Safety and Tolerability Of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection

Analysis of Phase III ION Trials

Saleh Ali Alqahtani, Nezam Afdhal, Stefan Zeuzem, Stuart C. Gordon, Alessandra Mangia, Paul Kwo, Michael Fried, Jenny C. Yang, Xiao Ding, Phillip S. Pang, John G. Mchutchison, David Pound, K. Rajender Reddy, Patrick Marcellin, Kris V. Kowdley, Mark Sulkowski

Research output: Contribution to journalArticle

Abstract

In phase III studies, treatment with the once-daily fixed-dose combination tablet of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV-SOF with and without RBV. We analyzed treatment-emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index ≥30 kg/m2, and 440 (23%) were treatment experienced. Treatment-related AEs occurred in 71% and 45% of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving RBV with LDV/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV/SOF alone. Rates of treatment-related serious AEs and discontinuations resulting from AEs were similarly low (

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalHepatology
Volume62
Issue number1
DOIs
StatePublished - Jul 1 2015

Fingerprint

Ribavirin
Chronic Hepatitis C
Hepacivirus
Genotype
Safety
Infection
Fibrosis
Therapeutics
Sleep Initiation and Maintenance Disorders
Pruritus
Exanthema
African Americans
Tablets
Fatigue
sofosbuvir drug combination ledipasvir
Body Mass Index

ASJC Scopus subject areas

  • Hepatology
  • Medicine(all)

Cite this

Safety and Tolerability Of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection : Analysis of Phase III ION Trials. / Alqahtani, Saleh Ali; Afdhal, Nezam; Zeuzem, Stefan; Gordon, Stuart C.; Mangia, Alessandra; Kwo, Paul; Fried, Michael; Yang, Jenny C.; Ding, Xiao; Pang, Phillip S.; Mchutchison, John G.; Pound, David; Reddy, K. Rajender; Marcellin, Patrick; Kowdley, Kris V.; Sulkowski, Mark.

In: Hepatology, Vol. 62, No. 1, 01.07.2015, p. 25-30.

Research output: Contribution to journalArticle

Alqahtani, SA, Afdhal, N, Zeuzem, S, Gordon, SC, Mangia, A, Kwo, P, Fried, M, Yang, JC, Ding, X, Pang, PS, Mchutchison, JG, Pound, D, Reddy, KR, Marcellin, P, Kowdley, KV & Sulkowski, M 2015, 'Safety and Tolerability Of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection: Analysis of Phase III ION Trials', Hepatology, vol. 62, no. 1, pp. 25-30. https://doi.org/10.1002/hep.27890
Alqahtani, Saleh Ali ; Afdhal, Nezam ; Zeuzem, Stefan ; Gordon, Stuart C. ; Mangia, Alessandra ; Kwo, Paul ; Fried, Michael ; Yang, Jenny C. ; Ding, Xiao ; Pang, Phillip S. ; Mchutchison, John G. ; Pound, David ; Reddy, K. Rajender ; Marcellin, Patrick ; Kowdley, Kris V. ; Sulkowski, Mark. / Safety and Tolerability Of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection : Analysis of Phase III ION Trials. In: Hepatology. 2015 ; Vol. 62, No. 1. pp. 25-30.
@article{768a3d85468447839a6ac57911558e79,
title = "Safety and Tolerability Of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection: Analysis of Phase III ION Trials",
abstract = "In phase III studies, treatment with the once-daily fixed-dose combination tablet of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV-SOF with and without RBV. We analyzed treatment-emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 received LDV/SOF alone) were analyzed. Overall, 308 patients (16{\%}) were African American, 224 (11{\%}) had compensated cirrhosis, 501 (26{\%}) had a body mass index ≥30 kg/m2, and 440 (23{\%}) were treatment experienced. Treatment-related AEs occurred in 71{\%} and 45{\%} of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving RBV with LDV/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV/SOF alone. Rates of treatment-related serious AEs and discontinuations resulting from AEs were similarly low (",
author = "Alqahtani, {Saleh Ali} and Nezam Afdhal and Stefan Zeuzem and Gordon, {Stuart C.} and Alessandra Mangia and Paul Kwo and Michael Fried and Yang, {Jenny C.} and Xiao Ding and Pang, {Phillip S.} and Mchutchison, {John G.} and David Pound and Reddy, {K. Rajender} and Patrick Marcellin and Kowdley, {Kris V.} and Mark Sulkowski",
year = "2015",
month = "7",
day = "1",
doi = "10.1002/hep.27890",
language = "English (US)",
volume = "62",
pages = "25--30",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - Safety and Tolerability Of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic Hepatitis C Virus Genotype 1 Infection

T2 - Analysis of Phase III ION Trials

AU - Alqahtani, Saleh Ali

AU - Afdhal, Nezam

AU - Zeuzem, Stefan

AU - Gordon, Stuart C.

AU - Mangia, Alessandra

AU - Kwo, Paul

AU - Fried, Michael

AU - Yang, Jenny C.

AU - Ding, Xiao

AU - Pang, Phillip S.

AU - Mchutchison, John G.

AU - Pound, David

AU - Reddy, K. Rajender

AU - Marcellin, Patrick

AU - Kowdley, Kris V.

AU - Sulkowski, Mark

PY - 2015/7/1

Y1 - 2015/7/1

N2 - In phase III studies, treatment with the once-daily fixed-dose combination tablet of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV-SOF with and without RBV. We analyzed treatment-emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index ≥30 kg/m2, and 440 (23%) were treatment experienced. Treatment-related AEs occurred in 71% and 45% of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving RBV with LDV/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV/SOF alone. Rates of treatment-related serious AEs and discontinuations resulting from AEs were similarly low (

AB - In phase III studies, treatment with the once-daily fixed-dose combination tablet of ledipasvir/sofosbuvir (LDV/SOF) with and without ribavirin (RBV) resulted in high rates of sustained virological response (SVR) in patients chronically infected with genotype 1 hepatitis C virus, including those with compensated cirrhosis. We conducted an analysis of data from these trials to compare the safety and tolerability profile of LDV-SOF with and without RBV. We analyzed treatment-emergent adverse events (AEs) and laboratory abnormalities in patients who were randomized to 8, 12, and 24 weeks of LDV/SOF with or without RBV. In total, data from 1,952 patients (of whom 872 received LDV/SOF with RBV and 1,080 received LDV/SOF alone) were analyzed. Overall, 308 patients (16%) were African American, 224 (11%) had compensated cirrhosis, 501 (26%) had a body mass index ≥30 kg/m2, and 440 (23%) were treatment experienced. Treatment-related AEs occurred in 71% and 45% of patients treated with and without RBV, respectively, including fatigue, insomnia, irritability, and rash/pruritus. Patients receiving RBV with LDV/SOF were more likely to require dose modification, interruptions of treatment resulting from AEs, or require the use of concomitant medications than those receiving LDV/SOF alone. Rates of treatment-related serious AEs and discontinuations resulting from AEs were similarly low (

UR - http://www.scopus.com/inward/record.url?scp=84933181408&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84933181408&partnerID=8YFLogxK

U2 - 10.1002/hep.27890

DO - 10.1002/hep.27890

M3 - Article

VL - 62

SP - 25

EP - 30

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 1

ER -