Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease

Christophe Hézode, Piero L. Almasio, Stefan Bourgeois, Peter Buggisch, Ashley Brown, Moises Diago, Yves Horsmans, Lawrence Serfaty, Ferenc Szalay, Giovanni B. Gaeta, Ramon Planas, Michael Schlag, Isabelle Lonjon-Domanec, Edmund Omoruyi, Ralph DeMasi, Stefan Zeuzem

Research output: Article

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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.

Original languageEnglish
Pages (from-to)1304-1313
Number of pages10
JournalLiver International
Volume37
Issue number9
DOIs
Publication statusPublished - szept. 2017

ASJC Scopus subject areas

  • Hepatology

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    Hézode, C., Almasio, P. L., Bourgeois, S., Buggisch, P., Brown, A., Diago, M., Horsmans, Y., Serfaty, L., Szalay, F., Gaeta, G. B., Planas, R., Schlag, M., Lonjon-Domanec, I., Omoruyi, E., DeMasi, R., & Zeuzem, S. (2017). Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease. Liver International, 37(9), 1304-1313. https://doi.org/10.1111/liv.13376