A 3-year follow-up study after treatment with simeprevir in combination with pegylated interferon-α and ribavirin for chronic hepatitis C virus infection.

Abstract

BACKGROUND:

Simeprevir is approved with pegylated interferon and ribavirin (PR) for chronic hepatitis C virus (HCV) genotype (GT) 1 and GT4 infection in the USA and the European Union.

METHODS:

This 3-year follow-up study assessed the durability of sustained virologic response (SVR) (undetectable HCV RNA 12 or 24 weeks after treatment end), and evaluated the persistence of treatment-emergent NS3/4A protease inhibitor resistance in patients not achieving SVR following treatment with simeprevir plus PR in the parent study. The maintenance of SVR after the last post-therapy follow-up visit of the parent study (LPVPS) was assessed using HCV RNA measurements. The persistence of treatment-emergent NS3 amino acid substitutions in patients with no SVR at LPVPS was assessed using population sequencing. No study medications were administered.

RESULTS:

Overall, 249 patients were enrolled (200 with SVR at LPVPS; 49 with no SVR at LPVPS); 40 patients discontinued prematurely (18 with SVR; 22 with no SVR). All 200 enrolled patients who achieved SVR in the parent study maintained SVR until the last available visit in this study (median follow-up time: 35.8 months). The treatment-emergent NS3 amino acid substitutions detected at time of failure in the parent study in 43/49 enrolled patients were no longer detected in 37/43 (86.0%) at the end of this study (median follow-up time: 179.9 weeks [41.3 months]).

CONCLUSION:

This 3-year follow-up study provides evidence for the long-term durability of SVR (100%) after successful treatment with simeprevir plus PR. Treatment-emergent NS3 amino acid substitutions became undetectable in the majority of patients.

TRIAL REGISTRATION:

NCT01349465; ClinicalTrials.gov .

• Authors: Fabien Zoulim, Christophe Moreno, Samuel S Lee, Peter Buggisch, Andrzej Horban, Eric Lawitz, Chris Corbett, Oliver Lenz, Bart Fevery, Thierry Verbinnen, Umesh Shukla, Wolfgang Jessner
• Journal: Virology journal (Virol J) Vol. 15 Issue 1 Pg. 26 (01 30 2018) ISSN: 1743-422X [Electronic] England
• PMID: 29378602 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Interferon-alpha
• Ribavirin
• Simeprevir

Topics

• Adult
• Aged
• Aged, 80 and over
• Antiviral Agents (pharmacology, therapeutic use)
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Follow-Up Studies
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (diagnosis, drug therapy, virology)
• Humans
• Interferon-alpha (pharmacology, therapeutic use)
• Male
• Middle Aged
• Mutation
• Ribavirin (pharmacology, therapeutic use)
• Simeprevir (pharmacology, therapeutic use)
• Sustained Virologic Response
• Treatment Outcome
• Viral Load