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

NAVIGATORE-Lombardia and Veneto Study Groups

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background & Aims: 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. 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.

Original languageEnglish
JournalJournal of Hepatology
DOIs
Publication statusAccepted/In press - Jan 1 2019

Fingerprint

Hepatitis C
Antiviral Agents
Safety
Fibrosis
Treatment Failure
Retreatment
RNA
Italy
Hepatocellular Carcinoma
velpatasvir
Sofosbuvir
Intention to Treat Analysis
Hyperbilirubinemia
Ribavirin
Virus Diseases
Hepacivirus
Fatigue
Anemia
Appointments and Schedules
Genotype

Keywords

  • Direct-acting antivirals
  • HCV
  • RAS
  • Resistance
  • Retreatment
  • Sofosbuvir

ASJC Scopus subject areas

  • Hepatology

Cite this

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

In: Journal of Hepatology, 01.01.2019.

Research output: Contribution to journalArticle

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title = "Real-life effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients with previous DAA failure",
abstract = "Background & Aims: 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. 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.",
keywords = "Direct-acting antivirals, HCV, RAS, Resistance, Retreatment, Sofosbuvir",
author = "{NAVIGATORE-Lombardia and Veneto Study Groups} and Elisabetta Degasperi and Angiola Spinetti and Andrea Lombardi and Simona Landonio and Rossi, {Maria Cristina} and Luisa Pasulo and Pietro Pozzoni and Alessia Giorgini and Paolo Fabris and Antonietta Romano and Lorenzo Lomonaco and Massimo Puoti and Maria Vinci and Federico Gatti and Giada Carolo and Alessia Zoncada and Paolo Bonfanti and Russo, {Francesco Paolo} and Alessio Aghemo and Alessandro Soria and Riccardo Centenaro and Franco Maggiolo and Pierangelo Rovere and Francesca Pasin and Veronica Paon and Giovanni Faggiano and Alessandro Vario and Glenda Grossi and Roberta Soffredini and Canio Carriero and Stefania Paolucci and Franco Noventa and Alfredo Alberti and Pietro Lampertico and Stefano Fagiuoli",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.jhep.2019.07.020",
language = "English",
journal = "Journal of Hepatology",
issn = "0168-8278",
publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Real-life effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir in hepatitis C patients with previous DAA failure

AU - NAVIGATORE-Lombardia and Veneto Study Groups

AU - Degasperi, Elisabetta

AU - Spinetti, Angiola

AU - Lombardi, Andrea

AU - Landonio, Simona

AU - Rossi, Maria Cristina

AU - Pasulo, Luisa

AU - Pozzoni, Pietro

AU - Giorgini, Alessia

AU - Fabris, Paolo

AU - Romano, Antonietta

AU - Lomonaco, Lorenzo

AU - Puoti, Massimo

AU - Vinci, Maria

AU - Gatti, Federico

AU - Carolo, Giada

AU - Zoncada, Alessia

AU - Bonfanti, Paolo

AU - Russo, Francesco Paolo

AU - Aghemo, Alessio

AU - Soria, Alessandro

AU - Centenaro, Riccardo

AU - Maggiolo, Franco

AU - Rovere, Pierangelo

AU - Pasin, Francesca

AU - Paon, Veronica

AU - Faggiano, Giovanni

AU - Vario, Alessandro

AU - Grossi, Glenda

AU - Soffredini, Roberta

AU - Carriero, Canio

AU - Paolucci, Stefania

AU - Noventa, Franco

AU - Alberti, Alfredo

AU - Lampertico, Pietro

AU - Fagiuoli, Stefano

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background & Aims: 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. 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.

AB - Background & Aims: 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. 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.

KW - Direct-acting antivirals

KW - HCV

KW - RAS

KW - Resistance

KW - Retreatment

KW - Sofosbuvir

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