Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort

Gut. 2016 Nov;65(11):1861-1870. doi: 10.1136/gutjnl-2016-312444. Epub 2016 Sep 7.

Abstract

Objective: We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease.

Design: Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians' discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12).

Results: Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child-Pugh B/C; 46% Model for End-Stage Liver Disease score >10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI -2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related.

Conclusions: DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease.

Trial registration number: NCT02097966.

Keywords: ANTIVIRAL THERAPY; CHRONIC VIRAL HEPATITIS; CIRRHOSIS; HEPATITIS C.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / administration & dosage
  • Antiviral Agents / adverse effects
  • Carbamates
  • Cohort Studies
  • Compassionate Use Trials
  • Drug Monitoring / methods
  • Drug Therapy, Combination / methods
  • Europa
  • Female
  • Hepacivirus* / drug effects
  • Hepacivirus* / genetics
  • Hepatitis C, Chronic* / complications
  • Hepatitis C, Chronic* / diagnosis
  • Hepatitis C, Chronic* / drug therapy
  • Humans
  • Imidazoles* / administration & dosage
  • Imidazoles* / adverse effects
  • Liver Failure* / complications
  • Liver Failure* / diagnosis
  • Male
  • Middle Aged
  • Pyrrolidines
  • Ribavirin* / administration & dosage
  • Ribavirin* / adverse effects
  • Severity of Illness Index
  • Sofosbuvir* / administration & dosage
  • Sofosbuvir* / adverse effects
  • Treatment Outcome
  • Valine / analogs & derivatives

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • Ribavirin
  • Valine
  • daclatasvir
  • Sofosbuvir

Associated data

  • ClinicalTrials.gov/NCT02097966
  • ClinicalTrials.gov/NCT02097966