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
BACKGROUND AND AIMS: A single nucleotide polymorphism near the interleukin-28B (IL28B) gene has been shown to predict hepatitis C virus (HCV) treatment response. We aim to determine the role of the IL28B genotype in Asian patients. METHODS: A total of 118 patients (all Korean, 55 patients with genotype 1 infection and 63 patients with genotype 2 infection) were consecutively enrolled and analyzed. RESULTS: The sustained virological response (SVR) rate was 74% (87/118), while 26 patients (22%) relapsed and five patients were non-responders (4%). For rs8099917, the frequencies of major homozygotes (TT), heterozygotes (GT), and minor homozygotes (GG) were 0.85, 0.14 and 0.01, respectively. Of the 55 patients with HCV genotype 1 infection, the SVR rate was 67% and 44% (P = 0.19) and the non-response rate was 2% and 22% (P = 0.015) for the major allele and minor or hetero allele, respectively. Of the 63 patients with HCV genotype 2 infection, the SVR rate was 80% and 100% (P = 0.13) and the non-response rate was 4% and 0% (P = 0.55) for major allele and hetero allele, respectively. CONCLUSIONS: The IL28B genotype may help identify non-responding patients in HCV genotype 1, but not in HCV genotype 2. Because of the high frequency of favorable alleles and the low frequency of non-response, the IL28B polymorphism may play a smaller role in Asian patients.