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

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

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12 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)954-962
Number of pages9
JournalLiver International
Volume36
Issue number7
DOIs
Publication statusPublished - 2016

Keywords

  • cirrhosis
  • direct acting antiviral
  • hepatitis C
  • safety

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