RESUMO
INTRODUCTION & AIM: Faldaprevir is a potent once-daily (q.d.) hepatitis C virus (HCV) NS3/4A protease inhibitor. The STARTVerso1 and STARTVerso2 phase 3 studies evaluated faldaprevir plus peginterferon alfa-2a/ribavirin (PegIFN/RBV) in treatment-naïve patients with chronic HCV genotype-1 infection. MATERIAL AND METHODS: Patients were randomized 1:2:2 to receive placebo, faldaprevir 120 mg q.d. (12 or 24 weeks) or faldaprevir 240 mg q.d. (12 weeks) all with PegIFN/RBV (24-48 weeks). Faldaprevir 120 mg for 12 weeks only (STARTVerso1 only) required early treatment success (ETS, HCV RNA < 25 IU/mL at week 4 and undetected at week 8). All faldaprevir-treated patients with ETS stopped PegIFN/RBV at week 24. Primary endpoint: sustained virologic response 12 weeks post-treatment (SVR12). RESULTS: SVR12 rates were significantly higher for patients treated with faldaprevir 120 or 240 mg (72% and 73%, respectively) compared with placebo (50%); estimated differences (adjusted for trial, race, and genotype-1 subtype) faldaprevir 120 mg 24% (95% CI: 17-31%, P < 0.0001), faldaprevir 240 mg 23% (95% CI: 16-30%, P < 0.0001). Subgroup analyses consistently showed higher SVR12 rates for patients receiving faldaprevir compared with placebo. The incidence of adverse events (AEs) was similar in faldaprevir 120-mg and placebo groups and slightly higher in the faldaprevir 240-mg group. Serious Aes were reported in 6%, 7%, and 8% of patients in placebo, faldaprevir 120-mg, and faldaprevir 240-mg groups, respectively. CONCLUSION: Addition of faldaprevir to PegIFN/RBV increased SVR12 in patients with HCV genotype-1, and was well tolerated. Faldaprevir 120 mg is effective in the treatment of HCV genotype-1. ClinicalTrials.gov: NCT01343888 and NCT01297270.
Assuntos
Antivirais/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Inibidores de Proteases/uso terapêutico , Ribavirina/uso terapêutico , Tiazóis/uso terapêutico , Adulto , Ácidos Aminoisobutíricos , Antivirais/efeitos adversos , Biomarcadores/sangue , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/metabolismo , Ensaios Clínicos Fase III como Assunto , Quimioterapia Combinada , Feminino , Genótipo , Hepacivirus/enzimologia , Hepacivirus/genética , Hepatite C/sangue , Hepatite C/diagnóstico , Humanos , Interferon-alfa/efeitos adversos , Interferon-alfa/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular , Leucina/análogos & derivados , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Oligopeptídeos/efeitos adversos , Polietilenoglicóis/efeitos adversos , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Inibidores de Proteases/efeitos adversos , Quinolinas , RNA Viral/sangue , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ribavirina/efeitos adversos , Tiazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Carga Viral , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/metabolismoRESUMO
INTRODUCTION: Recurrence of hepatitis C virus (HCV) in hepatic allograft is a major concern after successful liver transplant (LTx). AIM: To examine the response rate to pegylated interferon (PEG-IFN) and ribavirin in post-LTx patients with HCV recurrence. PATIENTS AND METHODS: Between January 2003 and September 2006, 60 patients with biopsy proven HCV recurrence (46 males and 14 females) received PEG-IFN 2a (n = 40) or IFN 2b (n = 20) with ribavirin. All patients were followed until July 2007. RESULTS: Fourteen patients (23.3%) tolerated antiviral therapy for less than six months and 10 (16.7%) discontinued therapy between six and 11 months. PEG-IFN dose was reduced in 21 (35%) patients and ribavirin dose was reduced in 16 (26.7%) patients. Overall, 55% patients achieved end of treatment response (EOT) and 35% sustained virological response (SVR). Mean Hepatitis Activity Index and Fibrosis Score pre-therapy was 5.8 +/- 1.9 and 1.7 +/- 1.3 and post-therapy, it was 4.4 +/- 2.1 and 2.4 +/- 1.6, respectively. Overall, three yr patient and graft survival was 73.9% and 69.2%, respectively. The patients with SVR had significantly lower viral load compared with other groups (p = 0.028). CONCLUSION: PEG-IFN and ribavirin therapy achieved 55% EOT and 35% SVR; 60% patients tolerated therapy. Biochemical response was observed in all groups of patients irrespective of virological response.