Safety and efficacy of glecaprevir/pibrentasvir in patients with chronic hepatitis C genotypes 1-6 receiving opioid substitution therapy.
Adult
Antiviral Agents
/ administration & dosage
Benzimidazoles
/ administration & dosage
Clinical Trials, Phase II as Topic
Clinical Trials, Phase III as Topic
Drug Combinations
Female
Genotype
Hepacivirus
/ genetics
Hepatitis C, Chronic
/ drug therapy
Humans
Male
Middle Aged
Opiate Substitution Treatment
/ methods
Pyrrolidines
/ administration & dosage
Quinoxalines
/ administration & dosage
Substance Abuse, Intravenous
/ rehabilitation
Sulfonamides
/ administration & dosage
Glecaprevir/pibrentasvir
Hepatitis C virus
Opioid substitution therapy
People who inject drugs
Journal
The International journal on drug policy
ISSN: 1873-4758
Titre abrégé: Int J Drug Policy
Pays: Netherlands
ID NLM: 9014759
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
19
06
2018
revised:
13
12
2018
accepted:
07
01
2019
pubmed:
9
2
2019
medline:
8
2
2020
entrez:
9
2
2019
Statut:
ppublish
Résumé
International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST. Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST. Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12. Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST.
Sections du résumé
BACKGROUND
International guidelines recommend treatment of hepatitis C virus (HCV) infection in people who inject drugs (PWID), including those on opioid substitution therapy (OST). The pangenotypic combination of glecaprevir and pibrentasvir has shown high sustained virologic response at post-treatment Week 12 (SVR12) in clinical trials. Herein, we evaluate the safety and efficacy of glecaprevir/pibrentasvir in patients receiving OST.
METHODS
Pooled data from patients with HCV genotypes 1-6 who were treated with glecaprevir/pibrentasvir for 8, 12, or 16 weeks in eight Phase 2 and 3 trials were categorized by use of OST. Treatment completion, treatment adherence, SVR12, adverse events (AEs), and laboratory abnormalities were evaluated for patients receiving and not receiving OST.
RESULTS
Among 2256 patients, 157 (7%) were receiving OST. Compared with patients not receiving OST, OST patients were younger (mean age, 46.8 vs 52.8 years), male (69% vs 54%), white (93% vs 80%), HCV treatment-naïve (86% vs 72%), had HCV genotype 3 (60% vs 26%), and had a history of depression or bipolar disorder (43% vs 19%). Most patients completed (OST: 98% [n/N = 154/157]; non-OST: 99% [n/N = 2070/2099]) and were adherent (received ≥90% of study drug doses) to glecaprevir/pibrentasvir treatment (OST: 98% [n/N = 121/123]; non-OST: 99% [n/N = 1884/1905] among patients with available data). In the intention-to-treat population, SVR12 rates in OST and non-OST patients were 96.2% (n/N = 151/157; 95% CI 93.2-99.2) and 97.9% (n/N = 2055/2099; 95% CI 97.3-98.5), respectively. For OST patients, reasons for nonresponse included virologic relapse (<1%; n = 1), premature study drug discontinuation (<1%; n = 1), and loss to follow-up (3%; n = 4). AEs occurring in ≥10% of OST patients were headache, fatigue, and nausea. Drug-related serious AEs, AEs leading to study drug discontinuation, and Grade 3 or higher laboratory abnormalities were infrequent in both groups (<1%). No HCV reinfections occurred through post-treatment Week 12.
CONCLUSION
Glecaprevir/pibrentasvir is highly efficacious and well tolerated in HCV-infected patients receiving OST.
Identifiants
pubmed: 30735896
pii: S0955-3959(19)30019-2
doi: 10.1016/j.drugpo.2019.01.011
pii:
doi:
Substances chimiques
Antiviral Agents
0
Benzimidazoles
0
Drug Combinations
0
Pyrrolidines
0
Quinoxalines
0
Sulfonamides
0
glecaprevir and pibrentasvir
0
Types de publication
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
73-79Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.