Daclatasvir plus asunaprevir for HCV genotype 1b infection in patients with or without compensated cirrhosis: a pooled analysis.

Abstract

BACKGROUND & AIMS:

We compared outcomes by cirrhosis status across studies of the all-oral combination of daclatasvir (DCV) plus asunaprevir (ASV).

METHODS:

Outcomes from global and Japanese phase 2 and 3 clinical studies of DCV+ASV in patients with genotype (GT) 1b infection were assessed by cirrhosis status. Sustained virological response (SVR) was assessed in individual phase 3 studies; a pooled analysis was carried out for safety outcomes.

RESULTS:

In the Japanese phase 3 study, SVR12 was achieved by 91% of patients with cirrhosis (n = 22) and 84% of patients without cirrhosis (n = 200); in the global phase 3 study, SVR12 was achieved by 84% of patients with cirrhosis (n = 206) and by 85% of patients without cirrhosis (n = 437). The frequency of serious adverse events, adverse events leading to treatment discontinuation and treatment-emergent grade 3/4 laboratory abnormalities was low (<10%) and similar among patients with (n = 229) or without (n = 689) compensated cirrhosis receiving DCV+ASV. Grade 3/4 reductions in platelets and neutrophils were more common among patients with cirrhosis (1.3 and 2.2%, respectively) compared with those without cirrhosis (both 0.6%). Grade 3/4 liver function test abnormalities were less common among patients with cirrhosis (1.8%) compared with those without cirrhosis (3.5-4.7%). Alanine aminotransferase elevations were not associated with hepatic decompensation.

CONCLUSIONS:

The safety and efficacy of DCV+ASV were similar in patients with or without compensated cirrhosis. This all-oral, interferon- and ribavirin-free combination is an effective and well-tolerated treatment option for patients with HCV GT1b infection and cirrhosis. Trial registrations numbers: Clinicaltrials.gov identifiers: NCT01012895; NCT01051414; NCT01581203; NCT01497834.

• Authors: Jia-Horng Kao, Donald M Jensen, Michael P Manns, Ira Jacobson, Hiromitsu Kumada, Joji Toyota, Jeong Heo, Boris Yoffe, William Sievert, Fernando Bessone, Cheng-Yuan Peng, Stuart K Roberts, Youn-Jae Lee, Rafia Bhore, Patricia Mendez, Eric Hughes, Stephanie Noviello
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 36 Issue 7 Pg. 954-62 (07 2016) ISSN: 1478-3231 [Electronic] United States
• PMID: 26683763 (Publication Type: Clinical Trial, Phase II, Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Isoquinolines
• Pyrrolidines
• Sulfonamides
• Alanine Transaminase
• Valine
• daclatasvir
• asunaprevir

Topics

• Alanine Transaminase (blood)
• Antiviral Agents (administration & dosage, adverse effects)
• Carbamates
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Hepacivirus (genetics)
• Hepatitis C, Chronic (complications, drug therapy)
• Humans
• Imidazoles (administration & dosage, adverse effects)
• International Cooperation
• Isoquinolines (administration & dosage, adverse effects)
• Liver (physiopathology)
• Liver Cirrhosis (epidemiology)
• Male
• Middle Aged
• Pyrrolidines
• Sulfonamides (administration & dosage, adverse effects)
• Sustained Virologic Response
• Valine (analogs & derivatives)