Ashley Brown, Piero Luigi Almasio, Lawrence Serfaty, Suzanne Bourgeois, Giovanni Battista Gaeta, Peter Buggisch, Moisés Diago, Ramon Planas, Stefan Zeuzem, Ferenc Szalay, Edmund Omoruyi, I. Lonjon-Domanec, Christophe Hézode, M. Schlag, Y. Horsmans, Ralph DeMasi, Hã©zode, Christophe, Almasio, Piero L., Bourgeois, Stefan, Buggisch, Peter, Brown, Ashley, Diago, Moise, Horsmans, Yve, Serfaty, Lawrence, Szalay, Ferenc, Gaeta, Giovanni B., Planas, Ramon, Schlag, Michael, Lonjon-Domanec, Isabelle, Omoruyi, Edmund, Demasi, Ralph, Zeuzem, Stefan, Hezode 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., and Zeuzem S.
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≥18years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150mg)+daclatasvir (60mg) once daily was administered for 12 or 24weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12weeks after the end of treatment. Results: A total of 106 patients were treated; 27% patients were aged >65years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12weeks of treatment and 64/106 received 24weeks 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.