Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease.
Liver Int
; 37(9): 1304-1313, 2017 09.
Article
em En
| MEDLINE
| ID: mdl-28135777
ABSTRACT
BACKGROUND & AIMS:
We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naïve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions.METHODS:
This phase II, open-label, single-arm, multicentre study included patients aged ≥18 years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150 mg)+daclatasvir (60 mg) once daily was administered for 12 or 24 weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12 weeks after the end of treatment.RESULTS:
A total of 106 patients were treated; 27% patients were aged >65 years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89 mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12 weeks of treatment and 64/106 received 24 weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had ≥1 adverse event during treatment, including six (6%) patients with ≥1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events.CONCLUSIONS:
Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
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Hepatite C Crônica
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Simeprevir
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Imidazóis
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Cirrose Hepática
Tipo de estudo:
Clinical_trials
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Liver Int
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
França