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

Journal of Hepatology - June 20, 2017
Articles in Press

DOI: http://dx.doi.org/10.1016/j.jhep.2017.06.011

Publication stage: In Press Accepted Manuscript

Published online: June 20, 2017

Safety of the 2D/3D direct acting antiviral regimen in HCV-induced Child-Pugh A cirrhosis - a pooled analysis
Fred Poordad Correspondence information about the author Fred Poordad Email the author 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

Highlights

• •OBV/PTV/r ± DSV ± RBV was well-tolerated in patients with Child-Pugh A cirrhosis.
• •Low rates of serious adverse events and those leading to discontinuation of study drugs.
• •Events consistent with hepatic decompensation occurred in 1.2% of patients (13/1066)
• •Decompensation events occurred across the treatment period and post-treatment.
• •Rates of decompensation events were comparable in treated and untreated patients.

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 1066 patients with Child-Pugh A cirrhosis, rates of serious TEAEs and TEAEs leading to study drug discontinuation were 5.3% (95% 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 1066 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 1066 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 comparable to rates from historical reports for untreated patients.