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

• Published in: Liver international 2017-09, Vol.37 (9), p.1304
• Main Authors: Hezode, Christophe, Almasio, Piero L, Bourgeois, Stefan, Buggisch, Peter, Brown, Ashley, Diago, Moises, Horsmans, Yves, Serfaty, Lawrence, Szalay, Ferenc, Gaeta, Giovanni B, Planas, Ramon, Schlag, Michael, Lonjon-Domanec, Isabelle, Omoruyi, Edmund, DeMasi, Ralph, Zeuzem, Stefan
• Format: Article
• Language: English
• Subjects: Antiviral activity; Chronic infection; Cirrhosis; Diabetes mellitus; Disease resistance; Fibrosis; Genotype & phenotype; Glomerular filtration rate; Hepatitis; Hepatitis C; Hypertension; Liver; Liver cirrhosis; Liver diseases; Patients; Viruses
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.13376

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.