title: Effectiveness of triple therapy with simeprevir for chronic hepatitis C genotype 1b patients with prior telaprevir failure.
abstract: Favourable efficacy and safety profiles for simeprevir in combination with pegylated interferon alpha (PEG-IFNα) and ribavirin (triple therapy) have been shown in clinical trials. This study was carried out to evaluate the effectiveness of simeprevir-based triple therapy for patients with prior telaprevir treatment failure. This multicentre, observational cohort consisted of 345 consecutive Japanese patients infected with HCV genotype 1b, including 20 who had experienced telaprevir-based triple therapy. Amino acid substitutions in the NS3/4A region were identified by direct sequencing at the time of relapse or breakthrough in treatment with telaprevir and at the initiation of treatment with simeprevir. Patients were stratified according to prior response to PEG-IFNα and ribavirin. Of the 20 patients with telaprevir treatment failure, 10 (50.0%) achieved sustained virological response at week 12 after the end of treatment (SVR12). For patients treatment naïve [3/4 (75.0%)] or with prior relapse [1/1 (100%)] or partial response [5/6 (83.3%)] to PEG-IFNα and ribavirin, almost all achieved SVR12, mainly because of the improvement of treatment adherence, especially to direct-acting antiviral agent and ribavirin. However, of the nine patients with prior null response to PEG-IFNα and ribavirin, only one (11.1%) achieved SVR12, despite all having received an adequate treatment dosage, and five (55.6%) achieved rapid virological response. The treatment outcome of simeprevir-based triple therapy for HCV genotype 1b patients with prior telaprevir failure depended on the prior response to PEG-IFNα and ribavirin. For patients with prior null response to PEG-IFNα and ribavirin, retreatment with simeprevir-based triple therapy is not a useful option.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Ogawa
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Furusyo
authors.affiliation: Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Dohmen
authors.affiliation: Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Kajiwara
authors.affiliation: Department of Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Kawano
authors.affiliation: The Center for Liver Disease, Shin-Kokura Hospital, Kitakyushu, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Nomura
authors.affiliation: Department of Medicine, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Satoh
authors.affiliation: Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakamuta
authors.affiliation: Department of Medicine, Fukuoka City Hospital, Fukuoka, Japan.
authors.forename: T
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: K
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: S
authors.initials: S
authors.lastname: Shimoda
authors.affiliation: Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use; D002352:Carrier Proteins / Q000235:genetics; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D047908:Intracellular Signaling Peptides and Proteins; D007564:Japan; D008103:Liver Cirrhosis / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D000069616:Simeprevir / Q000009:adverse effects / Q000627:therapeutic use*; D017211:Treatment Failure; D017361:Viral Nonstructural Proteins / Q000235:genetics; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000998:Antiviral Agents; D002352:Carrier Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D047908:Intracellular Signaling Peptides and Proteins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D000069616:Simeprevir; D017361:Viral Nonstructural Proteins; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C455041:NS4A cofactor peptide, Hepatitis C virus; C486464:telaprevir; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
keywords: hepatitis C virus; pegylated interferon; ribavirin; simeprevir; telaprevir