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

UNLABELLED:

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/m(2) , 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 (<1%) in both groups. The rate of SVR in those receiving RBV and those not receiving RBV was the same (97%).

CONCLUSION:

LDV/SOF plus RBV was associated with a greater incidence of AEs as well as concomitant medication use than LDV/SOF alone. Use of RBV did not impact the efficacy of LDV/SOF regimens in the ION phase III studies.

• Authors: Saleh A 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
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 62 Issue 1 Pg. 25-30 (Jul 2015) ISSN: 1527-3350 [Electronic] United States
• PMID: 25963890 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2015 by the American Association for the Study of Liver Diseases.

Chemical References

• Antiviral Agents
• Benzimidazoles
• Fluorenes
• ledipasvir, sofosbuvir drug combination
• Ribavirin
• Uridine Monophosphate
• Sofosbuvir

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (therapeutic use)
• Benzimidazoles (therapeutic use)
• Drug Therapy, Combination
• Female
• Fluorenes (therapeutic use)
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (complications, drug therapy, virology)
• Humans
• Liver Cirrhosis (virology)
• Male
• Middle Aged
• Ribavirin (therapeutic use)
• Sofosbuvir
• Uridine Monophosphate (analogs & derivatives, therapeutic use)
• Young Adult