title: Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, Université Paris-Est, Créteil, France.
authors.forename: Christophe
authors.identifier: 0000-0002-6762-8033
authors.initials: C
authors.lastname: Hézode
authors.affiliation: Gastroenterology and Hepatology Unit, Di.Bi.M.I.S, University of Palermo, Palermo, Italy.
authors.forename: Piero L
authors.initials: PL
authors.lastname: Almasio
authors.affiliation: Department of Gastroenterology and Hepatology, ZNA Campus Stuivenberg, Antwerp, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bourgeois
authors.affiliation: Institute for Interdisciplinary Medicine at the Asklepios Klinik St. Georg, Hamburg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Buggisch
authors.affiliation: Department of Hepatology, St Mary's Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Ashley
authors.initials: A
authors.lastname: Brown
authors.affiliation: Digestive Department, Valencia Hospital, Valencia, Spain.
authors.forename: Moises
authors.initials: M
authors.lastname: Diago
authors.affiliation: Department of Gastroenterology, Louvain Catholic University, Louvain, Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Horsmans
authors.affiliation: Department of Hepatology, Hôpital Saint-Antoine, Paris, France.
authors.forename: Lawrence
authors.initials: L
authors.lastname: Serfaty
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Szalay
authors.affiliation: Infectious Diseases, Department of Internal and Specialized Medicine, Second University of Naples, Naples, Italy.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Gaeta
authors.affiliation: Hepatology Unit Hospital Germans Trias I Pujol and CIBERehd, Badalona, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Planas
authors.affiliation: Janssen-Cilag, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlag
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Edmund
authors.initials: E
authors.lastname: Omoruyi
authors.affiliation: Janssen Research & Development LLC, Titusville, NJ, USA.
authors.forename: Ralph
authors.initials: R
authors.lastname: DeMasi
authors.affiliation: Department of Gastroenterology and Hepatology, J.W. Goethe University, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002219:Carbamates; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000821:virology*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011759:Pyrrolidines; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D000069616:Simeprevir / Q000008:administration & dosage / Q000627:therapeutic use*; D000072230:Sustained Virologic Response; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D011759:Pyrrolidines; D012367:RNA, Viral; D000069616:Simeprevir; D014633:Valine; C549273:daclatasvir
keywords: daclatasvir; genotype 1b; hepatitis C virus; resistance-associated substitutions; simeprevir