title: Randomized comparison of daclatasvir + asunaprevir versus telaprevir + peginterferon/ribavirin in Japanese hepatitis C virus patients.
abstract: OBJECTIVE
  Daclatasvir combined with asunaprevir is the first all-oral, ribavirin-free treatment of hepatitis C virus genotype 1b infection in Japan. This study compared the efficacy and safety of daclatasvir plus asunaprevir versus telaprevir plus peginterferon/ribavirin in Japanese treatment-naive patients infected with hepatitis C virus genotype 1b.
  
  
  METHODS
  Treatment-naive patients (20-70 years; baseline viral load, ≥ 100,000 IU/mL) were randomly assigned (stratified by IL28B rs8099917 TT/non-TT status) to receive either daclatasvir 60 mg tablets once daily and asunaprevir 100 mg softgel capsules twice daily for 24 weeks or telaprevir 750 mg (3 × 250 mg tablets) three times daily for 12 weeks and peginterferon/ribavirin per Japanese prescribing information for 24 weeks. A cohort of prior relapsers to peginterferon/ribavirin (20-75 years; baseline viral load, ≥ 100,000 IU/mL) received daclatasvir plus asunaprevir.
  
  
  RESULTS
  In treatment-naive patients, sustained virologic response at post-treatment week 12 in daclatasvir plus asunaprevir recipients was non-inferior (treatment difference, +25.8% in favor of daclatasvir plus asunaprevir) and higher (89.1%, 106/119) than telaprevir plus peginterferon/ribavirin recipients (62.2%, 69/111); sustained viral response was achieved in 95.5% (n = 21/22) of relapsers. Numerically, fewer patients receiving daclatasvir plus asunaprevir compared with telaprevir plus peginterferon/ribavirin experienced serious adverse events (4.2% vs. 5.4%), adverse events leading to discontinuation of any drug (5.0% vs. 62.2%), grade 3/4 treatment-related adverse events (14.3% vs. 72.1%), rash-related events (0% vs. 13.5%), or anemia (0% vs. 47.7%).
  
  
  CONCLUSIONS
  Marked differences were observed in the efficacy and safety profile of daclatasvir in combination with asunaprevir, compared with telaprevir plus peginterferon/ribavirin.
authors.affiliation: Toranomon Hospital.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: Toranomon Hospital.
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Suzuki
authors.affiliation: Toranomon Hospital.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Sapporo-Kosei General Hospital, Sapporo.
authors.forename: Joji
authors.initials: J
authors.lastname: Toyota
authors.affiliation: Sapporo-Kosei General Hospital, Sapporo.
authors.forename: Yoshiyasu
authors.initials: Y
authors.lastname: Karino
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chayama
authors.affiliation: Hiroshima University, Hiroshima.
authors.forename: Yoshiiku
authors.initials: Y
authors.lastname: Kawakami
authors.affiliation: Kumamoto Shinto General Hospital, Kumamoto.
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Fujiyama
authors.affiliation: Showa University Koto Toyosu Hospital.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Ito
authors.affiliation: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Bristol-Myers KK, Tokyo, and.|Hiroshima University, Hiroshima.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Tamura
authors.affiliation: Bristol-Myers KK, Tokyo, and.|Hiroshima University, Hiroshima.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Ueki
authors.affiliation: Bristol-Myers KK, Tokyo, and.|Hiroshima University, Hiroshima.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishikawa
authors.affiliation: Bristol-Myers KK, Tokyo, and.|Hiroshima University, Hiroshima.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Hu
authors.affiliation: Bristol Myers Squibb Research and Development, Princeton, New Jersey, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: McPhee
authors.affiliation: Bristol Myers Squibb Research and Development, Princeton, New Jersey, USA.
authors.forename: Misti
authors.initials: M
authors.lastname: Linaberry
authors.affiliation: Bristol Myers Squibb Research and Development, Princeton, New Jersey, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Hughes
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D044466:Asian People; D002219:Carbamates; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D006526:Hepatitis C / Q000188:drug therapy*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D007546:Isoquinolines / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011759:Pyrrolidines; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage*; D013449:Sulfonamides / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000031:analogs & derivatives; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D002219:Carbamates; D007093:Imidazoles; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007546:Isoquinolines; D009842:Oligopeptides; D011759:Pyrrolidines; D011994:Recombinant Proteins; D013449:Sulfonamides; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir; C417083:peginterferon alfa-2b; D014633:Valine; C549273:daclatasvir; C100416:peginterferon alfa-2a; C571889:asunaprevir
keywords: asunaprevir; daclatasvir; efficacy; hepatitis C; safety