Real-life effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients with previous DAA failure.

Antiviral Agents / administration & dosage Carbamates / administration & dosage Carcinoma, Hepatocellular / epidemiology Drug Combinations Drug Resistance, Viral Female Hepacivirus / drug effects Hepatitis C, Chronic / complications Heterocyclic Compounds, 4 or More Rings / administration & dosage Humans Italy / epidemiology Liver Cirrhosis / diagnosis Liver Neoplasms / epidemiology Macrocyclic Compounds / administration & dosage Male Middle Aged RNA, Viral / isolation & purification Retreatment / methods Risk Factors Sofosbuvir / administration & dosage Sulfonamides / administration & dosage Sustained Virologic Response Treatment Outcome Viral Nonstructural Proteins

Direct-acting antivirals HCV RAS Resistance Retreatment Sofosbuvir

Journal

Journal of hepatology

ISSN: 1600-0641

Titre abrégé: J Hepatol

Pays: Netherlands

ID NLM: 8503886

Informations de publication

Date de publication:
12 2019

Historique:

received: 28 02 2019

revised: 24 06 2019

accepted: 17 07 2019

pubmed: 23 8 2019

medline: 20 3 2021

entrez: 22 8 2019

Statut: ppublish

Résumé

Sofosbuvir/velpatasivr/voxilaprevir (SOF/VEL/VOX) is approved for retreatment of patients with HCV and a previous failure on direct-acting antivirals (DAAs), however real-life data are limited. The aim of this study was to assess the effectiveness and safety of SOF/VEL/VOX in a real-life setting. All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment. A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%). SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting. This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.

Sections du résumé

BACKGROUND & AIMS

METHODS

All consecutive patients with HCV receiving SOF/VEL/VOX between May-October 2018 in 27 centers in Northern Italy were enrolled. Bridging fibrosis (F3) and cirrhosis (F4) were diagnosed by liver stiffness measurement: >10 and >13 kPa respectively. Sustained virological response (SVR) was defined as undetectable HCV-RNA 4 (SVR4) or 12 (SVR12) weeks after the end-of-treatment.

RESULTS

A total of 179 patients were included: median age 57 (18-88) years, 74% males, median HCV-RNA 1,081,817 (482-25,590,000) IU/ml. Fibrosis stage was F0-F2 in 32%, F3 in 21%, F4 in 44%. HCV genotype was 1 in 58% (1b 33%, 1a 24%, 1nc 1%), 2 in 10%, 3 in 23% and 4 in 9%; 82% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Patients received SOF/VEL/VOX for 12 weeks, ribavirin was added in 22% of treatment schedules. Undetectable HCV-RNA was achieved by 74% of patients at week 4 and by 99% at week 12. Overall, 162/179 (91%) patients by intention to treat analysis and 162/169 (96%) by per protocol analysis achieved SVR12, respectively; treatment failures included 6 relapsers and 1 virological non-responder. Cirrhosis (p = 0.005) and hepatocellular carcinoma (p = 0.02) were the only predictors of treatment failure. Most frequent adverse events included fatigue (6%), hyperbilirubinemia (6%) and anemia (4%).

CONCLUSIONS

SOF/VEL/VOX is an effective and safe retreatment for patients with HCV who have failed on a previous DAA course in a real-life setting.

LAY SUMMARY

This is the largest European real-life study evaluating effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in a large cohort of consecutive patients with hepatitis C virus infection and a prior direct-acting antiviral failure, who were treated within the NAVIGATORE Lombardia and Veneto Networks, in Italy. This study demonstrated excellent effectiveness (98% and 96% sustained virological response rates at week 4 and 12, respectively) and an optimal safety profile of SOF/VEL/VOX. Cirrhosis and hepatocellular carcinoma onset were the only features associated with treatment failure.

Identifiants

DOI: 10.1016/j.jhep.2019.07.020 PMID: 31433303

pubmed: 31433303

pii: S0168-8278(19)30461-1

doi: 10.1016/j.jhep.2019.07.020

pii:

doi:

Substances chimiques

Antiviral Agents 0

Carbamates 0

Drug Combinations 0

Heterocyclic Compounds, 4 or More Rings 0

Macrocyclic Compounds 0

RNA, Viral 0

Sulfonamides 0

Viral Nonstructural Proteins 0

sofosbuvir velpatasvir voxilaprevir drug combination 0

Sofosbuvir WJ6CA3ZU8B

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

1106-1115