Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C

J Hepatol. 2019 Mar;70(3):379-387. doi: 10.1016/j.jhep.2018.11.011. Epub 2018 Nov 23.

Abstract

Background and aims: The efficacy and safety of glecaprevir/pibrentasvir (G/P) for patients infected with hepatitis C virus (HCV) have only been investigated in clinical trials, with no real-world data currently available. The aim of our study was to investigate the effectiveness and safety of G/P in a real-world setting.

Methods: All patients with HCV consecutively starting G/P between October 2017 and January 2018 within the NAVIGATORE-Lombardia Network were analyzed. G/P was administered according to drug label (8, 12 or 16 weeks). Fibrosis was staged either histologically or by liver stiffness measurement. Sustained virological response (SVR) was defined as undetectable HCV-RNA 12 weeks after the end of treatment.

Results: A total of 723 patients (50% males) were treated with G/P, 89% for 8 weeks. The median age of our cohort was 58 years, with a median body mass index of 23.9 kg/m2, and median liver stiffness measurement of 6.1 kPa; 84% were F0-2 and 16% were interferon-experienced. Median HCV-RNA was 1,102,600 IU/ml, and 49% of patients had HCV genotype 1 (32% 1b), 28% genotype 2, 10% genotype 3 and 13% genotype 4. The median estimated glomerular filtration rate was 90.2 ml/min, platelet count 209x103/mm3 and albumin 4.3 g/dl. The SVR rates were 94% in intention-to-treat and 99.3% in per protocol analysis (8-week vs. 12 or 16-week: 99.2% vs. 100%). Five patients failed therapy because of post-treatment relapse; a post-treatment NS5A resistance-associated substitution was detected in 1 case. SVR rates were lower in males (p = 0.002) and in HCV genotype-3 (p = 0.046) patients treated for 8 weeks, but independent of treatment duration, fibrosis stage, baseline HCV-RNA, HIV co-infection, chronic kidney disease stage and viral kinetics. Mild adverse events were reported in 8.3% of the patients, and 0.7% of them prematurely withdrew treatment. Three patients died of drug-unrelated causes.

Conclusions: In a large real-world cohort of Italian patients, we confirmed the excellent effectiveness and safety of G/P administered for 8, 12 or 16 weeks.

Lay summary: A large number of patients with hepatitis C virus have been treated with glecaprevir/pibrentasvir (G/P) within the NAVIGATORE-Lombardia Network, in Italy. This is the first real-world study evaluating effectiveness and safety of G/P in patients with hepatitis C virus treated according to international recommendations. This study demonstrated excellent effectiveness (with sustained virological response rates of 99.3%) and safety profiles.

Keywords: DAA; Effectiveness; Glecaprevir; HCV; Pibrentasvir; RAS; Real-life; SVR; Safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoisobutyric Acids
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Benzimidazoles* / administration & dosage
  • Benzimidazoles* / adverse effects
  • Biopsy / methods
  • Cohort Studies
  • Cyclopropanes
  • Drug Combinations
  • Elasticity Imaging Techniques / methods
  • Female
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / diagnosis
  • Hepatitis C, Chronic* / drug therapy
  • Hepatitis C, Chronic* / epidemiology
  • Humans
  • Italy / epidemiology
  • Lactams, Macrocyclic
  • Leucine / analogs & derivatives
  • Liver / pathology*
  • Liver Cirrhosis / diagnosis
  • Liver Cirrhosis / etiology
  • Male
  • Middle Aged
  • Proline / analogs & derivatives
  • Pyrrolidines
  • Quinoxalines* / administration & dosage
  • Quinoxalines* / adverse effects
  • RNA, Viral / analysis
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / adverse effects
  • Sustained Virologic Response
  • Treatment Outcome

Substances

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