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Interferon‐free regimens containing setrobuvir for patients with genotype 1 chronic hepatitis C: a randomized, multicenter study
Author(s) -
Jensen Donald M.,
Brunda Michael,
Elston Robert,
Gane Edward J.,
George Jacob,
Glavini Katerina,
Hammond Janet M.,
Le Pogam Sophie,
Nájera Isabel,
Passe Sharon,
Piekarska Anna,
Rodriguez Ignacio,
Zeuzem Stefan,
Chu Tom
Publication year - 2016
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12997
Subject(s) - medicine , chronic hepatitis , genotype , multicenter study , randomized controlled trial , hepatitis c , interferon , gastroenterology , virology , biology , virus , gene , biochemistry
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 DAA s (setrobuvir, danoprevir/r, mericitabine) plus ribavirin for 12 weeks (Group A: G1a; D: G1b) or 24 weeks (B: G1a), and two groups received 2 DAA s (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, SVR 12). Results Two groups met predefined futility criteria for breakthrough (C) or relapse (A) and were discontinued. SVR 12 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 log 10 IU by the end of the lead‐in period ( n = 28) achieved SVR 12. 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 DAA s plus ribavirin) is safe and effective in treatment‐naïve G1 patients.