Tratamento da HVC - Opções atuais e futuras
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O documento apresenta um resumo de uma palestra sobre o tratamento da hepatite C realizada pelo Dr. Alexandre Naime Barbosa. O documento inclui informações sobre os patrocínios recebidos pelo Dr. Barbosa, protocolos de tratamento para diferentes populações, diretrizes clínicas e opções de tratamento futuras.
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Tratamento da HVC - Opções atuais e futuras
- 1. Alexandre Naime Barbosa MD, PhD Professor Doutor - Infectologista Mesa Redonda: Tratamento da HVC 8º HEPATOAIDS Maio/2015 - São Paulo - SP
- 2. Declaro ter recebido incentivos na forma de inscrições de eventos científicos e/ou; viagens aéreas e terrestres e/ou; gastos com alimentação, hospedagem e translados e/ou; patrocínio para a realização de congressos; pagamentos por serviços prestados e/ou consultorias das seguintes empresas ou instituições nos últimos 12 meses: - Abbvie - FAMESP - Gilead - GSK-ViiV - Jansen - Ministério da Saúde - DDAHV - MSD - Prefeitura de Botucatu - SMS - Roche - Sociedade Paulista de Infectologia - UNESCO - UNESP www.drbarbosa.org
- 3. www.drbarbosa.org 1. Estudos Clínicos 1A. Virgens de Tratamento 1B. Populações Especiais 2. Guidelines e Protocolos 3. Opções Futuras 4. Considerações Finais
- 5. www.drbarbosa.org CCO Hepatitis - 2014 12 vs 24 wks : 95% no Total
- 6. www.drbarbosa.org CCO Hepatitis - 2014 93% no Total
- 7. www.drbarbosa.org SOF + RBV por 12 Semanas
- 8. www.drbarbosa.org CCO Hepatitis - 2014 GT2: 24/26 (92%)
- 10. www.drbarbosa.org CCO Hepatitis - 2014
- 14. www.drbarbosa.org CCO Hepatitis - 2014
- 15. www.drbarbosa.org CCO Hepatitis - 2015
- 17. www.drbarbosa.org CCO Hepatitis - 2015
- 18. www.drbarbosa.org CCO Hepatitis - 2015
- 19. www.drbarbosa.org CCO Hepatitis - 2015
- 21. www.drbarbosa.org Brasil /Ministério da Saúde/CONITEC - Simeprevir, sofosbuvir e daclatasvir no tratamento da hepatite crônica tipo C e coinfecções - 2015 AASLD/IDSA - Recommendations for Testing, Managing, and Treating Hepatitis C - 2014 EASL - Recommendations on Treatment of Hepatitis C - 2015
- 22. www.drbarbosa.org Brasil /Ministério da Saúde/CONITEC - Simeprevir, sofosbuvir e daclatasvir no tratamento da hepatite crônica tipo C e coinfecções - 2015 AASLD/IDSA - Recommendations for Testing, Managing, and Treating Hepatitis C - 2014 EASL - Recommendations on Treatment of Hepatitis C - 2015 Sem Cirrose Com Cirrose Experimentados 1ª: SOF + RBV (12 Sem) NR: A1 1ª: SOF + RBV (12 Sem) NR: A1 1ª: SOF + RBV (12 Sem) 2ª: SOF + DCV (24 Sem)
- 23. www.drbarbosa.org Brasil /Ministério da Saúde/CONITEC - Simeprevir, sofosbuvir e daclatasvir no tratamento da hepatite crônica tipo C e coinfecções - 2015 AASLD/IDSA - Recommendations for Testing, Managing, and Treating Hepatitis C - 2014 EASL - Recommendations on Treatment of Hepatitis C - 2015 Sem Cirrose Com Cirrose Experimentados 1ª: SOF + RBV (12 Sem) NR: A1 1ª: SOF + RBV (16 Sem) NR: C2 1ª: SOF + RBV (12 Sem) NR: A1 1ª: SOF + RBV (16-20 Sem) NR: B1 2ª: SOF + P/R (12 Sem)* NR: B1 3ª: SOF + DCV (12 Semᶧ) NR: B1 1ª: SOF + RBV (12 Sem) 2ª: SOF + DCV (24 Sem) 1ª: SOF + RBV (16-20 Sem)
- 24. www.drbarbosa.org Brasil /Ministério da Saúde/CONITEC - Simeprevir, sofosbuvir e daclatasvir no tratamento da hepatite crônica tipo C e coinfecções - 2015 AASLD/IDSA - Recommendations for Testing, Managing, and Treating Hepatitis C - 2014 EASL - Recommendations on Treatment of Hepatitis C - 2015 Sem Cirrose Com Cirrose Experimentados 1ª: SOF + RBV (12 Sem) NR: A1 1ª: SOF + RBV (16 Sem) NR: C2 1ª: SOF + RBV (12 - 16 Sem) NR: A1 2ª: SOF + P/R (12 Sem)* NR: B2 1ª: SOF + RBV (12 Sem) NR: A1 1ª: SOF + RBV (16-20 Sem) NR: B1 2ª: SOF + P/R (12 Sem)* NR: B1 3ª: SOF + DCV (12 Semᶧ) NR: B1 1ª: SOF + RBV (16-20 Sem) NR: B1 2ª: SOF + P/R (12 Sem)* NR: B1 3ª: SOF + DCV (12 Semᶧ) NR: B1 1ª: SOF + RBV (12 Sem) 2ª: SOF + DCV (24 Sem) 1ª: SOF + RBV (16-20 Sem) 1ª: SOF + RBV (16-20 Sem)
- 25. www.drbarbosa.org AASLD/IDSA - Recommendations for Testing, Managing, and Treating Hepatitis C - 2014 Não Recomendados Justificativa PEG-INF + RBV (24 Sem) Menor Eficácia (SOF + RBV) Monoterapias DAAs Menor Eficácia e Falhas BOC, TVP BOC (↓ Ação); TVP (EAs) LDV, SMP LDV (M31); SMP (↓ estudos)
- 27. www.drbarbosa.org GS-5816 Inibidor da NS5A GT 1-6, 1x/dia CCO Hepatitis - 2014
- 28. www.drbarbosa.org Gazoprevir: Inibidor da Protease NS3/NS4A Elbasvir: Inibidor da NS5A Pangenotípicos, coformulados CCO Hepatitis - 2015
- 30. 1. Virgens de Tratamento: A. SOF + RBV (12 Semanas) B. SOF + DCV (12 - 24 Semanas) 2. Experimentados/Cirrose: A. SOF + RBV (16-20 Sem) B. SOF + P/R (12 - 24 Sem) C. SOF + DCV (12 - 24 Sem) 3. Duração: Tempo ideal não está definido 4. Futuro: A. Estudos mais robustos B. ↑ Eficácia em Populações Especiais C. Drogas co-formuladas, 1 x/dia www.drbarbosa.org
Hinweis der Redaktion
- In the FISSION trial in treatment-naïve patients treated 12 weeks [25], the SVR rate was 95% (69/73). The response rate was better in patients without cirrhosis (97% vs. 83% in patients without and with cirrhosis, respectively). FISSION: Better Tolerability Profile With Sofosbuvir/RBV vs PegIFN/RBV Grade ≥ 3 AEs: 7% with SOF/RBV vs 19% for pegIFN/RBV Discontinuations due to AEs: 1% for SOF/RBV vs 11% for pegIFN/RBV
- The POSITRON trial included patients considered ineligible or intolerant to IFN, who were treated for 12 weeks with sofosbuvir and ribavirin [46]. SVR was achieved in 93% (101/109) of cases
- In the VALENCE trial [47], the SVR rates after 12 weeks of treatment were 97% (29/30) in treatment- naïve non-cirrhotic individuals, 100% (2/2) in treatmentnaïve cirrhotic patients, 91% (30/33) in treatment-experienced non-cirrhotic patients, and 88% (7/8) in treatment-experienced cirrhotic patients. In another study, 1 of 2 patients who relapsed after treatment with sofosbuvir and ribavirin retreated 24 weeks with sofosbuvir and ribavirin achieved an SVR [48].
- Outros esquemas de tratamento avaliados por meio de estudos de fase II com número menor de pacientes foram a associação entre sofosbuvir e daclatasvir (400 mg e 60 mg 1 vez ao dia) e de daclatasvir (60 mg 1 vez ao dia) com PEG-IFN/RBV. As taxas de RVS12 registradas para tratamentos com sofosbuvir e daclatasvir por 24 semanas foram de 86% (n=14) e 93% (n=14) para esquemas com e sem ribavirina em uma população mista de pacientes não tratados previamente e falhos de tratamento prévio com telaprevir [111]. Comments: Daclatasvir is active against genotype 2 in vitro. In a Phase II trial, 92% (24/26) of patients infected with genotype 2 achieved an SVR12 after 24 weeks of sofosbuvir and daclatasvir. Based on data with other, more difficult-to-cure HCV genotypes, 12 weeks is probably sufficient for this regimen that should be reserved for patients who failed with other options.
- High SVR12 rates were demonstrated in patients with HCV genotype 2 in whom prior treatment with PEGIFN and RBV failed who were retreated with 12 weeks of sofosbuvir plus RBV. Limited data are available for treatment-experienced patients with HCV genotype 2 infection and cirrhosis; however, in the FUSION study, numerically higher SVR12 rates were seen with extension of therapy from 12 weeks (60%) to 16 weeks (78%). (Jacobson, 2013b) In contrast, the VALENCE trial found high SVR12 rates among HCV genotype 2–infected persons with cirrhosis after only 12 weeks of sofosbuvir plus RBV (88%). (Zeuzem, 2013b) Thus, definitive recommendations on the appropriate duration of sofosbuvir and RBV for treatmentexperienced, HCV genotype 2–infected persons with cirrhosis cannot be made at this time. The decision to extend therapy to 16 weeks should be made on a case-by-case basis.
- High SVR12 rates were demonstrated in patients with HCV genotype 2 in whom prior treatment with PEGIFN and RBV failed who were retreated with 12 weeks of sofosbuvir plus RBV. Limited data are available for treatment-experienced patients with HCV genotype 2 infection and cirrhosis; however, in the FUSION study, numerically higher SVR12 rates were seen with extension of therapy from 12 weeks (60%) to 16 weeks (78%). (Jacobson, 2013b) In contrast, the VALENCE trial found high SVR12 rates among HCV genotype 2–infected persons with cirrhosis after only 12 weeks of sofosbuvir plus RBV (88%). (Zeuzem, 2013b) Thus, definitive recommendations on the appropriate duration of sofosbuvir and RBV for treatment experienced, HCV genotype 2–infected persons with cirrhosis cannot be made at this time. The decision to extend therapy to 16 weeks should be made on a case-by-case basis. In the VALENCE trial [47], the SVR rates after 12 weeks of treatment were 97% (29/30) in treatment- naïve non-cirrhotic individuals, 100% (2/2) in treatmentnaïve cirrhotic patients, 91% (30/33) in treatment-experienced non-cirrhotic patients, and 88% (7/8) in treatment-experienced cirrhotic patients. In another study, 1 of 2 patients who relapsed after treatment with sofosbuvir and ribavirin retreated 24 weeks with sofosbuvir and ribavirin achieved an SVR [48].
- Based on realworld data from Trio Health, lower response rates were seen in treatment-naive patients with cirrhosis than in those without cirrhosis. (Dieterich, 2014a) Although data to support extension of therapy are not yet available for treatment-naive patients with HCV genotype 2 infection, longer treatment duration improves SVR in treatment-experienced patients with cirrhosis. (Jacobson, 2013c) Owing to the small numbers of patients with HCV genotype 2 infection and cirrhosis enrolled in the registration trials, several phase IIIB studies are ongoing to specifically determine the appropriate length of treatment for this subgroup of patients (NCT01962441, NCT 02128542). Until these data are available, extending treatment from 12 weeks to 16 weeks in HCV genotype 2–infected patients with cirrhosis is recommended.
- Based on realworld data from Trio Health, lower response rates were seen in treatment-naive patients with cirrhosis than in those without cirrhosis. (Dieterich, 2014a) Although data to support extension of therapy are not yet available for treatment-naive patients with HCV genotype 2 infection, longer treatment duration improves SVR in treatment-experienced patients with cirrhosis. (Jacobson, 2013c) Owing to the small numbers of patients with HCV genotype 2 infection and cirrhosis enrolled in the registration trials, several phase IIIB studies are ongoing to specifically determine the appropriate length of treatment for this subgroup of patients (NCT01962441, NCT 02128542). Until these data are available, extending treatment from 12 weeks to 16 weeks in HCV genotype 2–infected patients with cirrhosis is recommended.
- In recognition of the potential limitations of sofosbuvir plus RBV in harder-to-treat, HCV genotype 2–infected patients with a prior treatment failure, particularly those with cirrhosis, combination therapy with PEG-IFN has been studied. The LONESTAR-2 trial (an open-label, single-site, single-arm, phase II trial) evaluated PEG-IFN (180 ?g weekly), sofosbuvir (400 mg daily), and weight-based RBV (1000 mg [<75 kg] to 1200 mg [?75 kg] daily in 2 divided doses for 12 weeks) in treatment-experienced patients with HCV genotype 2 or 3. (Lawitz, 2014a) Cirrhosis was present at baseline in 61% of patients. SVR12 was achieved in 22 of 23 (96%) persons with HCV genotype 2 infection. For patients with and without cirrhosis, SVR occurred in 13 of 14 (93%) and 9 of 9 (100%), respectively. Despite the limitations of this small study and accounting for the potential challenges inherent with IFN therapy, sofosbuvir plus PEG-IFN and RBV is an alternative 12-week regimen for HCV genotype 2–infected patients with cirrhosis. Comments: In the LONESTAR-2 Phase IIb study [49], a single centre study in which 23 treatment-experienced patients infected with HCV genotype 2, including 14 with cirrhosis, received 12 weeks of PegIFN-a, ribavirin and sofosbuvir, the SVR rate was 96%. In another study, 4/4 patients who relapsed after treatment with sofosbuvir and ribavirin retreated 12 weeks with the triple combination of PegIFN-a, ribavirin and sofosbuvir achieved an SVR [48].
- In another study, 4/4 patients who relapsed after treatment with sofosbuvir and ribavirin retreated 12 weeks with the triple combination of PegIFN-a, ribavirin and sofosbuvir achieved an SVR [48].
- Because of its poor activity in vitro and in vivo, boceprevir should not be used as therapy for patients with HCV genotype 2 infection. Although telaprevir plus PEG-IFN and RBV has antiviral activity against HCV genotype 2, (Foster, 2011) the additional adverse effects and longer duration of therapy required do not support use of this regimen. Similarly, although ledipasvir has adequate activity against HCV genotype 2, this is lost in the presence of the highly prevalent M31 polymorphism and thus is not recommended for treatment of HCV genotype 2 infection. (Nakamoto, 2014)