Interferon-free regimens containing setrobuvir for patients with genotype 1 chronic hepatitis C: a randomized, multicenter study.

Autor: Jensen DM; University of Chicago Medicine, Chicago, IL, USA., Brunda M; Roche Innovation Center, New York, NY, USA., Elston R; Roche Products Ltd, Welwyn, UK., Gane EJ; Auckland Clinical Studies, Grafton, New Zealand., George J; Storr Liver Unit, Westmead Hospital and University of Sydney, Westmead, NSW, Australia., Glavini K; Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland., Hammond JM; Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland., Le Pogam S; Genentech, South San Francisco, CA, USA., Nájera I; Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland., Passe S; Roche Innovation Center, New York, NY, USA., Piekarska A; Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź, Poland., Rodriguez I; Roche Innovation Center, New York, NY, USA., Zeuzem S; Medizinische Klinik I, Johann-Wolfgang-Goethe University Hospital, Frankfurt, Germany., Chu T; Roche Innovation Center, New York, NY, USA.
Jazyk: angličtina
Zdroj: Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2016 Apr; Vol. 36 (4), pp. 505-14. Date of Electronic Publication: 2015 Dec 12.
DOI: 10.1111/liv.12997
Abstrakt: Background & Aims: Setrobuvir is a direct-acting antiviral (DAA) non-nucleoside inhibitor of hepatitis C virus (HCV) polymerase. This study examined interferon-free combinations containing setrobuvir, a ritonavir-boosted protease inhibitor (danoprevir/r) and ribavirin, with/without the nucleoside inhibitor mericitabine in HCV genotype (G)1 patients.
Methods: Non-cirrhotic treatment-naïve patients (N = 110) were randomized to five groups. Three groups received a 14-day mericitabine/ribavirin lead-in followed by treatment with 3 DAAs (setrobuvir, danoprevir/r, mericitabine) plus ribavirin for 12 weeks (Group A: G1a; D: G1b) or 24 weeks (B: G1a), and two groups received 2 DAAs (setrobuvir, danoprevir/r) plus ribavirin for 12 weeks (E: G1b) or 24 weeks (C: G1a). Efficacy was defined as sustained virological response (HCV RNA <25 IU/ml after 12 weeks' follow-up, SVR12).
Results: Two groups met predefined futility criteria for breakthrough (C) or relapse (A) and were discontinued. SVR12 rates were 42.9% (3/7) and 74.1% (20/27) in G1a patients in Groups A and B, respectively, and 95.7% (22/23) and 68.2% (15/22) in G1b patients in Groups D and E respectively. All G1a patients assigned to 24 weeks of treatment who experienced a decrease in HCV RNA of ≥2.3 log10 IU by the end of the lead-in period (n = 28) achieved SVR12. Overall, treatment was well tolerated and most adverse events were mild to moderate. No major safety signals were identified.
Conclusions: An interferon-free setrobuvir-based regimen (3 DAAs plus ribavirin) is safe and effective in treatment-naïve G1 patients.
(© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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