Long-term follow-up of clinical trial patients treated for chronic HCV infection with daclatasvir-based regimens

Liver Int. 2018 May;38(5):821-833. doi: 10.1111/liv.13596. Epub 2017 Oct 12.

Abstract

Background & aims: Daclatasvir has achieved high sustained virologic response (SVR) rates in diverse hepatitis C virus (HCV) populations. This study evaluated the long-term efficacy and safety of daclatasvir-based regimens administered during clinical studies.

Methods: Patients enrolled within 6 months of parent study completion or protocol availability at the study sites. The primary objective was durability of SVR at follow-up Week 12 (SVR12). Secondary objectives included analysing HCV sequences in non-responders or responders who relapsed, and characterization of liver disease progression.

Results: Between 24 February 2012 and 17 July 2015, this study enrolled and began following 1503 recipients of daclatasvir-based regimens (follow-up cut-off, 13 October 2015); 60% were male, 18% aged ≥65 years, 87% had genotype-1a (42%) or -1b (45%) infection, and 18% had cirrhosis. Median follow-up from parent study follow-up Week 12 was 111 (range, 11-246) weeks. 1329/1489 evaluable patients were SVR12 responders; 1316/1329 maintained SVR until their latest visit. Twelve responders relapsed by (n = 9) or after (n = 3) parent study follow-up Week 24; one was reinfected. Relapse occurred in 3/842 (0.4%) and 9/487 (2%) responders treated with interferon-free or interferon-containing regimens, respectively. Hepatic disease progression and new hepatocellular carcinoma were diagnosed in 15 and 23 patients, respectively. Among non-responders, emergent non-structural protein-5A (NS5A) and -3 (NS3) substitutions were replaced by wild-type sequences in 27/157 (17%) and 35/47 (74%) patients, respectively.

Conclusions: SVR12 was durable in 99% of recipients of daclatasvir-based regimens. Hepatic disease progression and new hepatocellular carcinoma were infrequent. Emergent NS5A substitutions persisted longer than NS3 substitutions among non-responders.

Trial registration: ClinicalTrials.gov NCT01492504.

Keywords: chronic hepatitis C virus; daclatasvir; hepatocellular carcinoma; long-term follow-up; sustained virologic response.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Carbamates
  • Disease Progression
  • Drug Resistance, Viral
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hepacivirus
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Humans
  • Imidazoles / therapeutic use*
  • Liver Cirrhosis / virology*
  • Male
  • Middle Aged
  • Pyrrolidines
  • RNA, Viral
  • Sustained Virologic Response
  • Valine / analogs & derivatives
  • Viral Load
  • Young Adult

Substances

  • Antiviral Agents
  • Carbamates
  • Imidazoles
  • Pyrrolidines
  • RNA, Viral
  • Valine
  • daclatasvir

Associated data

  • ClinicalTrials.gov/NCT01492504