title: Efficacy of a 12-Week Simeprevir Plus Peginterferon/Ribavirin (PR) Regimen in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 4 (GT4) Infection and Mild-To-Moderate Fibrosis Displaying Early On-Treatment Virologic Response.
abstract: BACKGROUND
  HCV GT4 accounts for up to 20% of HCV infections worldwide. Simeprevir, given for 12 weeks as part of a 24- or 48-week combination regimen with PR is approved for the treatment of chronic HCV GT4 infection. Primary study objectives were assessment of efficacy and safety of simeprevir plus PR in treatment-naïve patients with HCV GT4 treated for 12 weeks. Primary efficacy outcome was sustained virologic response 12 weeks post-treatment (SVR12). Additional objectives included investigation of potential associations of rapid virologic response and baseline factors with SVR12.
  
  
  METHODS
  This multicentre, open-label, single-arm study (NCT01846832) evaluated efficacy and safety of simeprevir plus PR in 67 patients with HCV GT4 infection. Patients were treatment-naïve, aged 18-70 years with METAVIR F0-F2 fibrosis. Patients with early virologic response (HCV RNA <25 IU/mL [detectable/undetectable in IL28B CC patients or undetectable in IL28B CT/TT patients] at Week 2 and undetectable at Weeks 4 and 8) were eligible to stop all treatment at the end of Week 12, otherwise PR therapy was continued to Week 24.
  
  
  RESULTS
  Of 67 patients treated, 34 (51%) qualified for 12-week treatment including all but one patient with IL28B CC genotype (14/15). All patients in the 12-week group had undetectable HCV RNA at end of treatment, and 97% (33/34) achieved SVR12. No new safety signals with simeprevir plus PR were identified. The proportion of patients experiencing Grade 3-4 adverse events was lower in the 12-week group than in the 24-week group.
  
  
  CONCLUSIONS
  Our findings on simeprevir plus PR therapy shortened to 12 weeks in patients with HCV GT4 infection with favourable baseline characteristics and displaying early on-treatment virologic response are encouraging. No new safety signals were associated with simeprevir plus PR in this study.
  
  
  BACKGROUND
  NCT01846832.
authors.affiliation: Hepatology Department, Beaujon Hospital, University of Paris, Paris, France.
authors.forename: Tarik
authors.initials: T
authors.lastname: Asselah
authors.affiliation: CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.affiliation: Johann Wolfgang Goethe University Hospital, Medizinische Klinik 1, Frankfurt am Main, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Sarrazin
authors.affiliation: Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Gschwantler
authors.affiliation: Queen Mary Hospital, University of London, Barts Health, London, United Kingdom.
authors.forename: Graham R
authors.initials: GR
authors.lastname: Foster
authors.affiliation: Sezione di Gastroenterologia & Epatologia, Di.Bi.M.I.S., University of Palermo, Palermo, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Craxí
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: Division of Gastroenterology, Department of Medicine, King Abdulaziz Medical City, Jeddah, Saudi Arabia.
authors.forename: Faisal
authors.initials: F
authors.lastname: Sanai
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Ceyhun
authors.initials: C
authors.lastname: Bicer
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Oliver
authors.initials: O
authors.lastname: Lenz
authors.affiliation: Janssen Infectious Diseases BVBA, Beerse, Belgium.
authors.forename: Gino
authors.initials: G
authors.lastname: Van Dooren
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Nalpas
authors.affiliation: Janssen Pharmaceuticals, Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Lonjon-Domanec
authors.affiliation: Janssen-Cilag, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schlag
authors.affiliation: Liver Unit, Hospital Valle Hebron and Ciberehd del Institut Carlos III, Barcelona, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Buti
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000472:pathogenicity; D006526:Hepatitis C / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D000069616:Simeprevir / Q000009:adverse effects / Q000627:therapeutic use*; D019562:Viral Load; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D000069616:Simeprevir; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a