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 MD^13,*

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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