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

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.

• Authors: K Rajender Reddy, Stanislas Pol, Paul J Thuluvath, Hiromitsu Kumada, Joji Toyota, Kazuaki Chayama, James Levin, Eric J Lawitz, Adrian Gadano, Wayne Ghesquiere, Guido Gerken, Maurizia R Brunetto, Cheng-Yuan Peng, Marcelo Silva, Simone I Strasser, Jeong Heo, Fiona McPhee, Zhaohui Liu, Rong Yang, Misti Linaberry, Stephanie Noviello
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 38 Issue 5 Pg. 821-833 (05 2018) ISSN: 1478-3231 [Electronic] United States
• PMID: 28941023 (Publication Type: Journal Article, Multicenter Study, Observational Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2017 The Authors. Liver International Published by John Wiley & Sons Ltd.

Chemical References

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

Topics

• Adult
• Aged
• Antiviral Agents (therapeutic use)
• Carbamates
• Disease Progression
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Hepacivirus
• Hepatitis C, Chronic (complications, 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