Gastroenterology. 2013 Nov 18. pii: S0016-5085(13)01653-3. doi: 10.1053/j.gastro.2013.11.007. [Epub ahead of print]
Gane EJ, Stedman CA, Hyland RH, Ding X, Svarovskaia E, Subramanian GM, Symonds WT, McHutchison JG, Pang PS.
New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand. Electronic address: edgane@adhb.govt.nz.
Abstract
BACKGROUND & AIMS: We evaluated an all-oral regimen comprising the nucleotide polymerase inhibitor sofosbuvir with the NS5A inhibitor ledipasvir or the NS5B non-nucleoside inhibitor GS-9669 in patients with genotype 1 hepatitis C virus (HCV) infection.
METHODS: A total of 113 patients were enrolled. Sofosbuvir (400 mg once daily) and ledipasvir (90 mg once daily) plus ribavirin were given for 12 weeks to treatment-naïve patients (n=25) and those who did not respond to previous therapy (prior null responders, n=9). Sofosbuvir and GS-9669 (500 mg once daily) plus ribavirin were given for 12 weeks to treatment-naïve patients (n=25) and prior null responders (n=10). Additionally, prior null responders with cirrhosis were randomly assigned to groups given a fixed-dose combination of sofosbuvir and ledipasvir, with ribavirin (n=9) or without ribavirin (n=10). Finally, a group of treatment-naïve patients received sofosbuvir, ledipasvir, and ribavirin for 6 weeks (n=25). The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12).
RESULTS: SVR12 was achieved by 25/25 (100%) of treatment-naïve patients receiving sofosbuvir, ledipasvir, and ribavirin and 23/25 (92%) of those receiving sofosbuvir, GS-9669, and ribavirin. Of treatment-naïve patients receiving 6 weeks of sofosbuvir, ledipasvir, and ribavirin, 17/25 (68%) achieved SVR12. All non-cirrhotic prior null responders receiving 12 weeks of sofosbuvir along with another direct-acting antiviral agent plus ribavirin achieved SVR12-9/9 (100%) of those receiving sofosbuvir, ledipasvir, and ribavirin and 10/10 (100%) of those receiving sofosbuvir, GS-9669, and ribavirin. Among cirrhotic prior null responders, SVR12 was achieved by 9 (100%) of those receiving sofosbuvir, ledipasvir, and ribavirin and 7 (70%) of those receiving sofosbuvir and ledipasvir without ribavirin. The most common reported adverse events were headache, fatigue, and nausea.
CONCLUSIONS: The combination of sofosbuvir and a second direct-acting antiviral agent is highly effective in treatment-naïve patients with HCV genotype 1 infection and in patients that did not respond to previous treatment.
CLINICALTRIALS.GOV NUMBER:
NCT01260350.
Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
KEYWORDS: DAA, HCV, LDV, RBV, SOF, SVR12, TN, clinical trial, drug, hepatitis C virus, ledipasvir, liver cirrhosis, ribavirin, sofosbuvir, sustained virologic response 12 weeks post therapy, treatment-naïve
PMID: 24262278 [PubMed - as supplied by publisher]
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