, respectively, which were 43.5 and 14.0 percent more economic than C (US$37,673.79). The cost can vary according to the technique used. We conclude that both algorithms A and B are suitable for diagnosing HCV infection in the Brazilian population. Furthermore, algorithm A is the more practical and economical one since it requires supplemental tests for only 54 percent of the samples. Algorithm B provides early information about the presence of viremia.