Beclabuvir in combination with asunaprevir and daclatasvir for hepatitis C virus genotype 1 infection: A systematic review and meta-analysis

J Med Virol. 2018 May;90(5):907-918. doi: 10.1002/jmv.24947. Epub 2018 Feb 1.

Abstract

Daclatasvir, asunaprevir (ASV), and beclabuvir (BCV) are direct-acting antivirals (DAAs) for patients with hepatitis C virus genotype 1 infection. This systematic review and meta-analysis investigating the efficacy and safety of this three-drug combination in HCV genotype 1 infection. Eleven electronic search engines were searched for relevant publications. Studies were screened for eligibility and data was extracted. The outcomes were pooled as event rate and risk ratio (RR). The protocol was registered in PROSPERO (CRD42017054391). Among the included six studies, five studies were included for the meta-analysis (n = 1261). The three-drug combination showed a high response rate in naïve patients with sustained virologic response at week-12 posttreatment (SVR12 ) rate = 95.7% (95%CI [93.8-97.1]) and no difference detected by adding ribavirin (RBV) (the pooled RR = 0.98, 95%CI [0.90-1.08], P = 0.70) or comparing with interferon-experienced patients (RR = 1.02, 95%CI [0.98-1.07], P = 0.31) regardless the genotype 1 subtypes or IL28B genotype. Treatment failure was minimal and showed no difference regarding the previous comparisons. Increasing the dose or the duration did not show a significant increase in the efficacy. In conclusion, this analysis showed high response rates in HCV genotype 1-infected patients treated with daclatasvir, ASV, and BCV irrespective of RBV use, prior interferon-based therapy, or restriction on non-cirrhotic patients, IL28B genotype, or baseline resistance-associated variants.

Keywords: antiviral agents; combination therapy; hepatitis C virus.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / adverse effects
  • Benzazepines / administration & dosage*
  • Benzazepines / adverse effects
  • Carbamates
  • Drug Therapy, Combination / adverse effects
  • Drug Therapy, Combination / methods
  • Drug-Related Side Effects and Adverse Reactions / epidemiology
  • Drug-Related Side Effects and Adverse Reactions / pathology
  • Genotype
  • Hepacivirus / classification
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology*
  • Humans
  • Imidazoles / administration & dosage*
  • Imidazoles / adverse effects
  • Indoles / administration & dosage*
  • Indoles / adverse effects
  • Isoquinolines / administration & dosage*
  • Isoquinolines / adverse effects
  • Pyrrolidines
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Sustained Virologic Response
  • Treatment Outcome
  • Valine / analogs & derivatives

Substances

  • 8-cyclohexyl-N-((dimethylamino)sulfonyl)-1,1a,2,12b-tetrahydro-11-methoxy-1a-((3-methyl-3,8-diazabicyclo(3.2.1)oct-8-yl)carbonyl)cycloprop(d)indolo(2,1-a)(2)benzazepine-5-carboxamide
  • Antiviral Agents
  • Benzazepines
  • Carbamates
  • Imidazoles
  • Indoles
  • Isoquinolines
  • Pyrrolidines
  • Sulfonamides
  • Valine
  • daclatasvir
  • asunaprevir