Daclatasvir plus simeprevir with or without ribavirin for the treatment of chronic hepatitis C virus genotype 1 infection

JOURNAL OF HEPATOLOGY

卷:64

Article

Zeuzem, Stefan¹  Hezode, Christophe²  Bronowicki, Jean-Pierre³  Loustaud-Ratti, Veronique⁴  Gea, Francisco⁵  Buti, Maria^6,7  Olveira, Antonio⁵  Banyai, Tivadar⁸  Al-Assi, M. Tarek⁹  Petersen, Joerg¹⁰  Thabut, Dominique¹¹  Gadano, Adrian¹²  Pruitt, Ronald¹³  Makara, Mihaly¹⁴  Bourliere, Marc¹⁵  Pol, Stanislas¹⁶  Beumont-Mauviel, Maria¹⁷  Ouwerkerk-Mahadevan, Sivi¹⁸  Picchio, Gaston¹⁹  Bifano, Marc²⁰  McPhee, Fiona²¹  Boparai, Navdeep²⁰  Cheung, Kin²¹  Hughes, Eric A.²⁰  Noviello, Stephanie²⁰ 

[1] Klinikum Goethe Univ, D-60590 Frankfurt, Germany

[2] Univ Paris Est, Hop Henri Mondor, AP HP, INSERM U955, Creteil, France

[3] Univ Lorraine, Ctr Hosp Univ Nancy, INSERM U954, Vandoeuvre Les Nancy, France

[4] Univ Limoges, CHU Limoges, INSERM U850, F-87000 Limoges, France

[5] Hosp Univ La Paz, Madrid, Spain

[6] Hosp Valle De Hebron, Barcelona, Spain

[7] Inst Salud Carlos III, CIBEREHD, Madrid, Spain

[8] Pandy Kalman Hosp, Gyula, Hungary

[9] Texas Digest Dis Consultants, Arlington, TX USA

[10] IFI Inst Interdisziplinare Med, Hamburg, Germany

[11] Hop La Pitie Salpetriere, Paris, France

[12] Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina

[13] Nashville Med Res Inst, Nashville, TN USA

[14] St Laszlo Hosp, Budapest, Hungary

[15] Hop St Joseph, Marseilles, France

[16] Univ Paris 05, Hop Cochin, AP HP, Unite Hepatol,INSERM UMS 20,Inst Pasteur, Paris, France

[17] Janssen Infect Dis BVBA, Beerse, Belgium

[18] Janssen Res & Dev, Beerse, Belgium

[19] Janssen Res & Dev, Titusville, NJ USA

[20] Bristol Myers Squibb Co, Res & Dev, Princeton, NJ USA

[21] Bristol Myers Squibb Co, Res & Dev, Wallingford, CT 06492 USA

关键词: Hepatitis C virus;    Genotype 1;    Direct-acting antiviral;    All-oral therapy;    Daclatasvir;    NS5A inhibitor;    Simeprevir;    NS3 protease inhibitor;   

DOI  :  10.1016/j.jhep.2015.09.024

来源: Elsevier

【 摘 要 】

Background & Aims: We evaluated the combination of daclatasvir (pan-genotypic NS5A inhibitor) and simeprevir (NS3/4A protease inhibitor), with or without ribavirin, in hepatitis C virus genotype 1-infected patients. Methods: This phase II, open-label study enrolled treatment-naive patients or prior null responders with genotype 1b (n = 147) or 1a (n = 21) infection. Genotype 1b-infected patients were randomized 1:1 to receive daclatasvir 30 mg plus simeprevir 150 mg once daily with or without ribavirin; those who completed the initial 12-week treatment were re-randomized 1:1 to stop treatment or continue treatment through to week 24. Genotype 1a-infected patients received daclatasvir plus simeprevir with ribavirin for 24 weeks. The primary endpoint was the proportion of patients with sustained virologic response at posttreatment week 12 (SVR12). Results: For genotype 1b, 84.9% (45/53) and 74.5% (38/51) of treatment-naive patients and 69.6% (16/23) and 95.0% (19/20) of prior null responders to peginterferon and ribavirin achieved SVR12 with daclatasvir plus simeprevir alone and with ribavirin, respectively. Treatment duration did not have a well-defined impact on response. For genotype 1a, daclatasvir plus simeprevir with ribavirin provided a 66.7% (8/12) response rate in treatment-naive patients and was not effective in prior null responders. Data suggest that baseline resistance polymorphisms influenced SVR12 rates. Daclatasvir plus simeprevir was well tolerated with or without ribavirin with low incidences of serious adverse events and adverse events leading to discontinuation. Conclusions: Daclatasvir plus simeprevir, with or without ribavirin, was effective with a 12- or 24-week duration in genotype 1b-infected patients and was well tolerated. (C) 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

【 授权许可】

Free