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

NAVIGATORE-Lombardia Study Group

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Hepatology
DOIs
Publication statusE-pub ahead of print - Nov 23 2018

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Chronic Hepatitis C
Hepacivirus
Safety
Genotype
RNA
Fibrosis
Therapeutics
Liver
Coinfection
Glomerular Filtration Rate
Platelet Count
Chronic Renal Insufficiency
Pharmaceutical Preparations
Interferons
Italy
HIV Infections
Albumins
Body Mass Index
Clinical Trials
Recurrence

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Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C. / NAVIGATORE-Lombardia Study Group.

In: Journal of Hepatology, 23.11.2018.

Research output: Contribution to journalArticle

@article{65d064ccd69f40adb9b83124eb1b0750,
title = "Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C",
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.",
author = "{NAVIGATORE-Lombardia Study Group} and Roberta D'Ambrosio and Luisa Pasulo and Massimo Puoti and Maria Vinci and Monica Schiavini and Sergio Lazzaroni and Alessandro Soria and Federico Gatti and Barbara Menzaghi and Alessio Aghemo and Francesca Capelli and Rumi, {Maria Grazia} and Lorenzo Morini and Alessia Giorgini and Pigozzi, {Marie Graciella} and Angelo Rossini and Franco Maggiolo and Angelo Pan and Massimo Memoli and Ombretta Spinelli and {Del Poggio}, Paolo and Valeria Saladino and Angiola Spinetti and {De Bona}, Anna and Andrea Capretti and Caterina Uberti-Foppa and Paolo Bonfanti and Natalia Terreni and Fernanda Menozzi and Colombo, {Alberto Eraldo} and Omar Giglio and Riccardo Centenaro and Marta Borghi and Chiara Baiguera and Viviana Picciotto and Simona Landonio and Andrea Gori and Carlo Magnani and Franco Noventa and Stefania Paolucci and Pietro Lampertico and Stefano Fagiuoli",
note = "Copyright {\circledC} 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.",
year = "2018",
month = "11",
day = "23",
doi = "10.1016/j.jhep.2018.11.011",
language = "English",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Real-world effectiveness and safety of glecaprevir/pibrentasvir in 723 patients with chronic hepatitis C

AU - NAVIGATORE-Lombardia Study Group

AU - D'Ambrosio, Roberta

AU - Pasulo, Luisa

AU - Puoti, Massimo

AU - Vinci, Maria

AU - Schiavini, Monica

AU - Lazzaroni, Sergio

AU - Soria, Alessandro

AU - Gatti, Federico

AU - Menzaghi, Barbara

AU - Aghemo, Alessio

AU - Capelli, Francesca

AU - Rumi, Maria Grazia

AU - Morini, Lorenzo

AU - Giorgini, Alessia

AU - Pigozzi, Marie Graciella

AU - Rossini, Angelo

AU - Maggiolo, Franco

AU - Pan, Angelo

AU - Memoli, Massimo

AU - Spinelli, Ombretta

AU - Del Poggio, Paolo

AU - Saladino, Valeria

AU - Spinetti, Angiola

AU - De Bona, Anna

AU - Capretti, Andrea

AU - Uberti-Foppa, Caterina

AU - Bonfanti, Paolo

AU - Terreni, Natalia

AU - Menozzi, Fernanda

AU - Colombo, Alberto Eraldo

AU - Giglio, Omar

AU - Centenaro, Riccardo

AU - Borghi, Marta

AU - Baiguera, Chiara

AU - Picciotto, Viviana

AU - Landonio, Simona

AU - Gori, Andrea

AU - Magnani, Carlo

AU - Noventa, Franco

AU - Paolucci, Stefania

AU - Lampertico, Pietro

AU - Fagiuoli, Stefano

N1 - Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

PY - 2018/11/23

Y1 - 2018/11/23

N2 - 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.

AB - 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.

U2 - 10.1016/j.jhep.2018.11.011

DO - 10.1016/j.jhep.2018.11.011

M3 - Article

C2 - 30472321

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

ER -