Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis

K. Rajender Reddy, Marc Bourlière, Mark Sulkowski, Masao Omata, Stefan Zeuzem, Jordan J. Feld, Eric Lawitz, Patrick Marcellin, Tania M. Welzel, Robert Hyland, Xiao Ding, Jenny Yang, Steven Knox, Phillip Pang, Hadas Dvory-Sobol, G. Mani Subramanian, William Symonds, John G. Mchutchison, Alessandra Mangia, Edward GaneMasashi Mizokami, Stanislas Pol, Nezam Afdhal

Research output: Contribution to journalArticle

177 Citations (Scopus)

Abstract

Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon-free regimens of direct-acting antiviral agents, making it difficult to optimize therapy. We performed a post-hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed-dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment-naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV-SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease-inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%-98%) achieved SVR12, 98% of treatment-naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV-SOF alone and 97% of those who received LDV-SOF plus RBV), although previously treated patients receiving 12 weeks of LDV-SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV-SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%-19%), and asthenia (14%-16%). One patient (

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalHepatology
Volume62
Issue number1
DOIs
Publication statusPublished - Jul 1 2015

Fingerprint

Virus Diseases
Hepacivirus
Fibrosis
Genotype
Safety
Ribavirin
Therapeutics
sofosbuvir drug combination ledipasvir
Clinical Trials
Asthenia
Protease Inhibitors
Interferons
Antiviral Agents
Fatigue
Headache
Confidence Intervals

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis : An integrated safety and efficacy analysis. / Reddy, K. Rajender; Bourlière, Marc; Sulkowski, Mark; Omata, Masao; Zeuzem, Stefan; Feld, Jordan J.; Lawitz, Eric; Marcellin, Patrick; Welzel, Tania M.; Hyland, Robert; Ding, Xiao; Yang, Jenny; Knox, Steven; Pang, Phillip; Dvory-Sobol, Hadas; Subramanian, G. Mani; Symonds, William; Mchutchison, John G.; Mangia, Alessandra; Gane, Edward; Mizokami, Masashi; Pol, Stanislas; Afdhal, Nezam.

In: Hepatology, Vol. 62, No. 1, 01.07.2015, p. 79-86.

Research output: Contribution to journalArticle

Reddy, KR, Bourlière, M, Sulkowski, M, Omata, M, Zeuzem, S, Feld, JJ, Lawitz, E, Marcellin, P, Welzel, TM, Hyland, R, Ding, X, Yang, J, Knox, S, Pang, P, Dvory-Sobol, H, Subramanian, GM, Symonds, W, Mchutchison, JG, Mangia, A, Gane, E, Mizokami, M, Pol, S & Afdhal, N 2015, 'Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis', Hepatology, vol. 62, no. 1, pp. 79-86. https://doi.org/10.1002/hep.27826
Reddy, K. Rajender ; Bourlière, Marc ; Sulkowski, Mark ; Omata, Masao ; Zeuzem, Stefan ; Feld, Jordan J. ; Lawitz, Eric ; Marcellin, Patrick ; Welzel, Tania M. ; Hyland, Robert ; Ding, Xiao ; Yang, Jenny ; Knox, Steven ; Pang, Phillip ; Dvory-Sobol, Hadas ; Subramanian, G. Mani ; Symonds, William ; Mchutchison, John G. ; Mangia, Alessandra ; Gane, Edward ; Mizokami, Masashi ; Pol, Stanislas ; Afdhal, Nezam. / Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis : An integrated safety and efficacy analysis. In: Hepatology. 2015 ; Vol. 62, No. 1. pp. 79-86.
@article{11ce600283f849c1bb55e2b849d2d1cc,
title = "Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis: An integrated safety and efficacy analysis",
abstract = "Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon-free regimens of direct-acting antiviral agents, making it difficult to optimize therapy. We performed a post-hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed-dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment-na{\"i}ve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV-SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69{\%} were previously treated and 47{\%} had failed previous treatment with a protease-inhibitor regimen. Overall, 493 patients (96{\%}; 95{\%} confidence interval [CI]: 94{\%}-98{\%}) achieved SVR12, 98{\%} of treatment-na{\"i}ve and 95{\%} of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95{\%} of patients receiving 12 weeks and 98{\%} of patients receiving 24 weeks of treatment), nor by addition of RBV (95{\%} of patients receiving LDV-SOF alone and 97{\%} of those who received LDV-SOF plus RBV), although previously treated patients receiving 12 weeks of LDV-SOF without RBV had an SVR12 rate of 90{\%}. One patient discontinued LDV-SOF because of an adverse event (AE). The most common AEs were headache (23{\%}), fatigue (16{\%}-19{\%}), and asthenia (14{\%}-16{\%}). One patient (",
author = "Reddy, {K. Rajender} and Marc Bourli{\`e}re and Mark Sulkowski and Masao Omata and Stefan Zeuzem and Feld, {Jordan J.} and Eric Lawitz and Patrick Marcellin and Welzel, {Tania M.} and Robert Hyland and Xiao Ding and Jenny Yang and Steven Knox and Phillip Pang and Hadas Dvory-Sobol and Subramanian, {G. Mani} and William Symonds and Mchutchison, {John G.} and Alessandra Mangia and Edward Gane and Masashi Mizokami and Stanislas Pol and Nezam Afdhal",
year = "2015",
month = "7",
day = "1",
doi = "10.1002/hep.27826",
language = "English",
volume = "62",
pages = "79--86",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Inc.",
number = "1",

}

TY - JOUR

T1 - Ledipasvir and sofosbuvir in patients with genotype 1 hepatitis C virus infection and compensated cirrhosis

T2 - An integrated safety and efficacy analysis

AU - Reddy, K. Rajender

AU - Bourlière, Marc

AU - Sulkowski, Mark

AU - Omata, Masao

AU - Zeuzem, Stefan

AU - Feld, Jordan J.

AU - Lawitz, Eric

AU - Marcellin, Patrick

AU - Welzel, Tania M.

AU - Hyland, Robert

AU - Ding, Xiao

AU - Yang, Jenny

AU - Knox, Steven

AU - Pang, Phillip

AU - Dvory-Sobol, Hadas

AU - Subramanian, G. Mani

AU - Symonds, William

AU - Mchutchison, John G.

AU - Mangia, Alessandra

AU - Gane, Edward

AU - Mizokami, Masashi

AU - Pol, Stanislas

AU - Afdhal, Nezam

PY - 2015/7/1

Y1 - 2015/7/1

N2 - Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon-free regimens of direct-acting antiviral agents, making it difficult to optimize therapy. We performed a post-hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed-dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment-naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV-SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease-inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%-98%) achieved SVR12, 98% of treatment-naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV-SOF alone and 97% of those who received LDV-SOF plus RBV), although previously treated patients receiving 12 weeks of LDV-SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV-SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%-19%), and asthenia (14%-16%). One patient (

AB - Patients with hepatitis C virus (HCV) infection and cirrhosis are underrepresented in clinical trials of interferon-free regimens of direct-acting antiviral agents, making it difficult to optimize therapy. We performed a post-hoc analysis of data from seven clinical trials to evaluate the efficacy and safety of the fixed-dose combination of ledipasvir (LDV) and sofosbuvir (SOF), with and without ribavirin (RBV), in 513 treatment-naïve and previously treated patients with genotype 1 HCV and compensated cirrhosis. All patients received LDV-SOF for 12 or 24 weeks with or without RBV. We determined the rates of sustained virological response (SVR) 12 weeks after treatment (SVR12) overall and for subgroups. Of the 513 patients analyzed, 69% were previously treated and 47% had failed previous treatment with a protease-inhibitor regimen. Overall, 493 patients (96%; 95% confidence interval [CI]: 94%-98%) achieved SVR12, 98% of treatment-naïve and 95% of previously treated patients. SVR12 rates did not vary greatly by treatment duration (95% of patients receiving 12 weeks and 98% of patients receiving 24 weeks of treatment), nor by addition of RBV (95% of patients receiving LDV-SOF alone and 97% of those who received LDV-SOF plus RBV), although previously treated patients receiving 12 weeks of LDV-SOF without RBV had an SVR12 rate of 90%. One patient discontinued LDV-SOF because of an adverse event (AE). The most common AEs were headache (23%), fatigue (16%-19%), and asthenia (14%-16%). One patient (

UR - http://www.scopus.com/inward/record.url?scp=84933181270&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84933181270&partnerID=8YFLogxK

U2 - 10.1002/hep.27826

DO - 10.1002/hep.27826

M3 - Article

C2 - 25846144

AN - SCOPUS:84933181270

VL - 62

SP - 79

EP - 86

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 1

ER -