title: Comparative effectiveness and safety study of triple therapy with simeprevir or telaprevir for non-cirrhotic patients with chronic hepatitis C virus genotype 1b infection.
abstract: OBJECTIVE
  The addition of hepatitis C virus (HCV) NS3/4A protease inhibitors to pegylated-interferon alpha (PEG-IFNα) and ribavirin (triple therapy) has greatly improved treatment outcome. The aim of this study was to compare the effectiveness and safety of simeprevir-based or telaprevir-based triple therapy for non-cirrhotic patients in real-world clinical practice.
  
  
  METHODS
  This multicenter study consisted of 835 consecutive Japanese HCV genotype 1b patients treated in a clinical setting, 716 of whom were enrolled (simeprevir = 256 and telaprevir = 460). Logistic regression was carried out after propensity score matching to assess the sustained virological response at week 12 after the end of treatment (SVR12).
  
  
  RESULTS
  In the propensity-matched cohort (253 matched pairs), the SVR12 rates of the patients who underwent simeprevir-based or telaprevir-based triple therapy were 85.0% and 84.2%, respectively, by intention-to-treat analysis. Prior treatment response to PEG-IFNα/ribavirin and IL28B genotype was independently associated with SVR12 in both groups. No significant differences in the SVR12 rates stratified by prior treatment response to PEG-IFNα/ribavirin were found between the simeprevir (treatment-naïve 89.1%, prior relapse 94.3%, prior partial response 65.0%, and prior null response 33.3%) and telaprevir (treatment-naïve 87.8%, prior relapse 90.1%, prior partial response 68.4%, and prior null response 50.0%) groups. The incidence of adverse effects, such as anemia, severe rash, and the elevation of serum creatinine, was markedly higher in the telaprevir group.
  
  
  CONCLUSIONS
  Considering the effectiveness and safety, simeprevir-based triple therapy will continue to be a useful treatment option in Japan for treatment-naïve or prior relapse patients with a favorable IL28B genotype.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kajiwara
authors.affiliation: The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawano
authors.affiliation: Department of Medicine, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Dohmen
authors.affiliation: Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan.
authors.forename: Takeaki
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.affiliation: Department of Medicine, Fukuoka City Hospital, Fukuoka, Japan.
authors.forename: Toshimasa
authors.initials: T
authors.lastname: Koyanagi
authors.affiliation: Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.affiliation: Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.affiliation: Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage* / Q000009:adverse effects; D010597:Pharmacogenetics; D011092:Polyethylene Glycols / Q000008:administration & dosage; D057216:Propensity Score; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D000069616:Simeprevir / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011480:Protease Inhibitors; D011994:Recombinant Proteins; D012254:Ribavirin; D000069616:Simeprevir; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C486464:telaprevir; C100416:peginterferon alfa-2a
keywords: adverse effect; hepatitis C virus; pegylated interferon; simeprevir; telaprevir