Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease

Christophe Hézode, Piero L. Almasio, Stefan Bourgeois, Peter Buggisch, Ashley Brown, Moises Diago, Yves Horsmans, Lawrence Serfaty, F. Szalay, Giovanni B. Gaeta, Ramon Planas, Michael Schlag, Isabelle Lonjon-Domanec, Edmund Omoruyi, Ralph DeMasi, Stefan Zeuzem

Research output: Article

4 Citations (Scopus)

Abstract

Background & Aims: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naïve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. Methods: This phase II, open-label, single-arm, multicentre study included patients aged ≥18 years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150 mg)+daclatasvir (60 mg) once daily was administered for 12 or 24 weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12 weeks after the end of treatment. Results: A total of 106 patients were treated; 27% patients were aged >65 years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89 mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12 weeks of treatment and 64/106 received 24 weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had ≥1 adverse event during treatment, including six (6%) patients with ≥1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. Conclusions: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.

Original languageEnglish
Pages (from-to)1304-1313
Number of pages10
JournalLiver International
Volume37
Issue number9
DOIs
Publication statusPublished - szept. 1 2017

Fingerprint

Hepacivirus
Liver Diseases
Genotype
Therapeutics
Fibrosis
Simeprevir
BMS-790052
Virus Diseases
Glomerular Filtration Rate
Multicenter Studies
Antiviral Agents
Comorbidity
Hypertension
Safety
Recurrence

ASJC Scopus subject areas

  • Hepatology

Cite this

Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease. / Hézode, Christophe; Almasio, Piero L.; Bourgeois, Stefan; Buggisch, Peter; Brown, Ashley; Diago, Moises; Horsmans, Yves; Serfaty, Lawrence; Szalay, F.; Gaeta, Giovanni B.; Planas, Ramon; Schlag, Michael; Lonjon-Domanec, Isabelle; Omoruyi, Edmund; DeMasi, Ralph; Zeuzem, Stefan.

In: Liver International, Vol. 37, No. 9, 01.09.2017, p. 1304-1313.

Research output: Article

Hézode, C, Almasio, PL, Bourgeois, S, Buggisch, P, Brown, A, Diago, M, Horsmans, Y, Serfaty, L, Szalay, F, Gaeta, GB, Planas, R, Schlag, M, Lonjon-Domanec, I, Omoruyi, E, DeMasi, R & Zeuzem, S 2017, 'Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease', Liver International, vol. 37, no. 9, pp. 1304-1313. https://doi.org/10.1111/liv.13376
Hézode, Christophe ; Almasio, Piero L. ; Bourgeois, Stefan ; Buggisch, Peter ; Brown, Ashley ; Diago, Moises ; Horsmans, Yves ; Serfaty, Lawrence ; Szalay, F. ; Gaeta, Giovanni B. ; Planas, Ramon ; Schlag, Michael ; Lonjon-Domanec, Isabelle ; Omoruyi, Edmund ; DeMasi, Ralph ; Zeuzem, Stefan. / Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease. In: Liver International. 2017 ; Vol. 37, No. 9. pp. 1304-1313.
@article{3dcbea26ba3e48ab960b73371fbb3713,
title = "Simeprevir and daclatasvir for 12 or 24 weeks in treatment-na{\"i}ve patients with hepatitis C virus genotype 1b and advanced liver disease",
abstract = "Background & Aims: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-na{\"i}ve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. Methods: This phase II, open-label, single-arm, multicentre study included patients aged ≥18 years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150 mg)+daclatasvir (60 mg) once daily was administered for 12 or 24 weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12 weeks after the end of treatment. Results: A total of 106 patients were treated; 27{\%} patients were aged >65 years, 39{\%} had cirrhosis, 53{\%} had estimated glomerular filtration rate 30-89 mL/min, 14{\%} had diabetes, and 38{\%} had arterial hypertension. Overall, 42/106 received 12 weeks of treatment and 64/106 received 24 weeks of treatment. Ninety-seven (92{\%}) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70{\%}) patients had ≥1 adverse event during treatment, including six (6{\%}) patients with ≥1 serious adverse event. Three (3{\%}) patients discontinued treatment owing to adverse events. Conclusions: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.",
keywords = "daclatasvir, genotype 1b, hepatitis C virus, resistance-associated substitutions, simeprevir",
author = "Christophe H{\'e}zode and Almasio, {Piero L.} and Stefan Bourgeois and Peter Buggisch and Ashley Brown and Moises Diago and Yves Horsmans and Lawrence Serfaty and F. Szalay and Gaeta, {Giovanni B.} and Ramon Planas and Michael Schlag and Isabelle Lonjon-Domanec and Edmund Omoruyi and Ralph DeMasi and Stefan Zeuzem",
year = "2017",
month = "9",
day = "1",
doi = "10.1111/liv.13376",
language = "English",
volume = "37",
pages = "1304--1313",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - Simeprevir and daclatasvir for 12 or 24 weeks in treatment-naïve patients with hepatitis C virus genotype 1b and advanced liver disease

AU - Hézode, Christophe

AU - Almasio, Piero L.

AU - Bourgeois, Stefan

AU - Buggisch, Peter

AU - Brown, Ashley

AU - Diago, Moises

AU - Horsmans, Yves

AU - Serfaty, Lawrence

AU - Szalay, F.

AU - Gaeta, Giovanni B.

AU - Planas, Ramon

AU - Schlag, Michael

AU - Lonjon-Domanec, Isabelle

AU - Omoruyi, Edmund

AU - DeMasi, Ralph

AU - Zeuzem, Stefan

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Background & Aims: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naïve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. Methods: This phase II, open-label, single-arm, multicentre study included patients aged ≥18 years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150 mg)+daclatasvir (60 mg) once daily was administered for 12 or 24 weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12 weeks after the end of treatment. Results: A total of 106 patients were treated; 27% patients were aged >65 years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89 mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12 weeks of treatment and 64/106 received 24 weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had ≥1 adverse event during treatment, including six (6%) patients with ≥1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. Conclusions: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.

AB - Background & Aims: We investigated the efficacy and safety of simeprevir plus daclatasvir in treatment-naïve patients with chronic, genotype 1b hepatitis C virus infection and advanced liver disease, excluding patients with pre-defined NS5A resistance-associated substitutions. Methods: This phase II, open-label, single-arm, multicentre study included patients aged ≥18 years with advanced fibrosis or compensated cirrhosis (METAVIR F3/4). Patients with NS5A-Y93H or L31M/V resistance-associated substitutions at screening were excluded. Simeprevir (150 mg)+daclatasvir (60 mg) once daily was administered for 12 or 24 weeks; treatment could be extended to 24 weeks prior to or at the Week 12 visit. Primary efficacy endpoint was sustained virological response 12 weeks after the end of treatment. Results: A total of 106 patients were treated; 27% patients were aged >65 years, 39% had cirrhosis, 53% had estimated glomerular filtration rate 30-89 mL/min, 14% had diabetes, and 38% had arterial hypertension. Overall, 42/106 received 12 weeks of treatment and 64/106 received 24 weeks of treatment. Ninety-seven (92%) patients achieved a sustained virological response 12 weeks after the end of treatment. The reasons for failure were viral breakthrough (n=7) at weeks 4-16, early treatment discontinuation (n=1) and viral relapse (n=1). Seventy-four (70%) patients had ≥1 adverse event during treatment, including six (6%) patients with ≥1 serious adverse event. Three (3%) patients discontinued treatment owing to adverse events. Conclusions: Simeprevir+daclatasvir demonstrated strong antiviral activity and was well-tolerated in patients with hepatitis C virus genotype 1b infection, advanced liver disease and a high prevalence of comorbidities. However, viral breakthrough occurred in seven patients, making this regimen unsatisfactory.

KW - daclatasvir

KW - genotype 1b

KW - hepatitis C virus

KW - resistance-associated substitutions

KW - simeprevir

UR - http://www.scopus.com/inward/record.url?scp=85017206443&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85017206443&partnerID=8YFLogxK

U2 - 10.1111/liv.13376

DO - 10.1111/liv.13376

M3 - Article

C2 - 28135777

AN - SCOPUS:85017206443

VL - 37

SP - 1304

EP - 1313

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 9

ER -