Evaluation of 8-week glecaprevir/pibrentasvir treatment in direct-acting antiviral-naïve noncirrhotic HCV genotype 1 and 2infected patients in a real-world setting in Japan

J Viral Hepat. 2019 Nov;26(11):1266-1275. doi: 10.1111/jvh.13170. Epub 2019 Aug 9.

Abstract

Based on high efficacy and safety demonstrated in clinical trials, treatment with glecaprevir/pibrentasvir (G/P) for 8 weeks is recommended for hepatitis C virus (HCV)-infected patients who are direct-acting antiviral (DAA) naïve, genotype 1 or 2, and noncirrhotic. The aim of this study was to validate real-world experience with 8-week G/P treatment in Japan. We conducted a prospective observational cohort study in 554 patients who underwent 8-week treatment from among 1,022 patients who initiated G/P therapy. The majority (54.5%) were male, with a median age of 66 years, and HCV genotype distribution was genotype 1, 43.8%; genotype 2, 55.3%; and mixed subtype, 0.9%. Overall, the sustained virologic response rate at 12 weeks (SVR12) was 92.8% (530/571) in the intention-to-treat population and 99.3% (526/530) in the per-protocol population. The SVR12 rates by subgroups were as follows: subtype 1a, 100% (6/6); 1b, 100% (189/189); 2a, 99.3% (150/151); 2b, 99.0% (103/104); and mixed subtype, 50% (2/4). Among four patients with virologic failure following 8-week treatment with G/P, none had baseline polymorphisms or treatment-emergent amino acid substitutions in NS3. However, 2 of 4 patients with virologic failure had treatment-emergent amino acid substitutions in NS5A. Adverse events (AEs) were reported in 21.5% of patients and 1.2% of patients discontinued due to drug-related AEs. In conclusion, G/P treatment for 8 weeks was safe and effective for DAA-naïve noncirrhotic genotype 1 or 2 patients in a real-world clinical setting in Japan.

Keywords: glecaprevir; hepatitis C virus; pibrentasvir; real world; sustained virologic response.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aminoisobutyric Acids
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use
  • Cyclopropanes
  • Drug Therapy, Combination
  • Female
  • Genotype*
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics*
  • Hepatitis C / diagnosis
  • Hepatitis C / drug therapy*
  • Hepatitis C / virology*
  • Humans
  • Japan
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Pyrrolidines
  • Quinoxalines / therapeutic use
  • Sequence Analysis, DNA
  • Sulfonamides / therapeutic use
  • Sustained Virologic Response
  • Treatment Failure
  • Treatment Outcome
  • Young Adult

Substances

  • Aminoisobutyric Acids
  • Antiviral Agents
  • Benzimidazoles
  • Cyclopropanes
  • Lactams, Macrocyclic
  • Pyrrolidines
  • Quinoxalines
  • Sulfonamides
  • pibrentasvir
  • Proline
  • Leucine
  • glecaprevir