Randomized comparison of daclatasvir + asunaprevir versus telaprevir + peginterferon/ribavirin in Japanese hepatitis C virus patients

J Gastroenterol Hepatol. 2016 Jan;31(1):14-22. doi: 10.1111/jgh.13073.

Abstract

Background and aim: 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%).

Conclusion: Marked differences were observed in the efficacy and safety profile of daclatasvir in combination with asunaprevir, compared with telaprevir plus peginterferon/ribavirin.

Keywords: asunaprevir; daclatasvir; efficacy; hepatitis C; safety.

Publication types

  • Clinical Trial, Phase III
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage*
  • Asian People
  • Carbamates
  • Cohort Studies
  • Drug Therapy, Combination
  • Female
  • Hepatitis C / drug therapy*
  • Humans
  • Imidazoles / administration & dosage*
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage*
  • Isoquinolines / administration & dosage*
  • Male
  • Middle Aged
  • Oligopeptides / administration & dosage*
  • Polyethylene Glycols / administration & dosage*
  • Pyrrolidines
  • Recombinant Proteins / administration & dosage
  • Ribavirin / administration & dosage*
  • Sulfonamides / administration & dosage*
  • Treatment Outcome
  • Valine / analogs & derivatives
  • Young Adult

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Interferon alpha-2
  • Interferon-alpha
  • Isoquinolines
  • Oligopeptides
  • Pyrrolidines
  • Recombinant Proteins
  • Sulfonamides
  • Polyethylene Glycols
  • Ribavirin
  • telaprevir
  • peginterferon alfa-2b
  • Valine
  • daclatasvir
  • peginterferon alfa-2a
  • asunaprevir