Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease.
(2017) Liver International — Vol. 37, n° 9, p. 1304-1313 (2017)
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Hézode, Christophe 
- 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT02268864.
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Citations
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 (Original work published 2017)