Safety of the 2D/3D direct-acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - A pooled analysis.

Abstract

BACKGROUND & AIMS:

Chronic hepatitis C virus (HCV)-infected patients with cirrhosis are a high-priority population for treatment. To help inform the benefit-risk profile of the all-oral direct-acting antiviral (DAA) combination regimen of ombitasvir, paritaprevir, and ritonavir, with or without dasabuvir (OBV/PTV/r±DSV) in patients with Child-Pugh A cirrhosis, we undertook a comprehensive review of AbbVie-sponsored clinical trials enrolling patients with Child-Pugh A cirrhosis.

METHODS:

Twelve phase II or III clinical trials of the 2-DAA regimen of OBV/PTV/r±ribavirin (RBV) or the 3-DAA regimen of OBV/PTV/r+DSV±RBV that included patients with Child-Pugh A cirrhosis were reviewed; patients who completed treatment by November 16, 2015 were included in a pooled, post hoc safety assessment. The number and percentage of patients with treatment-emergent adverse events (TEAEs), serious TEAEs, and TEAEs consistent with hepatic decompensation were reported.

RESULTS:

In 1,066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% confidence interval [CI]: 4.1-6.8) and 2.2% (95% CI: 1.4-3.2), respectively. Thirteen patients (1.2%; 95% CI: 0.7-2.1) had a TEAE that was consistent with hepatic decompensation. The most frequent TEAEs consistent with hepatic decompensation were ascites (n=8), esophageal variceal hemorrhage (n=4), and hepatic encephalopathy (n=2).

CONCLUSIONS:

This pooled analysis in 1,066 HCV-infected patients with Child-Pugh A cirrhosis confirms the safety of OBV/PTV/r±DSV±RBV in this population. These results support the use of OBV/PTV/r±DSV±RBV in this high-priority population. Lay summary: This pooled safety analysis in 1,066 HCV-infected patients with compensated cirrhosis, receiving treatment with ombitasvir, paritaprevir, and ritonavir with or without dasabuvir, with or without ribavirin, shows that the rate of hepatic decompensation events was similar to previously reported rates in untreated patients.

• Authors: Fred Poordad, David R Nelson, Jordan J Feld, Michael W Fried, Heiner Wedemeyer, Lois Larsen, Daniel E Cohen, Eric Cohen, Niloufar Mobashery, Fernando Tatsch, Graham R Foster
• Journal: Journal of hepatology (J Hepatol) Vol. 67 Issue 4 Pg. 700-707 (10 2017) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 28645740 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anilides
• Antiviral Agents
• Carbamates
• Cyclopropanes
• Lactams, Macrocyclic
• Macrocyclic Compounds
• Sulfonamides
• ombitasvir
• Ribavirin
• Uracil
• Proline
• 2-Naphthylamine
• dasabuvir
• Valine
• Ritonavir
• paritaprevir

Topics

• 2-Naphthylamine
• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Anilides (administration & dosage, adverse effects)
• Antiviral Agents (administration & dosage, adverse effects)
• Carbamates (administration & dosage, adverse effects)
• Clinical Trials, Phase II as Topic
• Clinical Trials, Phase III as Topic
• Cyclopropanes
• Drug Therapy, Combination
• Drug-Related Side Effects and Adverse Reactions (etiology)
• Female
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Lactams, Macrocyclic
• Liver Cirrhosis (drug therapy, etiology)
• Macrocyclic Compounds (administration & dosage, adverse effects)
• Male
• Middle Aged
• Proline (analogs & derivatives)
• Ribavirin (administration & dosage, adverse effects)
• Ritonavir (administration & dosage, adverse effects)
• Sulfonamides (administration & dosage, adverse effects)
• Sustained Virologic Response
• Uracil (administration & dosage, adverse effects, analogs & derivatives)
• Valine
• Young Adult