The efficacy and safety of dual oral therapy with daclatasvir and asunaprevir for genotype 1b in Japanese real-life settings.

Abstract

BACKGROUND & AIMS:

It is important to investigate the treatment outcomes in patients excluded from clinical trials (CTR). The aims of this study were to evaluate the efficacy and safety of a 24-week daclatasvir (DCV) and asunaprevir (ASV) therapy for patients with chronic hepatitis C virus (HCV)-1b infection.

METHODS:

A total of 651 HCV-1b patients started dual oral therapy with DCV and ASV for 24 weeks in Toranomon Hospital, Tokyo. Among them, 276 patients met phase III CTR inclusion criteria. The sustained virological response (SVR) rate after treatment and the adverse events during therapy were compared between CTR-met (patients who met the inclusion criteria) and CTR-unmet (patients who did not meet the inclusion criteria) groups.

RESULTS:

SVR12 was achieved in 87.0% (240/276) and 86.7% (325/375) in CTR-met and CTR-unmet patients respectively. SVR12 rate in simeprevir-experienced patients was 52.9% (9/17). SVR12 rate in patients without resistance-associated variant (RAV) of NS3 or NS5A loci was 93.7% (416/444). However, the SVR12 rates in patients with NS3-D168, NS5A-L31 and Y93 single RAV at baseline were 55.0% (11/20), 73.9% (17/23) and 65.6% (63/96) respectively. The safety profiles in both CTR-met and CTR-unmet patients were similar. The discontinuation rate as a result of alanine aminotransferase (ALT) elevation was only 2.9%. Seven (2.5%) patients in CTR-met group and 20 (5.3%) in CTR-unmet group discontinued therapy because of adverse events other than the ALT elevation.

CONCLUSIONS:

Dual oral therapy with DCV and ASV in real-life settings was well tolerated with a similar safety profile and achieved similar SVR12 rates as that of CTR.

• Authors: Hitomi Sezaki, Fumitaka Suzuki, Tetsuya Hosaka, Norio Akuta, Shunichiro Fujiyama, Yusuke Kawamura, Masahiro Kobayashi, Yoshiyuki Suzuki, Satoshi Saitoh, Yasuji Arase, Kenji Ikeda, Mariko Kobayashi, Hiromitsu Kumada
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 37 Issue 9 Pg. 1325-1333 (09 2017) ISSN: 1478-3231 [Electronic] United States
• PMID: 28178397 (Publication Type: Clinical Trial, Phase III, Journal Article)
• Copyright: © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Carbamates
• Imidazoles
• Isoquinolines
• Pyrrolidines
• RNA, Viral
• Sulfonamides
• Viral Nonstructural Proteins
• Alanine Transaminase
• Valine
• daclatasvir
• asunaprevir

Topics

• Administration, Oral
• Aged
• Alanine Transaminase (blood)
• Antiviral Agents (administration & dosage, adverse effects)
• Carbamates
• Drug Resistance, Viral (genetics)
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (genetics)
• Hepatitis C, Chronic (drug therapy)
• Humans
• Imidazoles (administration & dosage, adverse effects)
• Isoquinolines (administration & dosage, adverse effects)
• Japan
• Logistic Models
• Male
• Middle Aged
• Pyrrolidines
• RNA, Viral (blood)
• Sulfonamides (administration & dosage, adverse effects)
• Sustained Virologic Response
• Valine (analogs & derivatives)
• Viral Nonstructural Proteins (genetics)