March 10, 2014

Daclatasvir plus asunaprevir for chronic HCV genotype 1b infection

Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

Viral Hepatitis

Hiromitsu Kumada MD1, Yoshiyuki Suzuki MD1, Kenji Ikeda MD1, Joji Toyota MD2, Yoshiyasu Karino MD2, Kazuaki Chayama MD3, Yoshiiku Kawakami MD3, Akio Ido MD4, Kazuhide Yamamoto MD5, Koichi Takaguchi MD6, Namiki Izumi MD7, Kazuhiko Koike MD8, Tetsuo Takehara MD9, Norifumi Kawada MD10, Michio Sata MD11, Hidetaka Miyagoshi12, Timothy Eley PhD13, Fiona McPhee PhD13, Andrew Damokosh PhD13, Hiroki Ishikawa12, Eric Hughes MD13,*

DOI: 10.1002/hep.27113

Copyright © 2014 American Association for the Study of Liver Diseasews

Publication History
Accepted manuscript online: 6 MAR 2014 06:10AM EST
Manuscript Accepted: 28 FEB 2014
Manuscript Revised: 21 FEB 2014
Manuscript Received: 10 FEB 2014

Keywords: Direct-acting antiviral; nonresponder; interferon-ineligible; interferon-intolerant; all-oral

Abstract

All-oral combinations of direct-acting antivirals may improve efficacy and safety outcomes for patients with hepatitis C virus (HCV) infection, particularly those who are poor candidates for current interferon/ribavirin-based regimens. In this open-label, phase 3 study, 135 interferon-ineligible/intolerant and 87 nonresponder patients with chronic HCV genotype 1b infection were enrolled at 24 centers in Japan. Patients received daclatasvir 60 mg once daily plus asunaprevir 100 mg twice daily for 24 weeks. The primary end point was sustained virologic response 24 weeks after treatment (SVR24). This study is registered with ClinicalTrials.gov (NCT01497834). SVR24 was achieved by 87.4% of interferon-ineligible/intolerant patients and 80.5% of nonresponder (null and partial) patients; rates were similar in cirrhotic (90.9%) and non-cirrhotic (84.0%) patients, and in patients with IL28B CC (84.5%) or non-CC (84.8%) genotypes. Fourteen patients in each group (12.6%) discontinued dual therapy, mainly due to adverse events or lack of efficacy. Nine nonresponder patients received additional treatment with peginterferon/ribavirin per protocol-defined criteria. The rate of serious adverse events was low (5.9%) and varied among patients. The most common adverse events were nasopharyngitis, increased ALT and AST, headache, diarrhea, and pyrexia.

Conclusion: Interferon-free, ribavirin-free all oral therapy with daclatasvir and asunaprevir for 24 weeks is well tolerated and can achieve a high rate of SVR in patients with HCV genotype 1b who were ineligible, intolerant, or had not responded to prior interferon-based therapy. (Hepatology 2014;)

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